resting potentials and action potentials lecture 10 psy391s john yeomans
TRANSCRIPT
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Resting Potentials and Action Potentials
Lecture 10
PSY391S
John Yeomans
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Special Properties of Neurons
• Excitability--Action Potential in Axons.
• Conduction--Action Potential in Axons.
• Transmission--Synapses, Electrical & Chemical.
• Integration--Postsynaptic Cell.
• Plasticity--Presynaptic Terminal and Postsynaptic Membrane.
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Resting and Action Potentials
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Pumps Exchange Ions
• All cells have pumps and resting potentials (-40 to -90 mV).
• Pumps use ATP to exchange ions.
• Na+/K+ pump: 3 Na+ exchanged for 2 K+.
• Ca++ pump: Keeps powerful Ca++ ions out.
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Concentration of Ions and State of Channels at Rest
-65 mV
Concentrations maintained by Na+/K+ and Ca++ pumps.
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Potentials
• All potentials result from ions moving across membranes.
• Two forces on ions: Diffusion (from high to low concentration); Electrical (toward opposite charge and away from like charge).
• Each ion that can flow through channels reaches equilibrium between two forces.
• Equilibrium potential for each ion determined by Nernst Equation.
• K+ make - potentials; Na+ make + potentials.
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Nernst Equation
• EK+ = +58 mV log10 ([K+] outside/[K+] inside).
(+58 mV for room temperature, squid axon).
• EK+ = 58 mV log10 1/20 = -75 mV.
• ENa+ = 58 mV log10 10/1 = + 58 mV.
• ECl- = -58 mV log10 15 = -68 mV.
• ECa++ = +58 mV log10 10,000 = +220 mV.
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Resting Potential Results from Passive K+ Channels and EK+
• At rest, membrane potential is -60 to -70 mV in most neurons. Why?
• K+ is most permeable, due to leak of K+ through passive K+ channels.
• Therefore, K+ ions leave, making the inside more negative.
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Action Potential Results from Voltage-gated Na+ Channels
ENa+ = +58 mV
EK+ = -75 mv
Closed!
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Action Potentials
• Only neurons and muscles have action potentials (not all neurons).
• Due to voltage-gated Na+ channels.• Most in axons, at initial segment (axon
hillock) and nodes of Ranvier. A few in big dendrites where depolarizations need a boost.
• Channel ionic currents are studied by voltage clamps and patch clamps.
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Voltage Clamp
• Used to measure ion currents in squid giant axons (Hodgkin & Huxley).
• Study single ion by changing ions in axon.• Hold voltage constant by injecting current with
large electrode. Measured current I.• Measured Na+ or K+ current during action
potential: INa+ = V/R = K/R ~ Na+ conductance.• Measure “channel” permeability changes.• Predicted action potential changes from Nernst
Eq and channel permeabilities.
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Single Channels
Study electrical properties,Ionic properties, Pharmacology (toxins, agonists, antagonists)Molecular biology (mutant channels)
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Voltage-gated Na++Channel: MolecularStructure and Gating
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All Na+ channels open in APabsolute refractory period.
(No voltage-gated K+ channels in mammalian unmyelinated axons)
(>1 m/s in mammals)
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(1-120 m/s)
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Synapses and Postsynaptic Potentials
Lecture 11
PSY391S
John Yeomans
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Release and Ca++
• Transmitter is synthesized and stored in vesicles.
• Action potential opens voltage-gated Ca++ channels near release sites.
• Ca++ activates proteins that move vesicles to release sites.
• Exocytosisrelease and diffusion of transmitter.• EPSPs, IPSPs (depending on ions) .• Reuptake or enzyme breakdown of transmitter.
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Chemical Receptors
Nicotinic, AMPA Na+ Muscarinic, Dopamine, GABAB
GABAA Cl- Gs, Gi
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Ionotropic Receptors
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Receptors are now defined by genes
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Second Messengers
• cAMP and cGMP, IP3, DAG (G-coupled)
• Ca++, etc.
• Kinases (dozens, e.g. A, CaMK)
• Gene transcription (CREB)
• Plasticity
• Retrograde messengers NO and CO.
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Other Receptor Types
• Steroid receptors--Lipophilic molecules pass through membrane to act in neurons.
• Tyrosine kinase receptors--NGF activates enzymes and kinases.
• Slower growth effects.
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Summation
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PSPs
• Excitatory: Na+ or Ca++ entry.
• Inhibitory: K+ efflux or Cl- entry.
• Also blocking open channels (e.g. rods and cones).
• Slow potentials: seconds to hours.
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Integration of Potentials
Lecture 12
John Yeomans
PSY391S
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Computation in Single Neurons
• Thinking requires complex computation. How?
• Neural computation occurs in postsynaptic cells, by integration of PSPs, and by changes in synapses.
• We still have no idea how thoughts are represented in neurons or circuits, only rough ideas of which brain regions are important.
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Integration in the Cell and Axon
PSPs decay with distance.
Integration occurs at axon hillock.
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Synapses on Soma, Dendrites and Spines
Thousands of synapses, of many types, on each output neuron.
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• Strongest near axon, usually inhibitory.
• Next strongest on soma and proximal dendrite shafts.
• Weakest synapses on spines, usually excitatory.
• Larger neurons usually have more synapses, more spines. Why?
Synapse Strength
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Spines
• Problem: Too many synapsestoo much ion leakage along dendrites.
• Solution: Place synapses on isolated spines.
• All spine synapse have equal access to dendrite shafts.
• Spine shapes change in minutes: mushrooms less, slivers moreplasticity.
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Plasticity
• Facilitation and depression of PSPs.• Presynaptic changes: transmitters,
vesicles, release, retrograde NO.• Postsynaptic changes: Receptors can be
added and subtracted. Channels can be phosphorylated;
• Second messengers and kinases can change postsynaptic response;
• Spines can grow or shrink; New proteins.
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Integration of Brain Potentials
• Most recordings are extracellular, or outside brain. Averages across many or millions of neurons.
• Electrode size and distance determines how many neurons are measured.
• Human studies are mainly from surface of brain. Brain-waves are correlated with thoughts (Dreams, meditation, stimuli).
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Human Potentials
• Strong potentials in muscles--EMG, ECG (electromyogram and electrocardiogram).
• Weaker potentials from brain--EEGs.
• Evoked potentials allow study of changes.
• Computer averaging allows study of deep brain potentials: Event-related potentials in sensory systems and cognition.
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EEG and ERP
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Electroencephalogram
• Shows widespread activity of brain, mainly from PSPs.
• Sleep stages, waking, slow wave, REM.
• Most intense in seizures of different types, petit mal, grand mal etc.
• Can find lobes that are most active (e.g., occipital for alpha waves, temporal or frontal lobe or for seizures).
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Event-Related Potentials
• Warning and CNV: Cortex mainly.
• I-VI : Brain stem auditory paths.
• No-P3 : Cortical processing of auditory stimulus. Primary to association areas.
• Temporal resolution better than spatial resolution.
• Brain imaging (fMRI) localizes thoughts better, but not to neurons.