What is an Action Potential? Break Down: Resting Membrane Potential AP Generation Signal Propagation Neurotransmitter Release Signal Received (EPSP/IPSP) Repeat The arrival of an action potential at the terminal will cause calcium, Ca+, to enter the cell and release vesicles filled with neurotransmitter. vesicle neurotransmitters exocytosis Synapse Receptor Release of neurotransmitter will produce a change along the post-synaptic membrane of the next neuron in the chain …and so on… Neurotransmitter Receptor (ion channel) • Neurotransmitter engages a receptor (lock-and-key) • Receptor may be an ion channel • If it opens an ion channel… EPSP Sodium ion flow inward is responsible for the generation of an EPSP. IPSP Chloride ion flow inward is usually responsible for the generation of an IPSP Synaptic Release (Movie) Multiple Inputs Post-synaptic membrane may receive an excitatory postsynaptic potential (EPSP) and become depolarized or Post-synaptic membrane may receive an inhibatory postsynaptic potential (IPSP) and become hyperpolarized or BOTH Multiple excitatory and inhibitory inputs onto dendrites and the soma summate. Spatial Summation EPSP summation is decrimental- it is proportional to input Temporal Summation Temporal and Spatial Summation (Movie) Summary • Neurotransmitter released causes change in ion permeability on postsynaptic membrane. • Depending on ion, causes an EPSP or IPSP • EPSPs and IPSPs are summated spatially and temporally Summary - Action Potential •Initially the cell is resting at around -70 mV. •Cell receives EPSPs and IPSPs from other neurons. •The cell becomes excited (depolarized) enough… •Threshold (-55 mV) is reached, voltage-gated Na+ channels open and action potential is sent down axon from the axon hillock. •Inward rush of Na+ depolarizes adjacent area of axon and preps new AP site. •The AP peaks (+35 mV), Na+ channels close and voltageactivated K+ channels open. •K+ efflux follows Na+ influx down the axon and causes hyperpolarization that prevents the AP from traveling backwards. •AP reaches axon terminal. Ca+ enters and releases vesicles filled with neurotransmitter. •NT crosses the synapse and binds receptor on post-synaptic cell Review Good animated review at http://outreach.mcb.harvard.edu/animations/actionpotential.swf What is a membrane potential? -difference in voltage across the membrane What is the value of the RMP of a neuron? -it’s -70mV What inside the cell is large, immobile, and negative? -proteins, AWhat does selective permeability mean? is different from positive ion ion . is negative. and negative Which way is concentration force of Which way is electrical force of ? ? Define the Chemical and Electrical forces on these ions in a neuron at RMP (-70inside) More Concentration Electrical concentrated gradient pushes gradient on the… it… pushes it… Cl- Outside IN OUT K+ Inside OUT IN Na+ Outside IN IN Determine Chemical and Electrical forces on K+ at different membrane potentials (*remember it’s still highly concentrated on the inside) Chemical Electrical force pushes force pushes it… it… At RMP (-70 mV) OUT IN At peak (+35 mV) OUT OUT Depolarize or Hyperpolarize? Membrane potential travels from -70 → -55 Depolarize Membrane potential travels from -70 → 10 Depolarize Membrane potential changes from -70 → -80 Hyperpolarize Na+ enters cell Depolarize Negative Cl- enters resting cell (-70) Hyperpolarize What Phase? EPSPs Return to Rapid RMP Repolarization (generator Threshold Hyperpolarization RMP Depolarization potential) What channels are open? Which ions are moving? Which direction? Na+/K+ non-v-gated pump working and v-gated (Na+ K+ K+ K+ Na+ leak OUT OUT IN ↨ out and Na+K+ IN in) The permeability (leaking) of which ion is proportional to the RMP K+ Which ion enters the cell, depolarizes the membrane and starts the AP Na+ Which ion repolarizes the membrane by leaving the cell K+ Hyperpolarization is the function of which ion channels remaining open K+ What channel/pump maintains and reestablishes the RMP? Na+/K+ pump • K+ leaks out across the membrane more easily than Na+ leaks in • The Na+/K+ pump trades 3 Na+ for 2 K+, does this really restore balance? • Yes, because the neuron does not stay at RMP for long, it will fire APs, and eventhough there is an efflux of K+ from the neuron, there is so much Na+ influx that a 3:2 by the pump restores the correct balance. True or False Ion distribution at resting in the axon is like that of the dendrites and soma. TRUE Electrical and chemical gradients act differently on ions in the axon than in the soma. FALSE K+ efflux follows Na+ influx as it proceeds down the axon. TRUE Na+ starts entering the next site while K+ is hyperpolarizing the old site. TRUE Myelination pushes the field of depolarization from Na+ entry further than it would go in an unmyelinated axon. TRUE In saltatory conduction, the depolarization jumps over the outside of the myelin. FALSE Na+ is already depolarizing the next node while K+ is beginning to efflux. TRUE An AP starts out at full force and gets weaker as it travels down the axon. FALSE Depolarization from Na+ is not localized, but also effects nearby membrane. What does it do there? What is the importance? Depolarizes neighboring membrane to threshold so that it opens v-gated Na+ channels and fires AP next. If you put an electrode into the middle of an axon and stimulate (depolarized it), the AP would go in what direction? Why? Both. There wouldn’t be any hyperpolarization from K+ efflux following it until after the AP is started by the electrode. Entry of which ion besides Na+ is important for release of vesicles containing neurotransmitter? Calcium, Ca+ Name two ways in which EPSPs and IPSPs summate Temporal and spatial If there are enough EPSPs, what happens? An AP is sent from the axon hillock. EPSP or IPSP? GABA receptor lets Cl- into cell IPSP Ach receptor lets Na+ into the cell EPSP Ach receptor lets Ca+ into the cell EPSP Glycine receptor lets Cl- into the cell IPSP A different GABA receptor causes K+ to leave the cell IPSP Be able to… Determine which direction K+, Na+, and Cl- would travel at various membrane potentials (ex. -70, -55, 0, 30) Describe which ions are moving and why at each stage of the AP Predict change in AP profile under influence of neurotoxins (Ex. TTX that blocks v-gated Na+, a toxin that blocks K+ efflux) Predict the effect of a neurotransmitter on the postsynaptic membrane, ie EPSP or IPSP (Ex. Ach → NA+ influx and GABA →Cl- influx) 699 Research Our Guidance Office is spectacular Psych >Undergrad >Research >link to research opportunities or ask a Prof • Gain experience before grad school or employment. • Great on resume! • Great letters of rec. • Honors thesis