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CHAPTER 43

NEUROSCIENCE I: CELLS OF THE

NERVOUS SYSTEM

Prepared by

Brenda Leady, University of Toledo

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Nervous system

Central nervous system (CNS) – brain and spinal cord

Peripheral nervous system (PNS) – all neurons and projections of their plasma membranes that are outside of the CNS

In certain invertebrates with a simple nervous system, the distinction is not clear or not present

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Neurons

Cells in the nervous system that send and receive electrical and chemical signals to and from other neurons throughout the body

All animals except sponges have neurons Number varies widely as a function of size

and behavioral complexity

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Neuron structure Cell body or soma – contains nucleus and organelles Dendrites

Extensions of plasma membrane May be single or branching Incoming signals

Axons Extension of plasma membrane Typically single Sending signals Axon hillock near cell body Terminal branches or nerve terminal at far end

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Glia

Perform various support functions 10 to 1,000 times more numerous than neurons Oligodendrocytes (CNS) and Schwann cells (PNS)

make myelin sheath Astrocytes – metabolic support Microglia – remove cellular debris Radial glia – form tracks for neuronal migration in

embryos Radial glia and astrocytes function as stem cells to

produce more glial cells and neurons

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3 types of neurons

Sensory neuronsDetect information from the outside world or

internal body conditionsAfferent neurons – transmit to CNS

Motor neuronsSend signals away from CNS (efferent neurons)

to elicit response Interneurons

Form complex interconnections between other neurons

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Reflex arc Stimulus from sensory neurons sent to CNS,

little or no interpretation, signal transmitted to motor neurons to elicit response

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Electrical properties

Membrane potentialDifference in charge inside and outside the cellPlasma membrane barrier separating charges Ion concentrations differ between the inside and

outside of the cellPolarized

Resting membrane potential When neurons not sending signals

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Squid giant axons used extensively

Voltmeter records the voltage difference between the microelectrodes inside and outside the neuron

Measure of membrane potential

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Plasma membrane selectively permeable to cations and anions

-70mv resting potential inside cell Interior more negative than exterior

Negative ions within the cell are drawn to the positive ions arrayed on the outer surface

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3 factors contributing to resting potential

1. Na+/K+ -ATPase (sodium-potassium pump Transports 3 Na+ out for every 2 K+ moved in

2. Ion specific channels allow passive movement of ions K+ channels open more frequently at resting

potential Membrane more permeable to K+

3. Negatively charged molecules such as proteins more abundant inside cell

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Electrochemical gradient

Combined effect of electrical and chemical gradient

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Opposing forces of chemical and electrical gradients can create an equilibrium where there is no net movement

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Signaling by neurons

Changes in membrane potential are changes in the degree of polarization

Depolarization – cell membrane less polarized, less negative relative to surrounding solution Gated channels open allowing Na+ to flow in and

membrane potential becomes more positive Hyperpolarization – cell membrane more

polarized, more negative K+ moves out of the cell making the cell membrane

less positive

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All cells have a membrane potential Only neurons and muscle cells are excitable

– capacity to generate electrical signals Use gated ion channels

Voltage-gated – open and close in response to voltage changes

Ligand-gated – open and close in response to ligands or chemicals

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2 types of changes

1. Graded potentials Depolarization or hyperpolarization Varies depending on strength of stimulus Occur locally, spreads a short distance, and

dies out

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2. Action potentials Always the large same amplitude

depolarization All-or-none Actively propagated or regenerative

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Begins when graded potential depolarizes to threshold potential (-50mV)

Voltage-gated Na+ channels open triggering action potential

Na+ rapidly diffuses into cell causing characteristic spike

Inactivation gate in Na+ channel swings shut after 1 msec (will not reopen until resting potential restored)

Action potential sequence

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Voltage-gated K+ channels also opened by threshold potential but 1 msec later than Na+ channels

K+ leave cell and membrane becomes negative again

So many K+ leave that membrane hyperpolarizes

Voltage-gated K+ channels close and resting membrane potential restored

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Evolution of K+ channels with a slightly slower opening time than Na+ channels was a key event that led to the formation of nervous systems

If both opened at the same time, they would negate each other’s effects

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Refractory periodWhile inactivation gate of Na+ closed, cell is

unresponsive to another stimulusPlaces limits on the frequency of action

potentialsAlso ensures action potential does not move

backward toward cell body

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Conduction

Na+ enters and threshold potential reached at axon hillock

Triggers opening of voltage-gated Na+ channels in hillock region

Depolarizes area nearer axon terminus Sequential opening of Na+ channels conducts

a wave of depolarization from axon hillock to axon terminus

Inactivation gate of Na+ channels prevents backward movement toward cell body

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Speed varies based on

Axon diameterBroad axons provide less resistance and action

potential moves faster Myelination

Myelinated faster then unmyelinatedOligodendrocytes and Schwann cells make

myelin sheathNot continuous – gaps at nodes of RanvierSaltatory conduction – action potential “jumps”

or flows through cytosol to next node

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Synapses

Junction where nerve terminal meets a neuron, muscle cell, or gland

Presynaptic cell (sends signal), synaptic cleft and postsynaptic cell (receives signal)

2 typesElectrical – electric charge freely flows through

gap junctions from cell to cellChemical – neurotransmitter acts as signal from

presynaptic to postsynaptic cell

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Presynaptic nerve cell contains vesicles of neurotransmitter

Exocytosis releases neurotransmitter into synaptic cleft

Diffuses across cleft Binds to channels or receptors in

postsynaptic cell membrane

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Binding of neurotransmitter changes membrane potential of postsynaptic cell

Excitatory postsynaptic potential (EPSP)Brings membrane closer to threshold potential

Inhibitory postsynaptic potential (IPSP)Takes membrane farther from threshold potential

(hyperpolarization) Synaptic signal ends when neurotransmitter

broken down by enzymes or taken back into presynaptic cell for reuse

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Neuron response

A neuron may receive multiple inputs from many synapses

Synaptic integration or summationMany EPSPs generated at one time sum

together to go to threshold potential Location also important

Synapses close together or close to axon hillock activated at the same time can work together to reach threshold potential

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Neurotransmitters

More than 100 in animals Categorized by size or molecular structure Excitatory and inhibitory neurotransmitters

Like brake and accelerator on a car

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5 classes of neurotransmitters

1. Acetylcholine One of most widespread neurotransmitters Released at neuromuscular junctions Excitatory in brain and skeletal muscles but

inhibitory in cardiac muscles

2. Biogenic amines Abnormally high or low levels associated with a

variety of disorders (schizophrenia, Parkinson disease, and depression)

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3. Amino acids Glutamate most widespread excitatory

neurotransmitter GABA (gamma aminobutyric acid) most common

inhibitory neurotransmitter

4. Neuropeptides Often called neuromodulators – can alter response

of postsynaptic neuron to other neurotransmitters Opiate peptides, enkaphalin, oxytocin

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5. Gaseous neurotransmitters Not sequestered into vesicles Produced locally as needed Short-acting to influence other cells by diffusion Several drugs for male sexual dysfunction

enhance erections by increasing or mimicking action of NO on smooth muscle

Function of CO uncertain

Loewi Discovered Acetylcholine

Interested in how nerves communicate with muscles A certain nerve attached to heart increased

contraction rate while another nerve decreased it Placed 2 frog hearts in separate but connected

chambers Stimulated on heart to slow rate Within a few minutes the other heart that had not

been stimulated also slowed Acetylcholine first neurotransmitter discovered

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Postsynaptic receptors

Same neurotransmitter can have excitatory or inhibitory effects

Response of postsynaptic cell depends on receptor type

Ionotropic receptors – ligand-gated ion channels open in response to neurotransmitter

Metabotropic receptors – G-protein coupled receptors initiate changes in postsynaptic cell

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Neurotransmitter Receptors Have Varied Subunit Compositions

GABA is an inhibitory neurotransmitter that opens Cl- channels Ionotropic receptor allows Cl- to flow in causing hyperpolarization

of plasma membrane One GABA receptor composed of 5 subunits Group of homologous genes encodes at least 16 different

subunits (plus alternative splicing) Each type of subunit has unique properties to fine-tune function

of GABA receptor Differ in effects of GABA binding and rate of Cl- movement May also differ in ability to recognize molecules other than GABA Ethanol depresses brain and muscle activity by binding to GABA

receptors

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Impact on public health

Neurotransmission disorders Genetic processes can increase or decrease synaptic

activity affecting emotions and behavior Major depression thought to result from decreased

activity of synapses releasing biogenic amines

Recreational drugs Enhance or interfere with neurotransmission Drugs produce changes or imbalances in

neurotransmission

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Conduction disordersCretinism – axons fail to become myelinated

during fetal life due to insufficient thyroid hormone in fetus

Multiple sclerosis (MS) – patient’s own body destroys myelin as if it were a foreign substance impairing function of myelinated neurons controlling movement, speech, memory, and emotion