LECTURE 16: AUTONOMIC AND NEUROENDOCRINE SYSTEMSREQUIRED READING: Kandel text, Chapter 49

Autonomic nervous system mediates visceral reflex responses that are involuntary and largely unconscious

Autonomic nervous system consists of:

1) Motor neurons which act on smooth muscle, cardiac muscle, and exocrine glands

2) “Preganglionic” CNS neurons whose axons synapse on these motor neurons

3) Visceral sensory neurons

4) Branches and subsets of external-sensing neurons (including somatosensory , olfactory, and retinal)

Autonomic postganglionic neurons release neurotransmitters which act through metabotropic receptors on target cells

Autonomic responses are coordinated with one another and with behavioral responses and emotions through the hypothalamus in the CNS

alwayscholinergic

cholinergic or

adrenergic

nicotinicreceptors

muscarinicor

adrenergicreceptors

EXAMPLES OF AUTONOMIC FUNCTION

Regulation of heartbeat rate

Regulation of vascular constriction/dilation

Pupil and lens ocular reflexes

Exocrine gland secretion

Glucose mobilization

Sweating and hair follicle erection

Bladder filling and emptying

Sexual responses

Alimentary and bronchial reflexes

Gut peristalsis

THREE DIVISIONS OF THE AUTONOMIC NERVOUS SYSTEM

Sympathetic nervous system

Parasympathetic nervous system

Enteric nervous system

Sympathetic system controls visceral responses that prepare the body for rapid, intense activity, often refered to as FIGHT-OR-FLIGHT REACTION.

Responses include accelerated heartbeat, central artery constriction, peripheral vascular dilation, liver glycogen metabolism, & rapid breathing.

Other sympathetic responses also work in balance with countering parasympathetic responses to maintain body homeostasis (counteraction to body stress).

Parasympathetic responses sometimes refered to as the REST-AND-DIGEST STATE.

Almost all visceral targets receive both sympathetic & parasympathetic neuronal inputs.

Enteric neurons form plexuses that surround and extend along the length of the gut, including stomach, small and large intestines.

Enteric system activate coordinated contraction of smooth muscles to cause peristaltic constriction of the gut.

Most of enteric nervous system functions independently of higher CNS control.

ANATOMY OF SYMPATHETIC & PARASYMPATHETIC NERVOUS SYSTEM

Most SYMPATHETICpostganglionic neurons are

adrenergic(release E or NE)

Most PARASYMPATHETICpostganglionic neurons are

cholingeric

Site of spinal cord lesion injury can be rapidly assessed by surveying damaged and surviving autonomic reflex responses

ANATOMY OF SYMPATHETIC & PARASYMPATHETIC NERVOUS SYSTEM

Generalized “FIGHT” responsemediated by sympathetic

activation of the adrenal gland,triggering epinephrine

secretion into circulation

ANATOMY OF ENTERIC NERVOUS SYSTEM

SENSORIMOTOR CONNECTIONS IN ENTERIC NERVOUS SYSTEMARE PREDOMINANTLY LOCAL

A local circuitry drives peristalsis in the intestines

FOODDISTENSIONP

ER

IST

AL

SIS

PRESSURE SENSING NEURON

CIRCULAR MUSCLEMOTOR NEURONS

Pressure-sensing neuron senses gut distension

Acts through interneurons to activate entericmotor neurons with axons projecting rostrally

causing squeezing of circular muscle behind the distension

Simultaneous inhibition of other motor neuronswith axons projecting caudally relaxes downstream

circular muscle

POST-GANGLIONIC NEUROTRANSMISSION LACKS TYPICALPRE- AND POST-SYNAPTIC SPECIALIZATIONS

Post-ganglionic neuron’s axon terminal lacks clear-vesicle docking machinery.

Multiple axonal swellings (varicosities) are sites of neurotransmitter vesicle accumulation.

Post-synaptic target (smooth muscle, gland, etc.) lacks post-synaptic density.

Target cell neurotransmitter receptors are broadly distributed on surface.

Released neurotransmitter acts diffusely over distances up to 1 mm.

Highly branched axons with multiple varicosities enable post-ganglionic neuronto act upon many cells in the target structure.

DIFFUSE TRANSMISSION FROM GANGLIONIC AXONS FACILITATEDDISCOVERY OF THE FIRST CHEMICAL NEUROTRANSMITTER

Parasympathetic vagus nerve activity slows heartbeat rate,while sympathetic accelerator nerve activity speeds heartbeat rate

TWO BEATING FROG HEARTS DISSECTED AND MAINTAINED IN SMALL VOLUME SOLUTION;HEART #1 DISSECTED WITH INNERVATING NERVES ATTACHED

HEART #2 DISSECTED WITHOUT NERVES

Stimulation of vagal nerve slowed beating of heart #1After stimulation, transfer of heart #1’s bathing solution to heart #2 slowed its beating

Stimulation of accelerator nerve speeds beating of heart #1After stimulation, transfer of heart #1’s solution to heart #2 sped its beating

THEREFORE, NERVE-INDUCED CARDIAC RESPONSES ARE THROUGHSECRETED CHEMICAL NEUROTRANSMITTERS

(Vagal transmitter later shown to be ACh, accelerator transmitter is NE)

MECHANISMS OF AUTONOMIC MODULATION OF CARDIAC FUNCTION

Parasympathetic release of acetylcholine reduces cardiac output in two ways

Sympathetic release of norepinephrine increases cardiac output in two ways

1) Muscarinic generation of G directly activates a potassium channel (GIRK) in pacemaker cardiocytes, which slows their depolarization and rate of heartbeat.

2) Muscarinic generation of Gi in heart muscle lowers cAMP and PKA levels, causing reduced opening of L-type calcium channels, thereby reducing force of heart contraction.

1) 1-adrenergic generation of Gs in pacemaker cardiocytes elevates cAMP and PKA levels, which reduces the threshold voltage for action potential initiation, thereby increasing rate of heartbeat.

2) 1-adrenergic elevation of cAMP and PKA in heart muscle increases opening of L-type calcium channels, thereby increasing force of heart contraction.

SENSORY INPUTS TO AUTONOMIC FUNCTION

Our bodies sense deleterious changes and undertake automatic responsesto maintain homeostasis.

Sensory inputs eliciting autonomic responses include:

1) External sensations which trigger corrective reflexes

Examples: a) Ocular reflexes -- pupil dilation or constriction in response to light,lens stretching to adjust focus

http://library.med.utah.edu/kw/hyperbrain/anim/reflex.html

b) Painful laceration -- vasoconstriction to limit blood losssympathetic activation of coordinated fight/flight responses

2) Visceral sensations induce homeostatic responses

Examples: a) Opposing sympathetic/parasympathetic control of heartbeat and blood pressure --

If sympathetic activity drives heartbeat and artery constriction too much,pressure-sensitive sensory afferents in the aorta trigger the baroreceptor reflex,

which includes parasympathetic vagal input to heart and induction ofarterial dilation

http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter21/animation__baroreceptor_reflex_control_of_blood_pressure.html

Reciprocally, pressure-sensitive sensory afferents in the cardiac right atriam sense distentiontriggering the right atrial reflex, by which sympathetic accerelerator nerve firing speeds rate

b) Irritants to oronasal cavities act through parasympathetic gangliato trigger nasal and lacrimal glandular secretions

PREGANGLIONIC FIBERS RELEASE SMALL MOLECULE AND PEPTIDENEUROTRANSMITTERS TO ELICIT COMPLEX GANGLIONIC NEURON RESPONSES

Single or low-frequency preganglionic firing releases Ach which activates nicotinicreceptors triggering fast EPSP in postganglionic neuron.

High-frequency stimulation releases more Ach and LHRH peptide. The complexpostganglionic response consists of fast EPSP, slow IPSP mediated bymuscarinic receptor activation of GIRKs, and delayed EPSP resulting

from LHRH binding to peptidergic receptors.

SENSORY PATHWAYS OF SYMPATHETIC AND PARASYMPATHETIC SYSTEMSPASS LOOP THROUGH BRAIN STEM, BUT ALSO PROJECT TO CONSCIOUS CORTICAL AREAS

ASCENDING VISCERALSENSORY PATHWAYS

DESCENDING AUTONOMICRESPONSE PATHWAYS

HYPOTHALAMUS COORDINATES PHYSIOLOGY AND BEHAVIORIN RESPONSE TO VISCERAL SENSORY INPUTS

EXAMPLE: BLOOD OSMOLARITY HOMEOSTASIS

VISCERAL SENSORY INPUTS

Blood pressureBlood osmolarity

HYPOTHALAMUS COORDINATED OUTPUTS

Autonomic -- action on smooth muscles in central and peripheral vasculature

Behavioral -- conscious thirst which drives search for fluid intake

Endocrine -- secretion of vasopressin into blood, which promotes water resorption by kidneys

HYPOTHALAMUS CONTROLS HORMONE RELEASE FROM PITUITARY GLANDBOTH DIRECTLY AND INDIRECTLY