Unit 2 Study GuideChapter 8- The Central Nervous System

• CNS comprised of brain & spinal cord– functions to:

• receive input from sensory neurons• direct activity of motor neurons that innervate muscles & glands• association, or interneurons within brain & spinal cord serve to “associate” appropriate motor

responses with sensory stimuli, thus maintaining homeostasis• during development

– CNS forms from a long tube– anterior portion becomes brain, folds during formation, with different regions becoming apparent

• retains “hollow” morphology with cavities called ventricles• filled with cerebrospinal fluid

• CNS comprised of gray & white matter– brain

• 3-3.5 lbs• receives ~15% of total bld flow to body per min

• high metabolic requirements• brain

– involvement in learning & memory, permits behavior to be modified by experience• benefits survival

– along with perceptions, emotions & perhaps self-awareness forms basis of consciousness– contains about 100 billion neurons– total length of “wires” = 100,000 miles– neural stem cells

• develop into neurons and glial cells• neurogenesis

• subventricular zone • subgranular zone

– brain creations--not a “singular event”

Cerebrum• largest portion of brain• region primarily responsible for higher brain functions• divided into left & right hemispheres

– connected internally via large fiber tract• corpus callosum

• comprised of 5 lobes– Table 8.1 - functions

• cerebral cortex– outer layer of cerebrum

• 2-4 mm thick• gray matter

– anatomic construction increases area for neurons but does not increase volume • gyrus/gyri & sulcus/sulci

– most complex integrating area of Nervous System • cortex is mapped to regions of body - somatotopy

– Point by point correspondence between body area and Central Nervous System– note that body part size does not correspond with amt of cortical area used

• Highest receptor densities represent largest areas of sensory cortex• Greater number of motor innervations represent largest motor cortical area• Ex. The lips have more cortical area than the trunk even though the legs have more area.

• What is involved with facial expression has more cortical area than larger body movements• Lips are more sensitive than trunk–

– (front of central sulcus) Motor – skeletal muscle movements– (back of central sulcus) Somatosensory- general sensation – Facial expression use smaller motor units; trunk use larger motor units- gross movements– Finer movement= more cortical area; mass movement= less cortical area– It looks at more receptor number, finer movements

Electroencephalogram• synaptic potentials produced by cell bodies & dendrites in cerebral cortex create electrical currents that can be

measured by electrodes placed on the scalp– EEG– Looking at change in membrane potentials and action potentials via EEG– Brain activity – wavelike pattern

• used clinically to diagnose epilepsy & other abnormal states– Epilepsy abnormal synchronized discharges of cerebral neuron– electrical storm within a short circuit, occurs at small spot within brain – focus – causes waves of

electrical activity to spread throughout brain– Epilepsy electrical storm in a short circuit; the focus starts waves of activity spreading throughout the

brain (seizure) – huge spikes in the wave • Small area in brain (focus) causes waves throughout the brain that overrides everything• Did not breath, couldn’t speak, no control over mobile abilities • Degree and magnitude of the spikes tell clinicians different things about the grade of the

seizure. • Can cause brain damage.

• absence of EEG signifies brain death• Types of Waves

– Alpha waves– typically for parietal, occipital lobes; what you see in awake adult with eyes closed and relaxed

– Beta– frontal lobe; “evoked activity” produced when there is visual and mental activity– Theta- temporal and occipital lobes; sleeping adults; you see it in newborns

• If seen in an awake adult– several emotional distress and forewarn for a nervous breakdown– Delta- cerebral cortex, normal and dominant common in infants and sleeping adults

• If seen in adult that’s awake signify brain damage

Sleep • Function unknown—but it is a homeostatic requirement and responsible for the consolidation of memories from

short term to long term– Sleep is dangerous in the wild because you will be susceptible to danger. It must have some purpose if

willing to put at risk to sleep. • EEG patterns change with sleep

– REM sleep—dreams• Rapid eye movement sleep • heart rate, respiration rate and number of eye movements increase during REM sleep (but neck

muscle movements decrease during REM)• non-REM (NREM) sleep

– remainder of time during sleep (spend most of your time here) – resting sleep- physiological maintanence

• observe cycles with subject going through stages of NREM sleep, then ascend back through to REM, followed by stages of NREM

– cycle = ~90 mins ( stages 14, REM, 41)– 4-5 cycles per night– typically wake up from REM sleep-- you don’t go through all the stages when you get closer to waking

• Glymphatic system– mental janitor, maintance of physiological process of the brain – variety of things get flushed out

– Get rid of waste and unneeded proteins/ GUNK– Lymphatic system not present in Nervous system; network of channels that allow for movement and

clearing of toxins through cerebral spinal fluid regulated by glial cells – glymphatic system!– Parallel to lymphatic system but in the brain – Interstitial spaces During sleep the compartment increased from 14%-20% volume and can reach

further into the brain; when you allow sleep to occur you can flush waste products 2x faster than if you keep them awake all the time.

– Something there to increase volume there during sleep to sweep out things • In general, important to get sleep and especially prior to an exam because it helps with memorue (you want to

use long term memory for an exam).

Basal/Cerebral Nuclei• masses of gray matter deep within white matter of cerebrum• play important role in movement & posture as well as complex aspects of behavior• prominent basal nuclei

– corpus striatum: 3 nuclei structures in brain contains the motor circuit• caudate & lentiform (putamen & globus pallidus) nuclei• motor circuit—allows intended movements while inhibiting unintended movements that can

interfere with the intended movement1. motor cortex sends excitatory signals to basal nuclei2. putamen in Basal Nuclei, sends inhibitory signals to other Basal Nuclei areas3. Globus pallidus and Substantia Nigra send inhibitory signals to thalamus4. thalamus then sends excitatory signals to motor cortex

• substantia nigra & subthalamic nuclei– functionally associated with basal nuclei

• Motor Circuit Summary– motor cortex sends excitatory signals to basal nuclei– putamen in BN, sends inhibitory signals to other BN areas– GP and SN send inhibitory signals to thalamus– thalamus then sends excitatory signals to motor cortex

• Parkinson’s disease loss of dopamine leads to Parkinson’s and the substantia nigra influences Parkinson’s

Cerebral/Hemispheric Lateralization• cerebral hemispheres appear symmetrical, but each has anatomic, chemical & functional specializations• info entering brain decussates (crosses over) thus right side of brain controls left side of body

– Communication between both hemispheres via corpus callosum keeps each hemisphere appraised of “total” body function

– Decussation occurs in the medulla• through experimentation, found that each hemisphere is good at certain categories of tasks and poor at others

– lead to concept of cerebral dominance• Analogous to handedness

– right-handed, left hemisphere dominant– hemispheres function complementary to each other (neither subordinate)

• Doesn’t mean that the left hemisphere doesn’t over power right– but if your right handed there is more activity on the left side of brain.

– observe specialization of function in one hemisphere • cerebral lateralization

• speculate that creative ability may be related to interaction of information between hemisphere– left side is good for language and analytical ability– right side is good for visuospatial ability– EX. Right is good at recognizing the face but left is good at interpreting the face

• Left handed—more bihemispheric and more gifted in athletics and gaming – If you are creative or artistic you have better communication between the two hemispheres--- tending

to be left handed– Some of the artists can write and draw with both their right and left hands

Language• Language is a complex code that includes the acts of listening, seeing, reading and speaking with each aspect of

language dealt with by different regions– knowledge gained through study of aphasias - speech & language disorders, caused by damage to the

brain through injury or stroke• Wernicke’s area– understanding written and spoken language

– Concept of words originates in this region – Damage to this area the individual will provide a “word salad” they can fluently speak but you can’t

understand what they are saying– also have difficulty to understand written or spoken area – Fluent speech but incomprehensible, difficulty understanding spoken and written language

• Broca area- direct muscles with speech and preparation to speak (only in one hemisphere) • Potential for development of language specific mechanisms in left hemisphere is present at birth, yet

assignment is flexible in early years of life; after, success rate declines– Injury or accident in a young person – language can be reassigned. Once you reach puberty it starts to

decrease--The success rate of reassigning language is lower after puberty.

PET Scans• Increased blood flow (bright colors) to specific lobes of brain during various language-based activities• Hear words – warnicke’s area is red areas• Seeing words- vision location• Speaking words – brocas area, motor areas• Generation words- everywhere especially prefrontal lobe • The full cerebrum is involved with language activities

Limbic System & Emotion• Hypothalamus & limbic system are important brain region for neural element of emotional states• Involves in : aggression, fear, feeding, goal-oriented behavior (reward/punishment system) & sexual

behavior/drive o It’s very hard to control emotion

• Includes amygdala, hippocampus, fornex, septum, etc. • Papez circuit—closed circuit that info flows through between limbic system, thalamus and hypothalamus

o Involved in moving short term memories to long term (consolidation of memories pass through circuit)o Connection of neurons through the hypothalamus and limbic system o Aka hippocampal/mamillothalamic tract

• Limbic system center of emotional drives and derived early in course of vertebrae evolutiono Observe few synaptic connections between cerebral cortex & limbic system structures which is why we

have little control over emotions• Memories with an emotional component are easier to remember but if it is too traumatic you don’t remember it

Learning• acquisition and storage of info as a consequence of experience

– measured by increase in likelihood of particular behavioral response to a stimulus– If you pick up a pot you put it down really quickly because you don’t want to be burned– rewards/punishments crucial ingredients in learning (training a dog)

Memory• relatively permanent storage form of learned information

– not single, unitary phenomenon

• brain processes, stores & retrieves info in different ways to suit different needs• several different brain regions involved with storage & retrieval

– amnesia - - loss of memory• result with damage to several different areas– can be combinations or a single area that wipes

out certain types of memory• suggests the presence of several different systems of info storage available in brain – learned

from accidents that cause amnesia• to make memories permanent you need to move through the pez circuit• different categories:

– short-term, or working memory• registers & retains incoming information for a short time

– retention – seconds to minutes• new memories not instantly permanent & susceptible to modification (can be modified easily)

– Why there is an accident you are asked by police officer to ask questions– you modify accident as time progresses.

– require protein synthesis before becoming stable (we need to run through prepez circuit• stored differently dependent on type of information to be stored

– involves prefrontal lobe– long-term memory

• store for days to years• depends on the synthesis of mRNA & protein• memory consolidation

– conversion of short-term memories, recalled at a later time• classified as:

– nondeclarative, or implicit memory• memory of a simple skills & conditions

– declarative, or explicit memory• retention and recall of conscious experiences that can be put into words• sematic (fact) & episodic (event) memory

• Event memory- what you are felling at the time when you recall memories

• Sematic- memories when you do daily activities (naming a structure)• hippocampus appears to be an impt component of memory system• emotions influence & strengthen/hinder memory formation

– amygdala – improves memory when there is an emotional content (fear)• fear can make a memory strong and can also hinder recovery

– hardest memories to remember- trauma—blocks memory – memories that are clear are typically POSITIVE emotion

• stress hinders memory formation– reduces ability of hippocampus to form memories

• mechanism unknown but area targeted (hippocampus & amygdala) due to presence of Receptors for stress Hormones

• synaptic changes occurs when consolidating memories – short-term memory involves establishment of recurrent/reverberating circuits

• reverberating circuit—input from one end, a lot of collaterals coming off of axons and the signal keeps moving along the circuit until you run out of NT

– need synaptic changes for consolidation to occur– consolidation involves permanent changes to the chemical structure of neurons & their synapses with

protein synthesis being required• LTP-long-term potentiation

– type of synaptic learning– mech couples frequent activity across synapse with lasting changes in signal strength

across the synapse

– induces dendritic spines to enlarge and change shape • LTP PROCESS

– 1. high frequency action potential come to synapse release secretory vesicles contain glutamate

– 2. bind too the receptor AMPA and the NNDA (2 receptors)– 3. AMPA opens channel and sodium and potassium to move causing depolarization

– Long Term Potentiation• Low frequency action

potentials = LTP• Two different receptors- they

are BOTH needed (AMPA & NMDA receptors)

• Second receptor NMDA requires two elements to open

– Binding of glutamate. – At least a 20-30 mV

depolarizing event – Magnesium ion is

kicked off and opens gate and calcium flows through… To activate 2nd

messenger to occur. – High frequency

important to initiate because we need depolarization

• We generating retrograde – nitrogen oxide & post synaptically we see in increase in glutamate sensitivity (2nd messenger system)

• NO promotes LTP by amount of glutamate released • Depolarization-induced suprresion of inhibition endocannabinoids

– Endocannabinoids- block GABAs effect from other presynaptic neurons- we block the inhibition that come from collateral

• Decreasing GABA released • Blocking so we don’t inhibit pathway

• LTP dendrites enlarge and change shape• Lower calcium levels leads to activation of phosphatases that dephosphorylate AMPA recpetors,

also observe a decrease in AMPA receptor numbers • neural stem cells

– found in hippocampus– suggest that neurogenesis may be involved in learning & memory

• we may be laying down new neurons to store memory • we can reset- if you don’t ue it you lose iit – limited capacity and rewrite them • if you haven’t used a pathway for a while there will be lower calcium levels which activated

phosphatase the AMPA receptors to take them away Diencephalon

• represents structures around 3rd ventricle & are completely surrounded by the cerebral hemispheres• comprised of:

– thalamus• primarily relay center through which all sensory info passes to cerebrum

• Thalamus is relay center for all sensory info coming from entire body (post office...sort likes together and ship off to appropriate areas). Olfactory, smell is the only sense that does not go through thalamus.

– epithalamus• pineal gland

– hypothalamus• collection of nuclei that are involved in a variety of homeostatic processes• Hypothalamus- homeostatic control center, autonomic nervous system, influence blood

pressure, heart rate, emotions, thermostat, circadian rhythm, etc. Brainstem

• comprised of midbrain, pons & medulla• injury here is very hard to fix• involve rigidly, programmed automatic behaviors necessary for survival as well as providing a pathway for fiber

tracts running between higher & lower neural centers– not a lot of flexibility – expressway for information

• midbrain– cerebral peduncles (ascending/descending fiber tracts)

• visual- track with movement or eyes across field• auditory- startle reflex (try to track the noise)

– corpora quadrigemina (visual/auditory reflexes) tectal plate – red nucleus (motor coordination)– substantia nigra (movement, mood, reward, addiction) motor circuit

• lose of neurons leads to Parkinson’s• pons - modifies

– passage of sensory & motor tracts– several nuclei associated with CNs– observe autonomic respiratory centers

• associate with medulla to regulate breathing• medulla - sets

– all ascending & descending tracts between spinal cord & brain pass through this region• site of decussation

– sets rate and depth of breathing – nuclei impt for motor control– house vital centers

• Grouping of neurons required for regulation of breathing and cardiovascular responseCerebellum (little brain)

• An absolute for motor learning and coordination – Without the cerebellum you would be unable to coordinate time and force for movements

• second largest structure of brain• receives input from proprioceptors & works together with basal nuclei & cerebral cortex motor areas in

coordination of movement– proprioceptors- degree of flexion within joint, joint stretching

• needed for motor learning & coordinating movement of different joints in movement• required for proper timing and force required for limb movements• current research suggest may have other functions besides motor

– Schizophrenia• Hard time organizing thoughts• individual interprets reality abnormally• cognitive dysmetria

– General discoordination of sensorimotor and mental processes– Autism

• group of developmental problems, affect child’s ability to communicate & interact with others

• smaller/abnormal areas in vermis• Ataxia—damage to the cerebellum

– Lack of muscle coordination during voluntary (skeletal muscle) movementsReticular Formation and RAS

• an interconnected group of neurons that constitutes an arousal system– not found in one given structure but found in a region of the brain stem (have neurons throughout

cerebrum as well)– reticular activating system (not concrete, theory)

• promotes wakefulness when activated and sleep when inhibited– accomplished via use of excitatory & inhibitory NTs

» work in tandem, like a switch• many drugs act on the RAS, promoting sleep or wakefulness• narcolepsy

– LHA neuron loss» release polypeptide NTs that promote arousal» Varying degrees

• Hypothesis for sleep wake cycles– During waking, aminergic neurons dominate

• General Monoamines released (serotonin and norepinephrine)• Decrease in acetylcholine release

– during REM sleep, cholinergic neurons are domain• increase in acetylcholine • decrease in serotonin and norepinephrine

– Hypothalamic neurons project to RAS and influence sleep-wake cycles in regards to biological clock aligned with circadian rhythm

– Restfulness- neurons from hypothalamus influence biological clock• Activation of this system decrease histamine and increase GABA• Benadryl make you drowsy it is an antihistamine blocking histamine allowing GABA to dominant

and brain will move toward nonREM sleep

Spinal Cord Tract & Cranial/Spinal NervesWhat type of information do ascending tracts carry? How about descending tracts?

• Ascending tract – sensory; from sensory receptors into cerebrum• Descending tract—motor; out of cerebrum into skeletal muscle

Do all nerve fibers decussate in the medulla? Can you explain how a person with lesions in the left hemisphere often have impaired motor activity in both hands?

• Not all fibers decussate in medulla some also decussate in spinal cord or some don’t decussate at all • Left hemisphere controls right side, however, can indirectly control left hand through projection neurons

through corpus callosum. (allow for cross talk between right and left hemisphere)• Left hemisphere specialized for skilled motor activity for both hands • Would you anticipate as much of an effect if lesions in right hemisphere? NO, bc left hand side has skilled motor

activity center- you see more effect on left side damage Look at Figure 8.26, pp 235 - Does initiation of a skeletal muscle event involve just activation of the motor area of the cerebral cortex? Explain.

• NO, there are other structures that play a role (basal and cerebral nuclei, cerebellum, midbrain nuclei)• Motor circuit

Define what is meant by peripheral nervous system.• PNS is any nervous tissue outside CNS (brain and spinal cord) represented by nerves (cranial and spinal)

Using Figure 8.28, pp 238, diagram the neural pathway of a reflex arc & describe the function of each component. Is the brain directly involved with the body’s response to sensory stimulation?

• Always start with sensor- sensory receptor• Afferent/sensory neuron• Integration center—interneuron

• Efferent/motor neuron• Effector—skeletal muscle • The brain is NOT directly involved in reflex – it runs without involving brain but it is made aware of reflex

Questions to ponder1. Summarize the players in the overall process to coordinate body movement

– primary motor cortex, cerebral/basal nuclei, midbrain nuclei (substantia nigra), cerebellum 2. Compare and contrast Broca’s aphasia with Wernicke’s aphasia

– difficulties speaking but their comprehensions of speech may be unaffected—Broca’s– rapid, fluid speech without meaning – Wernicke’s

3. When standing with your eyes closed, why do you sway more than when your eyes are open but do not lose your balance and fall over?

– balance is due to not only vestibular apparatus but also visions and proprioception (tell you when your joints are straight and bent- to tell where your body is in space)

4. Describe the components of the hypothalamic-pituitary-adrenal gland axis.– Part of GAS– Long-term responses to stress

5. Describe the difference between a general sensation, such as a free nerve ending, and a special sense, such as gustation, physiologically speaking.

– Asking you about a sensory system: sensory receptor, neural pathway and brain area. – Free nerve ending—widely distributed

• Sensory receptor on end of afferent neuron, then sensory pathway to cerebral cortex- somatosensory region

– Gustatory/taste cell—localized, head • Receptor cell to afferent neuron, then sensory pathway to cerebral cortex- specific regions

Chapter 9 – Autonomic Nervous System • Autonomic Nervous System Neurons

– Innervate organs whose functions typically not under voluntary control– Unlike somatic, have a 2 neuron pathway

• Preganglionic neuron that synapses with postganglionic neuron which makes contact with effector neuron

• Somatic motor pathway (one neuron to skeletal muscle)

•

– autonomic ctrl integral part of organ systems physiology – common features:

• resting tone (tension) in absence of nerve stimulation• denervation hypersensitivity

– autonomic nerve damage results in an target tissue sensitivity to stimulating agents (damage to a motor neuron leads to paralysis)

» a compensatory event to nerve damage (very adventous)• autonomic innervation

– target tissues display autorhythmicity» autorhythmicity- beat without innervation » organs “independent” of their innervation» modulator NOT an initiator that we see with somatic motor innervation » EX. Pacemaker cells in heart causing contraction of Autonomic nervous system

can increase rhythm or slow it down – or target tissue activity

Divisions of the Autonomic Nervous System • ANS– two neuron pathway • Parasympathetic– stem from cranial nerves and sacral region of spinal cord

– Also called Craniosacral– “brake” Slows things down – “rest and digest” Activated after resting – Help to restore energy that has been utilized– Very directed and localized– Ganglia are housed on the target

organ – Preganglionic neuron is long and

postganglionic neuron is short• Sympathetic- arises from thoracic and

lumbar region of spinal cord– “gas”—fight or flight– Speed things up (get ready to fight or

flight) – Activation of skeletal muscle– Pull energy from storage to – Preganglionic neuron is short and

long postganglionic neuron that innervates the organ

– Sympathetic chain that many of them synapse on

– Some organs are dual innervated by parasympathetic and sympathetic. (if only innervated by one it will be innervated by sympathetic

– Mass activation activation of many things at one time

• Speeding up heart rate• Activation if skeletal muscles • Quick mental thoughts

– A lot of red branches and connections; • TABLE 9.4 • Ganglion– collection of cell bodies in PNS

Neurotransmitters• All preganglionic neurons in Autonomic NS release

Acetylcholine** • Cholingeric transmission– utilization of acetylcholine• Post ganglionic neuron– the parasympathetic uses

acetylcholine • Sympathetic– adrenergic transmission utilizes norephrine

and epinephrine; amenergic – Amenergic- releases monoamines – Adrenergic- part of amenergic family but

specifically epinephrine and noepinephrine• ANS target is cardiac, smooth, and gland • Synapses en passant– synapses in passing; ARE NOT at the axonal terminals…enlargements/swellings called

varicosity on axons – Found in both sympathetic and parasympathetic

• Varicosity– found in sympathetic and parasympathetic; within them are Neurotransmitters; come close to target cell that have receptors for neurotransmitter – defuse type of synapse (

• Antagonistic effects organ is dual innervated one NT causes contraction and the other causes relaxation

Adrenergic Stimulation• response of target tissue dependent on R displayed

– α- & β-adrenergic Rs• subtypes

– act via G-proteins• Table 9.5• Clinical Application

– drugs can be agonists or antagonists• use of drugs that specifically stimulate/block various Rs can be used clinically to treat disease

– propranolol- developed for hypertension (high blood pressure) but can cause asthmatic effects

» Nonselective Beta-blocker in lungs can cause constriction in bronchioles (help blood pressure) and difficulty breathing

- PS– preganglionic release achetylcholine and bind to nicotinic receptors on post ganglionic cell (use muscarinic receptors)

- Sympathetic release ach and nicotoine- Use epinephrine and

norepinephrine (post ganglionic neuron)

- Use drugs to stimulate (agonist) or block receptors (antagonist) to treat diseases

» Needs to become a more elective drug (beta blocker 1 or 2 is blocked or some will block the actual pathway)

•

Cholinergic Stimulation

• preganglionic release is always excitatory (always release acetylcholine and bind to Nicotinic receptors ), postganglionic release can be either excitatory or inhibitory (muscarinic Ach)

– response is R type-dependent• subtypes

– Table 9.6– G- Protein linked that influence potassium channels (one opens and one closes– Inhibitory by opening potassium channels- hyperpolarization; excitatory by closing potassium channels-

depolarization• Other autonomic neurotransmitters, referred to as nonadrenergic, noncholinergic fibers—don’t release

epinephrine, norepinephrine, Ach (ATP, nitric oxide and VIP- Vasointestine peptide, a neurotransmitter that can be used by neurons in GI tract)

Organs with Dual Innervation• innervated by both PNS & SNS• not all organs are dual innervated• action:

– antagonistic• most common• one stimulates and another inhibits • ex. Parasympathetic is break and sympathetic is gas (always exceptions

– complementary• stimulation of either division causes similar effects • Salivary gland

» Becomes dry when you are asked to speak (nervousness)—viscous fluid• Sympathetic- vasoconstriction = thicker saliva

» Becomes watery/when you see food– cooperative

• stimulation cause different effects by PNS & SNS that work together to promote a single action» working together for a common good

• Ex. Male reproductive system – erection (parasympathetic) and ejaculation (Sympathetic)– point and shoot

Organs without Dual Innervation• Usually sympathetic NS- interact by increasing and decreasing firing rate

– ANS-- modification• include:

– adrenal gland, arrector pili muscle, sweat glands & most blood vessels• regulation achieved by or in tone (firing rate) of SNS fibers

Control of Autonomic Nervous System by Higher Brain Centers• visceral functions regulated by autonomic reflexes, as sensory input to brain centers integrate & respond by

modifying preganglionic neuron activity• neural centers of medulla control ANS activity

– ANS -- modification– responsive to hypothalamus, ie. higher brain center

• “major” regulatory center for ANS– Ex. Vasocreceptors that sense blood pressure are sent to hypothalamus and then to medulla

• limbic system– visceral response to emotional states (butterfly's when you’re nervous, blushing, becoming pale, cold

sweat) • Cerebellum movement, motion sickness, naseua, vomiting (response when not happy), dizziness,

cardiovascular changes, sweating• Medulla responds to hypothalamus• Hierarchy = hypothalamus (moderator between brain and medulla) > medulla

Chapter 10- Sensory Physiology• Neural mechanisms which process sensory info bringing awareness of internal and external environment • Sensory input is crucial for our interactions with environment around us and maintenance of homeostasis• Sensory system involves sensory receptor, neural pathway and brain

o Receptor neural pathway brain• Sensation– you becoming aware of sensory info coming in • Perception– putting an understanding of sensory information (a meaning to info coming in• Transduction– process by which sensory receptors take a stimulus (light, temperature) and convert it to stimulus

energy to something we understand (conversion to action potential or electrical activities on neurons)

Sensory Receptor Characteristics• each sensory R responds to a particular modality of environmental stimulus• major function is transduction -- transduces stimulus E into electrochemical E• brain interprets impulses along a specific neural pathway as the stimulus• Muller’s law it doesn’t matter what receptor is activated bc each nerve endings when stimulated gives rise to

on stimulation – Sensation depends on the part of the brain the neurons terminate not what is stimulated to begin with – Anywhere along pathway you will have sensation no matter what part is stimulated.

• Each sensory nerve ending, however stimulated, gives rise to its own specific sensation, moreover, each sensation type depends not on the nerve it travels but upon the part of the brain in which the fibers terminate

• sensory unit- part of sensory system– single afferent neuron & all its R endings– receptive field- are stimulated, activates a particular afferent neuron

• Receptors field- peripheral terminals that have receptors to whatever stimulus; activate area then activates a particular afferent neurons

• Overlap can be a problem– modality & body location (Modality—form of stimulus; temperature, light, pain)

• unique pathway• specific region of sensory cortex

– acuity, or precision• locate & discern one stimulus from another

– Stimulus location is coded by site of stimulate receptor (ie. Receptor to certain place in brain)

• amount of neuronal input convergence– Greater convergence, less acuity – What happens if its 20 neurons using the same pathway…convergence, losing acuity

Factors Affecting Acuity• Acuity = precision, ability to sense • Size of receptive field covered by a sensory unit impacts acuity

o Smaller receptive field- more sensitive• Sensory unit density and amount of overlap

o Larger density of receptive field more sensitive o Lips are more sensitive because they have many (greater number)

of smaller receptive field = higher density • Greater sensory neuron response when stimulus applied to center of

receptive field because there is a greater density of sensory receptors in the middle than on the sides

• Want to be able to distinguish two point contact

Lateral Inhibition • Most important mechanism enabling localization of stimulus site• Receptors at edge of stimulus strongly inhibited compared to center• Sensory neuron most strongly stimulated inhibits neighboring sensory

neurons• Lateral inhibition– find where the stimulus is occurring and originate from • Neuron in the center will be stimulated the most. Collaterals effect lateral

neurons are inhibited • lateral inhibition sharpens perception • The one that is greatly stimulated is the neuron it the signal is flowing

through but the ones next to it are inhibited (can be activated by stimuli but the collateral neurons and interneuron inhibit them via lateral inhibition)

Categories of Sensory Receptors• Structural

– simple (free nerve ending) or complex (rod & cone) in design– peripheral nerve ending free or encapsulated (Meissner’s corpuscle- connective tissue with fluid around

sensory dendrite)• Functional

– characterized by type of stimulus they respond do• chemoR- respond to chemicals• photoR• thermoR – respond to heat and temperature• mechanoR – respond to distortion (mechanical stress)• Nociceptor– respond to pain

– type of stimulus info delivered• Proprioceptors- take information from joints and tendons• cutaneous Receptors- take information from integument (cutaneous membrane/skin

• Exteroceptor—stimulus comes from outside the body– EX. Meissner’s corpuscle: registers touch

• Interoceptor – stimulus comes from inside the body – EX. Barror receptor in arteries: senses blood pressure

Sensory Adaptation • tonic Receptor

– maintain firing frequency during application of stimulus– Once stimulus is applied, Action potential are generated and then stopped when stimulus is withdrawn–

tonic R (what we often think of) • Slow adaption• Pain receptors are tonic– it does not go away because it can cause damage

• phasic Receptor– respond with quick burst of activity when stimulus 1st applied, then firing rate decreases

• Adaptation- the decrease in firing rate– quick short burst of impulses when stimulus applied, then another quick short burst of impulses when

stimulus removed• “on-off” info

– fast adapting; respond to initial stimulus in a BURST of activity and then firing rate decreases called adaptation

• However if stimulus changes the frequency changes – EX. When you get used to a smell

• Can’t feel your underwear, earrings, watch (when stimulus is constant you begin to ignore it- only realize when stimulus changes)

– Alert to change in stimulus, ignore constant stimulus. – Quick Burst when stimuli is applied than adapt (set and monitors) when stimulus change, frequency

changes and then a burst of impulse when removed! “On off”

Receptor (Generator) Potential • in response to stimulus, sensory endings produce local graded changes in membrane potential

– depolarizations• analogous to EPSPs (excitatory post synaptic potentials)

• the stronger the stimulus the greater the depolarization (we need to reach threshold to generate action potentials)

• Sensory Receptor Types– Ending of afferent neuron: Free nerve ending– the

receptor membrane is at the END of the afferent neuron– Cell adjacent to afferent neuron: Rods cones, taste cells or

those senses (receptor cell that has receptor membrane that response to stimulus and then releases NT to activate the sensory cell)

• Pacinian corpuscle- deep pressure and vibration (connective tissue layers surrounded by fluid)

– Phasic receptor– it will respond and then undergo adaption

– But then remove the capsule it will be free nerve endings and become tonic receptors

Response of Tonic Receptors • The generator potential is proportional to the intensity of the stimulus• If threshold is reached, an increase in the generator potential amplitude will result in an increase in action

potential frequency• As stimulus increases in size so does the generator potential closer to threshold• The frequency of the action potential is coded by the strength of the stimulus• Greater the stimulus the higher the frequency of action potential

Cutaneous Sensations• Result due to information from a variety of sensory receptors • There are different temperature receptors

– Cold receptors are closer to the surface (more superficial) than hot receptors • Somatic sensations—any kind of sensation from skin, muscles, bones, tendons and joints• Somatesthetic senses all the sensesations together; conscious awareness of body--- total body sensation from

all the somatic receptors

Gustation—Taste • Chemical sense—chemo receptors—exteroceptor • Found on dorsal surface of tongue• Taste bud – sensory structure • Chemo receptors are on hairs at the tip of the gustatory taste cell • Info from taste flow on cranial nerve 7 (facial) and nerve 9 (pharengeal) • Each taste has distinct signal transduction pathway• 5 tastes: sweet, sour, salty, bitter and unami

– Salty: sensory receptors and sodium channels cause depolarization and open calcium channels and then stimulate release of NT and signal moves to sensory neuron

– Sour: Hydrogen ions flow in channels and cause depolarization open calcium channels, release NT for that taste

» Gprotein pathways used by sweet (bind sugars) and unami (aged cheese, responds to aspartate and glutamate- amino acids) taste sensation pathway

» Gusducians: the g proteins » Activate second messengers » We CLOSE potassium channels causing a depolarizing affect and a release of NT – different

pathway » Artificial sweeteners taste more sweet than real sweeteners (natural sugar) because they take a

different pathway or different second messenger system – Bitter is the most acute sensation (responds to quinine)

» WHY? Many toxins taste bitter and bind to these receptors» G proteins release second messenger system » Released of calcium from endoplasmic reticulum and then causing the NT to release and the

sensory neuron is stimulated

•

Olfaction• Chemical sense—chemo receptor – exteroceptor • Food and odorants have to be dissolved in a fluid– mouth its saliva & Nasal cavity – mucus. • Dry food doesn’t have much taste until you get saliva on it. • When you are in a dry environment you can’t smell.. But moist like in a gym there are a lot of odors you pick up. • Sensory receptor is Bipolar neurons– few places in the body that a neuron is replaced. • Olfactorary epithelium– superior portion of the nasal cavity. • Have cilia where receptors are found• Odorant binds to receptor • G-proteins are bound to the receptor activate (alpha subunit) producing cAMP– activated by cyclase • Opening a sodium calcium channel– leading to depolarization

• Olfaction does NOT go through the thalamus because it goes from bipolar cells into glomeruli proceeded and moved through olfactory tract to the brain.

• Interestingly, genes for about 300 different olfactory receptor proteins with 1 receptor type expressed per bipolar neuron yet we can ID over 10,000 different odors

– Compared to other organism on this planet we have a poor sense of smell • Brain must somehow integrate info from many different R inputs and then interpret the pattern as a

characteristic– Your brain integrates the combinations of receptors that are activated- some are super smellers and

able to smell things at a better degree. – Combination of receptors integrate smells – Processing start in glomeruli info in and shared in the olfactory bulb then into the olfactory tract.

Vestibular Apparatus & Equilibrium • Sense of equilibrium provides orientation with respect to gravity due to function of the vestibular apparatus • Semicircular channels, vestibule --- vestibular apparatus• Fluid area with fluid sacs in skull • 2 fluids (inside and outside sacs)

– Perilymph--- extracellular fluid very similar to cerebral spinal fluid

– Endolymph- found within the membranous labyrinth; an extracellular fluid; but has very high potassium levels (higher than what you find within the cell intracellular fluid)

» Potassium higher extracellularly than intracellularly

» Lower in sodium and calcium• Hair bundle serve as receptors for equilibrium,

modified epithelial cells – When straight up we have a level of action

potential (frequency at rest) – Steriocillia away kinocilium – inhibitory signal- action potential frequency decrease– Steriocillia toward kinocilium – stimulated (depression in membrane) action potential increase in

frequency– Sensory cells in fluid environment as you move the fluid moves too! As fluid moves the cilia move in one

direction

Equilibrium• Ability to look at change in one direction• Macula found in utricle and sacral- linear acceleration• Utricle– horizontal movement• Sacral- vertical movement • rotational and angular acceleration semicircular canals- crista ampullaris

– Hair cells and gelatinous structure (cupulla) as fluids flow the cupulla moves one direction • Neural pathway involved with equilibrium and balance• Maintaining balance and equilibrium involves eyes, proprioceptor (joint,tendons and tendons), cerebellum and

vestibular nuclei– Vestibular nuclei take in sensory input coordinate motor activities

Ears and Hearing• Olfaction, gustation, hearing, equilibrium and vision– special cells

– Receptor cells that brings info into sensory neuron and then takes it on to neuron pathway • Outer ear (pinna/oracle)-- sound wave collection device and funnel them into external auditory canal• Sound waves hit tympanic membrane vibrates…Ear drum and moves from outer ear to middle ear• Middle ear (carved out portion of temporal bone)

– Mallus, Incus and stapes (3 ear bones) held by mini synovial joints, smallest bones in body, have tiny ligaments attached; AMPLIFY sound 20x

– Stapes up against the oval window--- pounds on scalae vestibulae (follow it around and open at the end)• Inner ear– sensory organs for hearing – cochlea

– Vibrates move through ossicles (ear bones) develop pressure waves with in the structures in the cochlea• Auditory tube – open into throat, starts in the middle ear and pushes through the inner ear

– Ears “pop” because equalizing pressure from middle ear into auditory tube

• Cochlear duct is where we find out sense organ (filled with endolymph- unique in that it is high in potassium)

– Filled with perilymph• Observe muscles in middle ear that contract when

sound is too loud—protective, due to dampens movements of ossicles (muscles cut down on amplification)

– Tempani muscle inserts on malleus– Stabidus muscle– insert on stapes – When sound gets loud the skeletal

muscles contract to dampen the amplification – don’t want to shear off the hair cells

• How Sounds travels– Unwind the cochlea – Stapes pound on oval window and waves flow through becoming pressure waves– Pressure waves have a frequency. How do you distinguish frequencies? – Basilar membrane bottom part of the cochlea – vibrates to determine frequency – Each sound frequency produced vibrations at a different region of the basilar membrane – Farthest away from oval window– low frequency– Closest to the oval window – high frequency– Pitch discrimination: depends on where the vibrations hit basilar membrane; Know the pitch because of

the location it is sent to within the cerebrum

Cochlea• Organ for hearing is the spiral organ of Corti (organ inside cochlear duct)

o Endolymph in cochlear duct o Perilymph in Scala tympani and scala vestibule & around the spiral organ

• Spiral organ is made of hair cells o Basilar membrane – vibrates to determine frequency o Steriocillia are in contact with tectorial membrane

• As basiliar membrane vibrates steriocillia bend and influence the tectorial membrane initiating neural pathway to hear

• Hair cells: Mechanisms for NT release o The steriocillia have tip links and when those links are stretched, we open potassium channels

(mechanically gated) causing depolarization event within hair cells voltage gated calcium channels which releases NT– activating afferent neurons

o Hair links are stacked: it is shut down o As you have vibrates you open and close the mechanically gated potassium channels

• endolymph is higher in potassium than sodium and calcium • Hair cells are refereed to inner and outer group

o Inner group are the sensory receptors and send on signalso Outer group serve as cochlear amplified for low sounds and soft sounds (built in amplifer)

• If you have a greater receptor potential it leads to greater action potentials- we code loudness by action potential frequencies because if we have more NT we get more action potential

o Denote loudnes greater displacement of basilar membrane, greater amount of NT released, leading to a greater receptor potential produced in afferent neuron

• Movement is due to the vibrations of basilar membrane

Eyes & Vision• Vision is Dominant sense • Anterior chamber– anything before the lens (between cornea and lens); aqueous humor (fluid)• Posterior chamber– behind lens; vitreous humor (jelly- more solid than aqueous humor)• Lining the inner surface of the eyeball is the retina --- sensory organ for vision location • Humans have limited range of vast vision spectrum (visible light)• Light starts in air—cornea—aqueous humor---lens--- vitreous humor--- retina • Eyes transduce energy in electromagnetic radiation into nerve impulses • Light passes from a medium of one density to a medium of a different density & is bent, or refracted• Cornea is constant and so is aqueous and vitreous humor (however changes with age)• Lens (not constant)can be modified to make sure light is centered onto retina• Fovea centralis– area of greatest visual acuity • Ganglion cells– form the optic nerve by collecting and exiting eye• Blind spot area where the vision exit • Light is bent, or refracted as it passes through the eye

o Light refraction is the mechanism which allows us to focus an image on retina• Lens is housed in a capsule with ligaments • Ciliary muscles around lens contract or contract to pull on dispensary ligaments and change the shape to the

lenso cornea curvature is constant BUT can adjust lens curvature therefore refractive properties of lens can

provide fine control for focusing light• Ability to keep image focused on retina as the distance between eyes and object varies is termed

accommodation, results from ciliary muscle contraction o As u see someone coming towards you and away u should stay focused on object that is changing

distance due to ciliary muscles activity• Some people have issues such as farsightedness can be corrected by external lens

o farsightedness-hyperopia– focus behind retina, need a convex lens to correct it

o nearsightedness-myopia– focus before the retina, need a concave lens to correct it Retina

• How do we see? Photoreceptor cells within in cells• Retina’s most distal portion Pigment epithelial– photoreceptor cells– bipolar cells– ganglion cells before the rods

and cones!• Light also need to pass through all the layers until it comes into outer cones• The outer segment of rods and cones contain the discs that contain photo pigment to sense light. • Retina is single layer of pigment epithelium, photoreceptor cells, and all the other neurons that are found• Photoreceptors bipolar ganglion cells

o Horizontal cells interneurons that assist with cones o Amacrine cells interneurons (helper cells) help the ganglion cells that help process info coming from

photoreceptor cells o Ganglion cells are the ones that carry the info ono Ganglion and amacrine cells produce action potential

• Close functional relationship between pigment epithelium and photoreceptor cells cells of pigment epithelium provide nutrients for photoreceptor cells, phagocytose shed outer segment, absorb scattered light, stabilize environment (ion composition), participate in visual cycle of retinol , suppress immune attack

o Retina is an immunologically privileged site• Rods (dim light, peripheral vision)• Cones( color, bright light)

• Effect of Light on Rods

• Photoreceptor cells activated when light produced chemical change in the disc’s pigment molecules• Rhodopsin—photoreceptor pigment made of opsin and retinal • Light causes components to dissociate• Retinol 11-cis confirmation when light hits rhodopsin changes to all trans; this slight change dissociates from

opsin and is called bleaching reaction– - light hits rhodopsin, retinal changes form and dissociates from 11 cis to all trans and activates opsin

• Photoreceptor cells release All trans retinal and taken up in to pigment epithelium converted back to 11 cis and given back to photoreceptor cells

• Visual cycle of retinal—interaction between photoreceptor cell and pigment epithelium—all trans retinal transported to Pigmented epithelium which converts it back to 11-cis

o When light hits and retinal dissociates, opsin activates transducen (Gprotein) and then activates phosphodiesterase which converts cGMP to GMP

o Importance? You can see by turning things OFFo Gynanyl cyclase- GTP converted to cGMP

cGMP binding to ion channels allowing NA and Ca to flow into cell: unique sensory cell that is depolarized at rest; with adequate stimulus, hyperpolarization occurs

In the dark we have dark current because we have cGMP open ion channels to allow Na and calcium to move into cell to depolarize

• all the free cGMP is broke to GMP and once all the GMP is broken the GMP is pulled off from the ion channels closing them! Then the cell hyperpolarizes – the signal (we turn it off in order to see)

•Effect of Light on Retinal Cells

• In the dark – sodium calcium channels open due to presence of cGMP - - - Depolarization—rod releases inhibitory NT to stop the process

• When light is present– activation of opsin by taking away cGMP and the channels are going to close (dark current stops) cell will hyperpolarize and no inhibitory NT is released but the bipolar cell releases excitatory NT (glutamate) to stimulate ganglion cells – signal moves on

• You see by turning things off. • as a light-adapted person enters a dark room,

temporarily “blinded”, dark adaptation, or the restoring of visual pigment in rods, must occur before they can “see” again

• in contrast, as a person steps from a dark place into bright sunlight, the image they see is too bright & of poor contrast, light adaptation occurs as rhodopsin in rods is bleached by light and cones become prominent operators, with a less bright image

• Give and take scenario • See color best in the light where cones are

primary operators • NOTE only ganglion cells and amacrine cells can

generate action potentials

Visual Acuity & Sensitivity • Fovea centralis represents an area of greatest visual

acuity; where the lens are designed to focus light• Exclusively made of cones, Rods off to the side but

mostly cones• Rods maximize sensitivity to low levels of light at

expense of visual acuity because they can convergence

o 5 rods that flow to one ganglion cell there is convergence

• Cones provide high visual acuity, but reduced sensitivity to light—no convergence

o You need to see color when light is bright because there is no convergence

o Directly from cone to bipolar cell to ganglion cell NO convergence

• Rod help when its dark when light is not available (don’t see sharp images)

• in the light when you see color– cones (can denote sharp images)

Chapter11 – Endocrine System/ Secretion & Action of Hormones• Endocrine glands are ductless glands which secrete their product, biologically active molecules called hormones,

into interstitial fluid and travel via blood/lymph to their target cells (contain receptors) that contain receptor proteins for a given hormone

– Endocrine is slower, Nervous is faster• Endocrinopathalies- dysfunctions of endocrine glands

– Diabetes mellitus- lack of insulin– Hyperthyroidism--- thyroid produces too much thyroid hormones– Cushing’s disease– excess of cortisol (Adrenal glands) moonface– Gigantism- over production of growth hormone in youth

Major Endocrine Glands• discrete organs

– Cardiovascular system or GI system is all connected. NOT the case in endocrine organ– primary function production/ secretion of hormones

• do NOT display the anatomical continuity typical of most other organ systems– widely scattered about the body– They are not continuous– widely spread throughout the body – Ovary, testis, pituitary, thymus, adrenal gland, pancreas, thyroid– not in one line

– comprised of endocrine cells (most of them)• glandular (epithelial) secretory cells – cells that secrete something

– Hypothalamus is also part of the nervous system– role in both sides • Homeostatic control center• Communicate between the two systems– neuroendocrine organ

– Adrenal medulla produced norepinephrine (NT) – different depending on what organ system produced it– Heart, GI tract, adipose tissue, skin affected by hormones

• Are these the only glands/ organs that secrete hormones in the human body?– no, observe nonendocrine organs with endocrine function

• heart, adipose tissue, GI tract, integument– hormones affect the metabolism of their target organs

– hormones mechanism of action deals with cellular metabolism• change some activity within the cell (Table 11.1)

Chemical Classification of Hormones• Hormones vary in their chemical structure• Grouped into chemical classes: amino acid derivatives, peptide derivatives and lipid derivatives

• Group by chemical classes and how an endocrinologist would• amino acid derivatives- small molecules derived from tyrosin or trypotophan

o norepinephrine, epinephrine (catecholamines) -- tyrosineo thyroid hormones- tyrosinso Melatonin (pineal gland) – trypotophan

• Peptide hormones- chains of AA o Can be small proteins, large, short o Majority of hormones fall into category (just about anything from this category)o Can by glycoproteins– with glucose attached

• Lipid derivatives– steroids (derived from cholesterol) o eicosanoids (biologically active lipids– arachidonic acid) – prostaglandins, thromboxanes

Hormone Synthesis• amino acid- based hormones often produced in an inactive, or precursor form known as prohormone• prehormone prohormone precursor • enzymes cleave prohormone into active phone• synthesis from a prohormone or a preprohormone perspective

o enzymes found in packaging, in the cell or where they are stored; even at the site of influence there can be a conversion of hormone

• enzymatic cleavage --. Hormone synthesis• POMC—pro-opiomelanocortin

o Depending on enzyme present in cells (different hormones in different cells mean different products) can get lipotrophin, Melanocyte stimulating hormone, LIP, endorphins

o A variety of hormones from one starting molecule- depends on how it’s clipped and the enzymes that do the clipping.

Common Aspects of Neural & Endocrine Regulation • NS & ES (controlling systems) work together to regulate and maintain body homeostasis (controlling systems)

– Nervous system is just a fast solution while endocrine is a more long lasting solution and modifies homeostasis

– action is complementary– similarities between two systems:

• rely on release of chemicals (hormones/ NT)• share chemical messengers (epinephrine)• regulated primarily by negative feedback mechanisms• share common goal – homeostasis

» by coordinating & regulating activities of cells, tissues, organs & organ systems and eventually the whole organism

– regulatory molecule to function in physiological regulation• target cells contain receptor that combines/binds with regulatory molecule• Hormone-receptor complex causes a cellular effect

» Once regulatory molecule binds to receptor something in the cell changes• mechanism to “turn off” regulator action (need a turn off switch)

• regulatory molecules discovered in unicellular organisms, suggest they appeared early in evolution & incorporated into Nervous and Endocrine systems

– not used in the same way but as organisms changed they were incorporated into various systems

Hormone Interactions• H effects can be complex, especially when you have multiple hormones acting on the same target cell

– Usually there is not one hormone acting at one time but multiple hormones that act on the same target cell

– Hormones may antagonize each other or work together to produce effects that are additive or complementary

• types of hormone interaction:– permissiveness—enhancing responsiveness/increase activity

• situation where one H acts to enhance the responsiveness of a target organ to a second H or increase the activity of the second H

• Thyroid hormones are notorious ( tissues won’t respond to a hormone unless thyroid is seen first)

– Synergism—two or more hormones work together• situation where two or more Hs work together to produce a particular result

– additive or complementary• Additive Glucagon and Epinephrine cause the liver to release glucose but if

you have both TOGETHER they will have 150% of effects than if they were singularly used

• Complementary lactation in the mammary glands (need several hormones lactin, oxytocin, estrogen to have milk production and secretion)

– Antagonism – oppose each other• situation where one H opposes the action of another H• Insulin and glucagon

– Insulin brings blood glucose levels down and glucagon brings blood glucose levels up

Effect of Hormone Concentration on Tissue Response• Hormones are only made as needed NOT stored (the case for many)—do not sit there waiting to be used• blood Hormone concentration reflects rate of secretion

– Hormones do not generally accumulate in blood• rapidly removed after binding to target tissue & removed by tissue or liver

• Hormone half-life– time required for the plasma concentration of a given amount of H to be reduced to half its reference

level (what it should be)• ranges from mins to hours for most Hormones—depends on the hormone type

• Hormone concentration impacts function (target tissues expect a certain concentration of a hormone)– normal tissue responses produced only when Hs present within their normal, or physiological

concentration range (what they are used to) • pharmacological levels – may cause a different effect than what you anticipate

– widespread & damaging side effects• THUS target tissue responsiveness is not only affected by varied numbers of Receptors on the target tissue but

also by Hormone concentration• Because cells are responsive to hormone concentration there are mechanisms that regulate how sensitive they

are to the hormone concentration by up or down regulation • H concentration variation can affect target cell responsiveness

– Upregulation (increase sensitivity)• a priming effect• prolonged low concentrations of H causes an increase in sensitivity

– An increase in receptor numbers– Downregulation (de-sensitivity)

• prolonged exposure to high concentrations of H can desensitize the target cell– A decrease in Receptor numbers

• pulsatile secretion rate (we want times of high without desensitizing and decrease in numbers)– May prevent desensitization or changing receptor numbers– Growth hormone– best time to grow is at night, more active at night and falls during the

day– Gonadotropins (FSH, LH) have hills and valleys over the length of the day

• Hs can up- or down-regulate their own receptors, as well as receptors for other Hormones– permissiveness is an important Hormone-Hormone interaction

• why? Thyroid hormone is notorious for this – Hormone that has an impact on a cell may induce an increase in receptor numbers for a

second hormone, thus increase effectiveness of the 2nd hormones • You don’t need as much, you can increase sensitivity before even seeing the

hormone – Take a cell and prep it for what is about to come

Hormone Delivery

• Endocrine– messenger is bloodborne (also in lymph) • Neuroendocrine- released by a neuron in a fluid-- bloodborne (neurosecretory cells) neurons that behave like an

endocrine cell• Paracrine- hormone released diffuses to adjacent target cells through extracellular space• Autocrine- hormone released and feedbacks on the cell of origin

– Are these truly hormones? They don’t travel any distance!

• Neurocrine– the neuron comes in contact with target cell and hormone is released in synaptic cleft denoting an endocrine influence on or by nerves

– Different than NT? There is a neuron that is releasing a chemical messenger that impacts another neuron but it’s not in the characteristics of NT but serves as a hormone– has an endocrine influence on the nerve

• longer lasting effect• Instead of causing a synaptic potential it has another effect – increase metabolism or change

protein it is making.

Mechanisms of Hormone Action • Although each Hormone exerts its own characteristic effects on target cells, Hormones that are in the same

chemical category have similar mechanisms of action• Secretory cell release regulatory molecule move into blood circulation and impact target cell that has a receptor

for that hormone• Similarities involve location of Receptors and the event that occur in the target cell after Hormone binding to

Receptor• H-R (hormone-receptor) interactions are highly specific with binding occurring with high affinity and low capacity

o You don’t need a lot for a strong effect because all you need is a hormone bound to a receptor. If nothing is there to take the hormone off it will continue to have its affect.

Hormones that Bind to Nuclear Receptors

Lipids bind to nuclear receptors Typically impact target cell by stimulating genetic transcriptiongenomic action

– Lipids derived hormones like steroids Lipophilic with carrier proteins and hydrophobic– released at target cell and bind to a receptor proteins

• Receptor protein domains Cytosolic it will translocate into cell itself Ligand Binding Domain: steroid binds to receptor protein serving as a transcription

factoro DNA binding domain- DNA in complex where it will bind to ( hormone response

element) o Two half sites (need the two to dimerize to cause target gene to be transcribed)o Activates a gene that is found downstream

Homodimer- if two hormone receptor complexes are the same Nongenomic action have affect really quickly; action caused by lipophilic hormone that cannot be explained.

Think that there is a plasma membrane binding receptor that causing cellular affect.

Hormones that use Second Messengers• Hormones that cannot pass through the plasma membrane utilize surface receptors on the plasma membrane

– Peptide hormone can’t get through plasma membrane so it binds to a receptor in plasma membrane• how does it stimulate effect? When first messenger binds to receptor it causes second messengers

– Exert effects via intracellular mediators, second messengers – First messenger (Hormone) binds to receptor and activates G protein, alpha subunit disassociates binds

to affecter enzyme adenylate cyclase making cAMP which influenced protein kinases– Activation of G protein – activates phospholipase C (effector enzyme in membrane that breaks down

phospholipid into DAG and IP3) IP3 – intracellular meditators and causes ER to release Ca for cellular effects.

– Some cells you both mediators others only use one- depends on which pathway is available…all depends on the cell

Insulin Receptor • Insulin (decreases blood glucose levels) promotes uptake of glucose and amino acid transport as well as

glycogen, fat and protein synthesis in target organs—liver, skeletal muscle and adipose tissue • Two half receptors – insulin molecule binds to cause an auto phosphorylation within receptor causing chemical

changes in receptor becoming an active tyrosine kinase – the insulin receptor become the effector enzyme• Tyrosine kinase receptor phosphorylates a signaling proteins which will become the intracellular mediator to

cause cascade effect within cell. • When insulin binds there is a cascade effect that generates signaling molecules that cause vesicles with glucose

transport to the plasma membrane– insert carrier proteins into plasma membrane and promote facilitated diffusion (passive- need a concentration gradient) for glucose- increase uptake by the cell and lowering blood

glucose levels

Example: Action via Two Second Messenger Systems • How a hepatocyte responds to epinephrine.• Presence of different second messenger

systems permit signaling molecules to have varying effects on the target cell

• Hepatocytes can display 2 receptors beta adrenergic and alpha adrenergic receptors

• Bind to beta adrenergic R it activates adenylate cyclase forming cAMP and active protein kinase thus activated glycogen break down into free glucose to be released by hepatoyte

• There are 2 second messenger systems• You can initiated 2 second messenger systems

to cause two different effects • Alpha adrenergic receptors when epinephrine binds it initiating influx of calcium and binds to calmodulin

(binding up to 4 Ca) and activates a protein kinase that initiates glycogen break down into free glucose.

Pituitary Gland • Aka Hypophysis hanging by a stalk like structure (infundibulum) found in the sella turcica of the sphenoid bone • Anterior and posterior lobe- two separate glandsArise from two different embryos– 2 organs structurally and

functionally different• Anterior pituitary (glandular) = adenohypophysis

– Prolactin target mammary glands stimulating milk production (guys make prolactin too), kick in during puberty

– PIH prolactin inhibitor in males to suppress prolactin (made more in male than females), keep in during puberty

• Gynecomastia– breast development in males – Growth hormone--- somatotropin; targets a variety of tissues but especially in adolescence and puberty

it targets bone, skeletal muscle and fat promoting amino acid uptake and then into proteins--- involved in overall tissue & organ growth; stimulates the metabolism of fat stores by pushing cells to utilize fat for fuel (encouraging using lipids for energy)

• Decrease in glucose uptake by cells – discourage taking up glucose for energy causing glucose to stay outside the cell known as the glucose sparing effect of GH

• Glucose is elevated in blood circulation in turn known as diabetogenic effect • Initiates Break down of glycogen in storage site like the liver into glucose

– TSH- thyroid stimulating hormone– ACTH- stimulates the adrenal cortex (outer layer of adrenal gland) – Gonadotropins- first found in females; together they regulate gamete formation and production of

steroids• LH– involved with sex steroid production

- Also called interstitial cell stimulating hormone in male• FSH- supports gamete formation

• Tropic hormone- hormone produced by anterior pituitary that then affects/influences another endocrine gland – ACTH, TSH, LH, FSH– GH maybe?

• Trophic hormone– any hormone that can cause an increase in gland or tissue growth, non-endocrine effect • POMC– proopiomelanocortin produced be cells of pars intermedia (only in humans during fetal development),

can be clipped to for ACTH• Posterior Pituitary (neural) = Neurohypophysis – hormones synthesized by neurosecretory cells of hypothalamic

nuclei – PVN & SON – Posterior pituitary stores and releases hormones but does not synthesize them aka pituicytes– Stores and Releases hormone but does NOT produce any

– Hormones are made by Neurosecretory cells from hypothalamus – neurons that act like endocrine cells and release their hormone in posterior pituitary

• Cell bodies in two nuclei and axons terminate in posterior pituitary – PVN (paraventricular nucleus)- produce oxytocin more noted in females because involved with initiation

of childbirth– positive feedback mechanism • In males: sexual arousal and behavior; cuddle hormone

– SON (supraoptic nucleus) – produced ADH (antidiuretic) which shuts down urine formation; holds water when dehydrated

– Pituicytes like glial cells/support cells that do not synthesize hormone; assist with the release of hormones and supporting neurosecretory cells

Hypothalamus-Pituitary Relationships• There is a very relationship between the pituitary gland and hypothalamus • Hypothalamo-hypophyseal tract

– Collection of axons in CNS– Neurosecretory cells in SON and PVN travel down through infundibulum and terminate in posterior

pituitary--- travel along this tract– DIRECT because hormones are released in hypothalamus and sent to posterior pituitary (not put out

into circulation)– Neuroendocrine reflex– sensory stimulus info observed by hypothalamus cause reflex secretion of

hormone from posterior pituitary • Ex. ADH-- Looks at blood osmolality when it increases(lose water) causes the neurosecretory

cells in SON to make and release ADH • Hypothalamo-hypophyseal portal system

– Deals with vascular network– Relationship between hypothalamus and anterior pituitary – Nuclei in hypothalamus that store releasing and inhibiting hormones released and picked up by Primary

capillary plexus (capillary bed) and shunt/portal venules– into secondary plexus into the anterior pituitary

– Protal venules- blood vessels that shunt hormones released by hypothalamus and bring them to anterior pituitary

– INDIRECT (put into circulation of blood- they don’t have to go to anterior pituitary can be picked up and put elsewhere)

Feedback Loops - Endocrine system regulated by feedback loops- Short loop (left diagram) vs long loop

- Hypothalamus initiated to released TRH (thryoidtropin releasing hormone) effect cells in anterior pituitary that affect TSH which feedback to hypothalamus and decreased in the released of TRH- short

- TSH can also go out in blood circulation can feedback on hypothalamus and influence thyroid gland and decreased in growth and make thyroxin– thyroxin levels can feedback and cause decreased in both TRH and TSH (LONG LOOP)

- (right diagram) Stimulus causes hypothalamus to release GnRH causing cells in Anterior Pituitary gonadotropins and influence gametogenesis and steroidogenesis in the gonads. How do we know which one to released gonadotropins? GnRH can signal BOTH to be released but we don’t want both at the same time. ACTION POTENTIALS

- The frequency of gnRH secretion causes the released either FSH or LH - What is an Axis relationship between endocrine organs and target organs; another name for feedback loops

Thyroid Gland• Thyroid Hormone Only hormone to be synthesized and stored extracellularly – actively transported in • Two lobes with Isthmus (small piece of tissue) connects the two • Highly vascularized • Made up of follicle- hollow sphere made of follicular/follicle cells (simple cuboidal epithelium)

– Within the follicle is protein rich material called colloid

• Thyroid follicle responds to TSH by increasing growth and support uptake of iodine from blood circulation – actively transport iodine to be pulled into thyroid

• Inner surface of follicle cells are enzyme that oxidize iodine and bring it to proteins thyroglobulin that hold iodine (one or two molecules can be attacked to tyrosin of thyroid globin) – make MIT or DIT (tyrosine and attach iodine)

• MIT (monoiodotyrosine) and DIT (diiodotyrosine)– Form T3—MIT + DIT– 2 DIT to form T4 (thyroxin)

• You will never make an MIT and MIT**• T3 and T4 bound to thryoglobin and follicle cell

endocytosize colloid stimulated by TSH and cleave off T3 and T4 released out to fluid to be picked up by blood

– T3 and T4 can be picked up by carrier protein in plasma • It is unique because the follicles do NOT make Thyroid hormone--- hormone is MADE EXTRACELLULARLY and

STORED EXTRCELLULARLY – only cleaved off from storage protein once its inside the follicle cells

• You make and store: 2-3 month supply of thyroid hormones– most hormones are not stored but made as needed

• Parafollicular cells – cells between the follicles (clear cells) that produce calcitonin- CT

Mechanism of Action for Thyroid Hormone• TH require a carrier protein – thyroxin binding globulin (AA derivative that act like a steriod) • Their receptor is found intracellularly (not on plasma membrane) • T4 is made A LOT but when taken up by cell but it is cleaved to form T3 because this is more biologically active • T4 also has cellular affects (made more) and many times is converted to T3 (we still make T3 just not as much)• T3 attached to binding protein to take to receptor which is found nuclearly already bound to its half site• The other half site is occupied by RXR receptor and does not bind T3 but binds a vitamin A derivative

o then they dimerize become one and functional– heterodimer- bc two sub parts are different and then initiate genetic transcription once dimerization occurs

• TH primarily function/ main effect is to influence cellular metabolism (make a change to metabolic process)• TH wears a cap to prepare cell for the next hormone (prepper)• When ligand is absent there are corepressor proteins that are bound to him to inhibit any gene transcription so

when T3 comes in it displaces the repressor protein to bind to in.

•

Thyroid Endocrinopathy• Endemic goiter—diet deficiency lack in iodine. You don’t have enough

thyroid hormones• Endocrinopathy – endocrine gland organ dysfunction • The feedback loop of thyroid gland– hypothalamus produced TRH causing

anterior pituitary to produce TSH--- thyroid can increase in size or produced thyroid hormones

• Inadequate iodine you cannot make T3 or T4 (even though you make normal levels of TRH and TSH) so they continue to make TRH an TSH because the cant see the T3 being made--- high levels causes hypertrophy of thyroid gland making a goiter

• Graves’ disease– leads to toxic goiter, thyrotoxicosis, makes antibodies that are just like TSH and bind to TSH receptors causing block feedback mechanism ending up with a goiter as well. The regulatory mechanism can work but u can’t regulate the antibodies that block feedback mechanisms

so you lose regulation – end up initiating thyroid gland to make more TH (hypersecretion and producing a goiter!)

o This system works fine but we make things that act like TH that really aren’t!

Parathyroid Gland• Primary regulator for blood calcium levels• CT, or calcitonin causes a decrease in blood calcium levels • Posterior lateral side of thyroid• Pairs of 2 to 4 • Produced PTH- to regulate blood calcium levels (usually

elevates calcium levels• Parathyroid glands serve as sensor• When it falls belong sufficient levels releases PTH

– Causes the breakdown of bone, dissolve it to take out calcium phosphates and put into blood circulations to increase blood calcium levels

– Kidneys- reabsorb calcium from urine to release into blood

• Primary regulators of blood calcium levels is PTH• Calcitonin decreases blood calcium levels released from the

thyroid (parafollicular cells)– If we have an elevation in blood ca level it

encourages Ca to be stored in bone – If we do not have enough calcium in diet it will pull

ca from the skeleton • PTH is more dominant than CT• Need vitamin D3 for the absorption of calcium from digestive system as we consume food

– Need vitamin D with calcium supplement or it won’t be absorbed– Also called calcitriol

Adrenal Glands• Sit on top of kidneys (triangle shaped) • Suprarenal gland (superior to kidney)• 2 layers: Outer cortex and inner medulla• Like pituitary gland! Cortex and medulla are like two separate organs like the anterior and posterior pituitary • Cortex is the outer layer that produce corticosteroids (glandular in appearance)

– Zona glomerulus (mineralocorticoids)• aldosterone that regulates sodium, potassium and water

– Middle layer Zona fasiculata (glucocorticoids- regulate glucose via cortisol and corticosterone) • Regulate protein breakdown and lipid mobilization• Gluconeogenesis– glucose made from a new source (non-carbohydrate sources)

– Zona reticularis (innermost) produce gonadocorticoids• Produce androgens and estrogens• During puberty hormones are thought to be involved initiating secondary sex characteristics • Gynocomastia: man boobs (more ductal breast tissue) – can be produced in males that smoke

weed on a regular basis • Medulla (innermost)– looks like nervous system

– Made of chromaffin cells – modified post ganglionic cells (very similar in sympathetic nervous system)– Produce catecholamine: effect similar to Sympathetic nervous system stimulation but longer effect

(epinephrine and norepinephrine) • Exogenous glucocorticoids used to reduce swelling but taking it regularly ***

– Corticol shoots reduce swelling, help immune system and decrease inflammation– Long term steroids can influence glucose regulatory pathways

– Given medically to suppress immune response/inflammation, because of metabolic actions- side effects include hyperglycemia and decrease glucose tolerance

Stress & the Adrenal Gland

• Stress can be thought of as a threat to homeostasis. Stress disrupts– Defined as the reaction of an organisms to stimuli called stressors, which may produce damaging effects

• Hypothalamus- the director of stress response• GAS—General Adaptation Syndrome – nonspecific response by body to readjust following demand, how you

respond to stress. (stress causing GAS, helps you deal with it) – Stage 1 – alarm reaction; adrenal gland is activated

• Initiate short term stress responses using the sympathoadrenal system • Sympathetic nervous system activates the adrenal medulla to release catecholamine which

causes a variety of effect- increase heart rate and blood pressure, dilation, metabolic rate – Stage 2 – stage of resistance

• Regulatory hormone released by hypothalamus called CRH which target cells via portal system in anterior pituitary that releases hormone ACTH to influence cortex

• Cortex releases mineralocorticoids and glucocorticoids—more long term response to stress – Stage 3- stage of exhaustion

• Individuals under stressed in long period of time (individualistic period of time)• Extended period of time• Losing their war with maintaining homeostasis and can lead to death***

Pancreas • Mixed gland—both endocrine and exocrine functions (heterocrine organ)• Insulin- enhances glucose absorption & utilization by body cells, to support growth and establish carbohydrate

and lipid reserves• pancreatic islets: mall pockets of endocrine cells where the hormones are produced • Two hormones that regulate blood glucose levels: insulin, glucagon • Alpha comes before beta, G comes before Insulin

• When our blood levels are above the range--Insulin targets every cells and initiates uptake and utilization of blood glucose

• Glucagon—promotes glucose synthesis & glycogen breakdown as well as mobilize lipid reserves – We get more energy from breaking down a fat than carb

• Decrease in blood glucose levels and glucagon is released to decrease the uptake and glycogenolysis to break down glycogen in liver stores to release glucose (Gluconeogenesis)

• Antagonist effects

Pineal Gland• Important role in humans- diencephalon • SAD—seasonal affective disorder: type of depression, “winter blues”

– Fewer hours of daylight we get sad• Melatonin (MT) produced by pineal gland: Signals NIGHT• Classified as a neuro hormone– comes from the CNS and endocrine hormone • involves vision to help register light• Light stimulation flows through a pathway known as retinohypothalamic tract• Suprachiasmatic nucleus is the biological clock and in charge of circadian rhythm– the rhythms of physiological

activity that follow a 24 hour pattern• Activates the sympathetic nervous system that the pineal gland releases melatonin• Not a direct effect – flows through different areas first• Biological “alarm clock”

– Period proteins, under control of genes (clock and BMAL 1) use SCN as timing center with GABA and VIP as important neurotransmitters for signaling systems

• Depends on how many period proteins that are there to tell if its day or night how does it circadian rhythms

• GABA is inhibitory and VIP are import NT in signaling system in this nucleus that send out signals to activate genes and period proteins

Other Hormone-Producing Structures• heart

– atrial natriuretic factor/peptide (ANF/ANP) - produced by atrial muscle cells & released in response to elevation in blood pressure

• decreases blood volume, Blood pressure and blood Na levels• counterbalances aldosterone

• gastrointestinal tract– variety of hormones released from individual enteroendocrine cells, which are found throughout GI tract– function to regulate digestive processes

• kidney– erythropoietin (EPO) signals bone marrow to increase RBC production

• skin– produces cholecalciferol when UV light strikes modified Cholesterol molecules (isomerized through UV

light and released into circulation liver kidneys formed into calcitriol– released into circulation and activated in kidney

• calcitriol (Vitamin D3)– important in Ca absorption in GI tract

• adipose tissue– leptin & resistin, peptide hormones

• leptin secreted by adipocytes throughout body following glucose & lipid uptake; has several functions but known for feedback control of appetite

– thought obesity could be regulated with leptin • resistin reduces insulin sensitivity throughout body-an insulin antagonist

Autocrine & Paracrine Regulation • observe other “classes” of regulatory molecules besides Neurotransmitters & Hormones

– produced & regulate within organ produced (very localized!)• paracrine regulators

– cytokines, Growth Factors s, Nitric Oxide, endothelins, bradykinins• autocrine regulators

– neurotrophins – eicosanoids, most diverse group of Autocrine and Paracrine regulators

• produced in almost every organ & implicated in a wide variety of regulatory functions – inflammation, capillary permeability

– thromboxane- platelet aggregation– prostaglandins- vasodilators or vasodilators

• starts with aracodinic acid

Endocrinopathies• result of hypersecretion, hyposecretion or receptor dysfunction • Dwarfism– example of hyposecretion of growth hormone• Acromegaly- hypersecretion of growth hormone in adulthood

o Would be called gigantism if occurs and diagnosed in youth.