Physiological PsychologyPhysiological Psychology

PSYC-465PSYC-465

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NeurophysiologyNeurophysiology

Systems and Circuits

What level(s) of analysis?What level(s) of analysis?

Synapses and Neurons

Genes and Molecules

Behavior and Cognition

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Recording the Membrane Recording the Membrane PotentialPotential

Experimental setup to record a neuron’s membrane Experimental setup to record a neuron’s membrane potentialpotential

Membrane potential – Membrane potential – the difference in the difference in electrical charge electrical charge between the inside between the inside and outside of a cell.and outside of a cell.

1)1) The tip of one The tip of one electrode is electrode is positioned outside positioned outside the neuron.the neuron.

2)2) The tip of a fine The tip of a fine microelectrode microelectrode (1/1,000 mm) is (1/1,000 mm) is advanced until it advanced until it pierces the pierces the membrane and is membrane and is positioned inside the positioned inside the neuron.neuron.

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Resting Membrane PotentialResting Membrane Potential

Resting potential is -70 mVResting potential is -70 mVThe inside of the neuron is 70 The inside of the neuron is 70

mV less than the outside mV less than the outside (extracellular fluid).(extracellular fluid).

The neuron is said to be The neuron is said to be polarizedpolarized – a -70 mV charge is – a -70 mV charge is built up across the built up across the membrane.membrane.

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Ionic Basis of the Resting Ionic Basis of the Resting PotentialPotential

Cl-Cl-

Cl-

Cl-Cl-

Cl- Cl-Cl-

Cl-

Cl-

K+ K+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+ Na+Na+

Na+

Na+

Na+

Na+

Ions are charged particles. There Ions are charged particles. There are more negative ions relative are more negative ions relative to positive ones inside the to positive ones inside the neuron. This is due to the neuron. This is due to the interaction of 4 factors (2 act to interaction of 4 factors (2 act to distribute ions evenly and 2 are distribute ions evenly and 2 are features of the cell membrane):features of the cell membrane):

1)1) Random motionRandom motion - particles in - particles in constant motion move down their constant motion move down their concentration gradientsconcentration gradients..

2)2) Electrostatic pressureElectrostatic pressure – like – like charges repel, opposites attract.charges repel, opposites attract.

• No single class of ions is No single class of ions is distributed evenly across both distributed evenly across both sides of the cell membrane.sides of the cell membrane.

• Sodium (NaSodium (Na++) and chloride (Cl) and chloride (Cl--) ) are greater outside.are greater outside.

• Potassium (KPotassium (K++)) and large protien ions (Anions; A--) are greater inside.

A--

A--

A--

A--

A-- A--

A--

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Ionic Basis of the Resting Ionic Basis of the Resting PotentialPotential

Cl-Cl-

Cl-

Cl-Cl-

Cl- Cl-Cl-

Cl-

Cl-

K+ K+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+ Na+Na+

Na+

Na+

Na+

Na+

3)3) Differential permeabilityDifferential permeability – The – The membrane has specialized pores membrane has specialized pores called ion channels for each kind called ion channels for each kind of ion.of ion.

• Potassium (K+) and chloride (ClPotassium (K+) and chloride (Cl--) ) ions pass readily through their ions pass readily through their channels.channels.

• Sodium (NaSodium (Na++)) ions pass through with difficulty.

• Large protien ions (A--) are trapped inside.

IF some ions can pass through the membrane then what prevents them from flowing down their concentration gradients?

IS it electrostatic pressure?

A--

A--

A--

A--

A-- A--

A--

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Hodgkin & Huxley (1950)Hodgkin & Huxley (1950)

Cl-Cl-

Cl-

Cl-Cl-

Cl- Cl-Cl-

Cl-

Cl-

K+ K+

K+

K+

K+

K+

K+

K+

K+

Na+

Na+

Na+ Na+Na+

Na+

Na+

Na+

Na+

To answer the question To answer the question Hodgkin & Huxley Hodgkin & Huxley calculated the calculated the amount of amount of electrostatic charge electrostatic charge that would be that would be required for each ion required for each ion that can pass that can pass through the through the membrane (Cl-, K+ membrane (Cl-, K+ and Na+) to move and Na+) to move down their down their concentration concentration gradients.gradients.

A--

A--

A--

A--

A-- A--

A--

70 mV from CG

70 mV from ES

90 mV from CG

70 mV from ES

50 mV from CG

70 mV from ES

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Hodgkin & Huxley (1950)Hodgkin & Huxley (1950)

Concluded that there are Concluded that there are active mechanisms in the cell active mechanisms in the cell membrane to counteract the membrane to counteract the passive influx (inflow) of Na+ passive influx (inflow) of Na+ ions and the passive efflux ions and the passive efflux (outflow) of K+ ions.(outflow) of K+ ions.

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Sodium-Potassium PumpSodium-Potassium Pump

4)4) Subsequently it was Subsequently it was discovered that the discovered that the sodium-potassium sodium-potassium pumppump exchanges 3 exchanges 3 sodium ions out of the sodium ions out of the neuron for every 2 neuron for every 2 potassium ions potassium ions brought into the brought into the neuron. This is an neuron. This is an active mechanism that active mechanism that requires energy (ATP) requires energy (ATP) to maintain the resting to maintain the resting membrane potential.membrane potential.

NaNa++NaNa++NaNa++

KK++

KK++

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How do neurons talk to each How do neurons talk to each other?other?

When one neuron fires an action When one neuron fires an action potential, it causes the release of potential, it causes the release of neurotransmitter molecules into the neurotransmitter molecules into the small space that separates the terminal small space that separates the terminal bouton from the receptive portion of bouton from the receptive portion of the neuron (e.g., a dendritic spine). the neuron (e.g., a dendritic spine). The space is called the The space is called the synapsesynapse..

Neurotransmitter molecules bind to Neurotransmitter molecules bind to receptors on the next neuron, causing receptors on the next neuron, causing one of two events.one of two events.

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Two Postsynaptic EventsTwo Postsynaptic Events

DepolarizationDepolarization – decreases the – decreases the resting membrane potential (e.g., resting membrane potential (e.g., from -70 to -67 mV).from -70 to -67 mV).

HyperpolarizationHyperpolarization – increases the – increases the resting membrane potential (e.g., resting membrane potential (e.g., from -70 to -72 mV).from -70 to -72 mV).

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Postsynaptic Potentials Postsynaptic Potentials (PSPs)(PSPs)

Depolarizations are called Depolarizations are called Excitatory Excitatory postsynaptic potentials (EPSPs)postsynaptic potentials (EPSPs) – – they increase the likelihood that the they increase the likelihood that the postsynaptic (receiving) neuron will postsynaptic (receiving) neuron will itself generate an action potential.itself generate an action potential.

Hyperpolarizations are called Hyperpolarizations are called Inhibitory postsynaptic potentials Inhibitory postsynaptic potentials (IPSPs)(IPSPs) – they decreases the – they decreases the likelihood that the postsynaptic neuron likelihood that the postsynaptic neuron will generate an action potential.will generate an action potential.

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Postsynaptic Potentials Postsynaptic Potentials (PSPs)(PSPs)

Both EPSPs and IPSPs are Both EPSPs and IPSPs are graded eventsgraded events – i.e., the – i.e., the amplitudes of both PSPs are amplitudes of both PSPs are proportional to the intensity of proportional to the intensity of the signal (they come in different the signal (they come in different sizes).sizes).

Weak signals generate small Weak signals generate small PSPs and strong signals elicit PSPs and strong signals elicit large PSPs.large PSPs.

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Postsynaptic Potentials Postsynaptic Potentials (PSPs)(PSPs)

PSPs travel passively from the PSPs travel passively from the site of origin, similar to the way site of origin, similar to the way an electrical signal travels an electrical signal travels through a cable.through a cable.

Accordingly, PSPs travel fast but Accordingly, PSPs travel fast but are are decrementaldecremental (i.e., they (i.e., they decrease in amplitude the decrease in amplitude the further they travel).further they travel).

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Integration of PSPs and Integration of PSPs and Generation of Action Potentials Generation of Action Potentials

(APs)(APs) In order to generate an AP (making a In order to generate an AP (making a

neuron “fire”) the neuron “fire”) the threshold of threshold of excitationexcitation must be reached at the must be reached at the beginning section of the axon, near beginning section of the axon, near the axon hillock.the axon hillock.

Integration of IPSPs and EPSPs must Integration of IPSPs and EPSPs must result in a potential of about -65mV result in a potential of about -65mV in order to generate an APin order to generate an AP

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IntegrationIntegration

Adding or combining a number of Adding or combining a number of individual signals into one overall individual signals into one overall signal.signal.

Temporal summationTemporal summation – – integration of events happening integration of events happening at different times.at different times.

Spatial summationSpatial summation - integration - integration of events happening at different of events happening at different places.places.

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Spatial Spatial SummationSummation

Local PSPs Local PSPs produced produced simultaneously simultaneously on different on different parts of the parts of the neuron sum to neuron sum to produce produce greater PSPs greater PSPs or cancel each or cancel each other out. other out.

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Temporal Temporal SummationSummation

PSPs produced PSPs produced in rapid in rapid succession at succession at the same the same synapse sum synapse sum to form a to form a greater signal.greater signal.

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Comparison of Comparison of PSPs and APsPSPs and APs

In contrast to PSPs, In contrast to PSPs, the AP is a massive the AP is a massive mommentary mommentary reversal of the reversal of the membrane potential membrane potential from -70 mV to +50 from -70 mV to +50 mV.mV.

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Comparison of PSPs and APsComparison of PSPs and APs

EPSPs/IPSPsEPSPs/IPSPs APsAPsGraded events – they Graded events – they come in different come in different sizessizes

All-or-none – like All-or-none – like firing a gunfiring a gun

Not propagated – Not propagated – they travel by they travel by passive cable passive cable propertiesproperties

Propagated – once Propagated – once they begin they they begin they travel all the way travel all the way down the axondown the axon

Decremental – the Decremental – the farther they go the farther they go the weaker the getweaker the get

Nondecremental – Nondecremental – the height is the the height is the same from beginning same from beginning to endto end

2121

Sodiu

mch

annel

Na+

K+

A--

Na+Na+

Na+

Na+

Na+

Na+

A--A--

A--

A--K+

K+

K+

K+

Cl-

Cl-Cl-

Cl-

Cl-

+

-

+

-

+

-Pota

ssiu

mch

annel

K+

K+

Sodiu

mch

annel

K+

+

-

+

-

+

-

Na+ Na+

Sodiu

mch

annel

Na+

Ionic Basis of the APIonic Basis of the AP

2222

Ionic Basis of the APIonic Basis of the AP

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Refractory PeriodsRefractory Periods

Absolute refractoryAbsolute refractory – a brief – a brief period (1-2 ms) after the initiation period (1-2 ms) after the initiation of an AP during which it is not of an AP during which it is not possible to elicit another AP.possible to elicit another AP.

Relative refractoryRelative refractory – the period – the period in which it is possible to fire an AP, in which it is possible to fire an AP, but only if higher-than-normal but only if higher-than-normal levels of stimulation are applied.levels of stimulation are applied.

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Refractory PeriodsRefractory Periods

Refractory periods are Refractory periods are responsible for two responsible for two characteristics of neural characteristics of neural conduction:conduction:

1.1. APs normally travel in one APs normally travel in one direction.direction.

2.2. Rate of neural firing is Rate of neural firing is related to the intensity of related to the intensity of the stimulation.the stimulation.

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Saltatory ConductionSaltatory Conduction

Transmission of APs in myelinated Transmission of APs in myelinated axons – axons – saltaresaltare (to “skip” or (to “skip” or “jump”).“jump”).

AP conduction along myelinated AP conduction along myelinated segments of an axon is passive.segments of an axon is passive.

i.e., it travels fast but gets i.e., it travels fast but gets weaker the farther it goes.weaker the farther it goes.

The signal is still strong enough The signal is still strong enough to generate a full AP at the next to generate a full AP at the next node.node.

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How fast are APs?How fast are APs?

Conduction speed depends on:Conduction speed depends on:

1.1. Diameter of axon (faster in Diameter of axon (faster in large axons).large axons).

2.2. Myelination (faster in Myelination (faster in myelinated axons).myelinated axons).

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Conduction in Myelinated Conduction in Myelinated AxonsAxons

Passive movement of AP within myelinated Passive movement of AP within myelinated portions occurs instantlyportions occurs instantly

Nodes of Ranvier (unmyelinated)Nodes of Ranvier (unmyelinated)– Where ion channels are foundWhere ion channels are found– Where full AP is seenWhere full AP is seen– AP appears to jump from node to nodeAP appears to jump from node to node

Saltatory conductionSaltatory conduction http://www.brainviews.com/abFiles/AniSalt.htm

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The Changing View of Dendritic The Changing View of Dendritic FunctionFunction

Three recently discovered Three recently discovered characteristics of dendrites:characteristics of dendrites:

1.1. Some can generate APs that travel in Some can generate APs that travel in either direction.either direction.

2.2. Dendritic spines restrict chemical Dendritic spines restrict chemical changes to the immediate area of the changes to the immediate area of the synapse (they compartmentalize the synapse (they compartmentalize the dendrite).dendrite).

3.3. Spines change rapidly (within Spines change rapidly (within minutes to hours) in shape and minutes to hours) in shape and number in response to neural number in response to neural stimulation.stimulation.

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Overview of Neural signalsOverview of Neural signals

1)1) EPSPs and IPSPs (PSPs) are graded events EPSPs and IPSPs (PSPs) are graded events initiated by the action of neurotransmitters initiated by the action of neurotransmitters binding to receptors on the postsynaptic binding to receptors on the postsynaptic membrane.membrane.

2)2) PSPs summate spatially and temporallyPSPs summate spatially and temporally3)3) If EPSP signals are greater, causing a If EPSP signals are greater, causing a

change in membrane potential change in membrane potential (depolarization) to -64 mV (threshold of (depolarization) to -64 mV (threshold of exitation) at the beginning segment of the exitation) at the beginning segment of the axon, then the postsynaptic neuron will fire axon, then the postsynaptic neuron will fire an APan AP

4)4) Once initiatiated the AP travels the full Once initiatiated the AP travels the full length of the axon to the terminal buttons. length of the axon to the terminal buttons.