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The Nervous Impulse

• Dependent upon a across the cell membrane The Nervous System – Magnitude of potential is determined by • Leakage channels for sodium and potassium • Active transport carriers (Sodium/Potassium pump) Neural Signaling – The is polarized Chapter 11 • Impulse results from

The concentrations of Na + and K + on each side of the membrane are different. Factors that contribute to resting Outside cell + The Na concentration Na + is higher outside the K+ (5 m M ) (140 m M ) cell.

The K + concentration + K Na + is higher inside the (140 m M ) (15 m M ) + + cell. Inside cell Na -K ATPases (pumps) maintain the concentration gradients of Na + and K + across the membrane. The permeabilities of Na + and K + across the membrane are different. + + Suppose a cell has only K channels... K leakage channels + K+ K+ K loss through abundant leakage channels establishes a negative membrane potential.

+ + Cell interior K K –90 mV Now, let’s add some Na + channels to our cell... K+ K+ Na + Na + entry through leakage channels reduces the negative membrane potential slightly.

K K+ Na + Cell interior –70 mV

Na+-K+ pump Finally, let’s add a pump to compensate K+ K+ Na + for leaking ions. Na +-K+ ATPases (pumps) maintain the concentration gradients, resulting in the resting membrane potential.

Check out the A&P Flix on Mastering “Resting Membrane Potential” K+ K+ Na + Cell interior –70 mV

Figure 11.8

Voltmeter The Nervous Impulse

• Polarization Plasma Ground electrode – membrane outside cell Voltage across the plasma membrane – Inside of the cell is more negative than the outside Microelectrode inside cell • Resting potential – Axon Polarization leads to attraction between opposite charges across the membrane – When a neuron is at rest, average potential is -70mV • use changes in membrane potential as Neuron signals to receive, integrate, and send information

Figure 11.7

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The Nervous Impulse Depolarizing stimulus

• Types of changes Inside – Depolarization positive • Decrease in membrane potential (interior becomes less Inside negative) negative Depolarization – Hyperpolarization • Increase in membrane potential (inside becomes more Resting negative) potential

Time (ms) (a) Depolarization: The membrane potential moves toward 0 mV, the inside becoming less negative (more positive). This increases the probability of nerve impulse production. Figure 11.9a

Hyperpolarizing stimulus The Nervous Impulse

• Changes in polarization are produced by… – Anything that changes ion concentration across the membrane – Anything that changes membrane permeability to

Resting an ion (most important) potential • Largely due to changes in the number of open ion channels Hyper- polarization • Membrane channels – Chemically gated (ligand gated) Time (ms) (b) Hyperpolarization: The membrane – potential increases, the inside becoming Voltage gated more negative. This decreases the probability of nerve impulse production.

Figure 11.9b

The Nervous Impulse

• There also are mechanically gated membrane Receptor chemical attached to receptor Na + + channels Na Na + Na + – Open in response to physical deformation (touch, Chemical Membrane binds voltage pressure, sound waves) changes – K+ Found in sensory receptors K+

Closed Open Closed Open (a) Chemically (ligand) gated ion channels open when the (b) Voltage-gated ion channels open and close in response appropriate neurotransmitter binds to the receptor, to changes in membrane voltage. allowing (in this case) simultaneous movement of Na + and K +.

Figure 11.6

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The Graded Potential

• Short lived, localized changes in membrane potential Stimulus Depolarized region – Due to incoming signals, usually energy or • Channels open → ions flow • Short distance signals Plasma membrane • May be depolarization or hyperpolarization events

(a) Depolarization: A small patch of the membrane (red area) has become depolarized.

Figure 11.10a

Active area (site of initial depolarization)

–70

Membranepotential (mV) Resting potential (b) Spread of depolarization: The local currents (black arrows) that are created depolarize Distance (a few mm) (c) Decay of membrane potential with distance: Because current adjacent membrane areas and allow the wave of is lost through the “leaky” plasma membrane, the voltage declines depolarization to spread. with distance from the stimulus (the voltage is decremental ). Consequently, graded potentials are short-distance signals.

Figure 11.10b Figure 11.10c

The Stimuli that Initiate Action Potentials óLong distance signal óInitiated by sufficient depolarization at site of Sensory Neurons Motor & Association Neurons • graded potential Light • Chemical stimuli • ó Must reach threshold – usually a change of ~100mV Heat from other óOpening of specific voltage gated channels • Chemicals neurons óDoes not decrease in strength with distance • Mechanical energy ó“All or none” óA.K.A. nerve impulse Threshold stimulus always required

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Dendrites Cell body Neuron cell body The Action Potential (receptive (biosynthetic center regions) and receptive region) óThe players:

Sodium Na + channel Potassium channel

Nucleolus

Activation gates K+ Inactivation gate

Axon (a) (impulse Dendritic Potassium Channel spine Nucleus conducting Impulse region) direction ó Slow to open Nissl bodies Node of Ranvier • Opens instantly Axon terminals • Can’t sustain (self-inhibits) ó Slow to close Axon hillock Schwann cell (secretory (impulse Neurilemma (one inter- region) (b) generating node) Terminal region) branches

The events Sodium Na + The big picture channel Potassium channel 1 Resting state2 Depolarization 3 Repolarization

Activation gates K+ Inactivation gate Na + Na + 1 Resting state 3 4 Hyperpolarization

2 Action K+ potential K+

4 Hyperpolarization Na + 2 Depolarization

Membrane potential (mV) potential Membrane Threshold

1 1 4

K+ Time (ms)

3 Repolarization

Figure 11.11 (1 of 5)

The Action Potential The Action Potential

• Resting potential is quickly restored • Once initiated, AP is self-propagating – Thousands of Na +/K + pumps redistribute ions – Once Na + channels in one region are inactivated, no – May seem like a huge task new AP is generated there – Only a small number of ions actually cross the • Continues along axon in one direction at membrane constant velocity • Change in 0.012% of intracellular Na + concentration • Factors affecting conduction velocity: – Axon diameter – larger diameter = faster conduction – Degree of myelination

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The Action Potential The Action Potential • Myelinated Neurons • Refractory period – Nodes of Ranvier – only place where current can – Neuron cannot respond to a second stimulus pass through the membrane • During repolarization – Saltatory conduction – 30X faster than continuous – Limits number of impulses per second conduction

Absolute refractory Relative refractory period period The Action Potential

Depolarization (Na + enters) • Coding for stimulus intensity – All APs are independent of stimulus strength – CNS must discern strong from weak signals to initiate appropriate response Repolarization – (K + leaves) Stimulus intensity is coded for by frequency of action potentials

After-hyperpolarization

Stimulus

Time (ms)

Figure 11.14

Dendrites Cell body Neuron cell body The Synapse (receptive (biosynthetic center regions) and receptive region) • Nervous system operates through chains of neurons connected by synapses • Syn = “to clasp or join” Nucleolus • Junction between… – Adjacent neurons

Axon – Neuron and an effector cell (a) (impulse Dendritic spine Nucleus conducting Impulse • region) direction Mediates information transfer Nissl bodies Node of Ranvier – Electrical Axon terminals ? Axon hillock Schwann cell (secretory (impulse – Neurilemma (one inter- region) Chemical (b) generating node) Terminal region) branches

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The Synapse

• Presynaptic neuron – Axodendritic Conducts impulses toward the synapse synapses • Postsynaptic neuron Dendrites – Axosomatic Transmits impulses away from the synapse synapses • Most neurons are both Cell body Axoaxonic synapses

(a) Axon

Axon of presynaptic The Synapse neuron • Electrical Synapses – Direct transmission of electrical signals from one cell to another Axosomatic – Less common than chemical synapses synapses • Neurons are electrically coupled (joined by gap junctions) • Communication is very rapid – May be unidirectional or bidirectional • Important in – Embryonic tissue Cell body (soma) – Some brain regions of postsynaptic – Synchronizing groups of neurons (example: jerky eye movements) (b) neuron

Electrical Synapses The Synapse

• Chemical Synapses – Indirect communication between cells – Electrical signal of AP is changed to a chemical signal (neurotransmitter) in the presynaptic neuron – Neurotransmitter is released into the synaptic space and diffuses toward the postsynaptic neuron – Postsynaptic neuron changes chemical signal back to electrical signal for conduction along its own axon – Unidirectional – Here’s how it works…

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Chemical Synapses Chemical Synapses

1. Action potential 2. Voltage-gated arrives at the Ca 2+ channels in open, and Ca 2+ the presynaptic enters the axon neuron terminal

Chemical Synapses Chemical Synapses

3. Ca 2+ entry causes 4. Neurotransmitter synaptic vesicles diffuses across the to release synaptic cleft and neurotransmitter binds to specific by exocytosis receptors on the postsynaptic neuron’s membrane

Chemical Synapses Chemical Synapses

5-6. Binding of the 7. Graded neurotransmitter potentials opens ion become nerve channels and impulses and are creates graded conducted to the potentials in the next cell in the postsynaptic chain neuron

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The Synapse EPSPs

• Postsynaptic membranes generally do not • Excitatory Postsynaptic Potentials (EPSP) generate action potentials – Depolarizes postsynaptic cell membrane • When the neurotransmitter binds, one of two – Excitatory neurotransmitters types of graded potential occur – Helps trigger AP at the axon hillock – Excitatory Postsynaptic Potentials (EPSP) – Inhibitory Postsynaptic Potentials (IPSP)

Dendrites Cell body Neuron cell body (receptive (biosynthetic center regions) and receptive region) An EPSP is a local depolarization of the postsynaptic membrane that brings the neuron closer to AP threshold. Neurotransmitter binding Nucleolus opens chemically gated Threshold ion channels, allowing the simultaneous pas- sage of Na + and K +.

Axon

(a) potential(mV) Membrane (impulse Dendritic spine Stimulus Nucleus conducting Impulse region) direction Nissl bodies Node of Ranvier Axon terminals Time (ms) Axon hillock Schwann cell (secretory (impulse Neurilemma (one inter- region) (a) Excitatory (EPSP) (b) generating node) Terminal region) branches

Figure 11.18a

IPSPs An IPSP is a local hyperpolarization of the • Inhibitory Postsynaptic Potentials (IPSP) postsynaptic membrane – and drives the neuron Hyperpolarizes postsynaptic cell membrane away from AP threshold. – Increases membrane permeability to K + or Cl - Neurotransmitter binding opens K + or Cl – channels. – Inhibitory neurotransmitters Threshold – Decreases chance of AP

Membrane potential(mV) Membrane Stimulus

Time (ms) (b) Inhibitory postsynaptic potential (IPSP)

Figure 11.18b

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Neurotransmitters Neurotransmitters

• Excitatory • Inhibitory – Acetylcholine – • Receptors also activated by Serotonin (brain, GI tract) nicotine, muscarine – GABA (brain and retina) – Norepinephrine – Glycine (spinal cord, brain, • Most common NT used by the sympathetic nervous and retina) system – Glutamate • Most abundant NT in vertebrates • Component of concern in MSG

Thought Question The Synapse

Strychnine is a pesticide that is used against small • Inactivation of NT’s vertebrates (birds, rodents). This chemical is an 1. Diffusion antagonist to glycine. What symptoms might an 2. Reuptake animal or human experience if they ingest this 3. Degradation (enzymatic inactivation) substance? • Examples – Cholinesterase & Ach • Found in synapses – Monoamine Oxidase & Norepinephrine (many others) • Bound to mitochondrial membrane in most cells

Chemical synapses transmit signals from one neuron to another using neurotransmitters. The Synapse Presynaptic neuron

Presynaptic Postsynaptic neuron neuron • Pharmacology

1 Action potential arrives at axon terminal. – 2+ Anticholinesterase neurotoxins 2 Voltage-gated Ca 2+ channels open and Ca Mitochondrion enters the axon terminal. Ca 2+ Ca 2+ • Ca 2+ Causes excitotoxicity (overstimulation) Ca 2+ 3 Ca 2+ entry causes Synaptic • neurotransmitter- cleft Example: Organophosphates, Nerve Gas containing synaptic Axon terminal Synaptic vesicles to release their vesicles contents by exocytosis. – 4 Neurotransmitter Local Anesthetics diffuses across the synaptic cleft and binds to specific Postsynaptic receptors on the neuron + postsynaptic membrane. • Block Na channels

Ion movement Enzymatic • Graded potential degradation Inhibitory Reuptake

Diffusion away • from synapse Example: Lidocaine

5 Binding of neurotransmitter opens ion channels, resulting in graded potentials. 6 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse.

Figure 11.17

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The Synapse Neural Integration

• Cocaine • Summation – Prevents dopamine reuptake – A single EPSP cannot induce an action potential – In response, the brain stops making dopamine • EPSP’s can summate to reach threshold – User unable to experience pleasure without the – IPSP’s can also summate with EPSP’s drug • Cancel each other out

Summation

E1 E1 • Types – Temporal summation • One or more presynaptic neurons transmit impulses in Threshold of axon of rapid-fire order postsynaptic neuron Resting potential – Spatial summation • Postsynaptic neuron is stimulated by more than one E1 E1 E1 E1 Time Time terminal at the same time (a) No summation: (b) Temporal summation: 2 stimuli separated in time 2 excitatory stimuli close cause EPSPs that do not in time cause EPSPs add together. that add together.

Excitatory synapse 1 (E 1)

Excitatory synapse 2 (E 2)

Inhibitory synapse (I 1)

Figure 11.19a, b

Neuronal Integration

E1 E1 • Neurons function in groups, and each group

E2 I1 contributes to wider neuronal function • There must be integration – the parts must work together to form a more complex whole

E1 + E 2 I1 E1 + I 1 Time Time (c) Spatial summation: (d) Spatial summation of 2 simultaneous stimuli at EPSPs and IPSPs: different locations cause Changes in membane EPSPs that add together. potential can cancel each other out.

Figure 11.19c, d

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Simple Neuronal Pool Neuronal Integration

• First level of neuronal integration: neuronal Presynaptic pools (input) fiber • Patterns of connections within a neuronal pool: neuronal circuits • Features – Allow for a wide variety of neuronal interaction – May consist of thousands of neurons – Often include excitatory and inhibitory neurons

Facilitated zone Discharge zone Facilitated zone Figure 11.21

Neuronal Circuits

• Diverging circuit – One incoming fiber stimulates an ever-increasing number of fibers – May affect a single pathway or several – Common in both sensory and motor systems – Example: A single neuron in the brain can activate 100 or more motor neurons in the spinal cord and thousands of fibers

Figure 11.22a

Neuronal Circuits

• Converging circuit – Opposite of diverging circuits – Results in either strong stimulation or inhibition – Also common in sensory and motor systems – Example: Different sensory stimuli can elicit the same memory

Figure 11.22c, d

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