How Synapses Integrate Information and Change Rachel Stewart class of 2016 https://nba.uth.tmc.edu/neuroscience/s1/chapter06.html https://nba.uth.tmc.edu/neuroscience/s1/chapter07.html Chris Cohan, Ph.D. Dept. of Pathology/Anat Sci University at Buffalo
Learning Objectives 1. Describe how postsynaptic potentials differ from action potentials. 2. Describe how synapses integrate activity from multiple presynaptic inputs. 3. Describe the role of presynaptic Ca in short term changes in synaptic strength. 4. Describe how the NMDA receptor works 5. Discuss how NMDA receptors are involved in LTP and how it influences changes in synaptic function.
NT Binding - Chemical to Electrical Signaling Postsynaptic potential created when Neurotransmitter binds to postsynaptic ionotropic receptor: excitatory - EPSP Vrest inhibitory - IPSP Vrest Properties: sign - determined by receptor graded in amplitude # vesicles released affects size Sum algebraically to allow integration of information electrical properties of postsynaptic membrane (V=IR) slower than APs why (more time for integration)
Synaptic Integration NS integrates info by algebraic summing of PSPs: temporal summation PSPs from 1 terminal close in time (eg E1 + E1) spatial summation PSPs from 2 terminals close in time (eg E1 + E2) Action potential frequency depends on sum of total synaptic activity. E1 resultant EPSP summation EPSP + IPSP summation
Position of Synaptic Terminals on Dendrite Synaptic terminals on dendrites farther from cell body have less effect on action potential initiation. Potentials get smaller with distance they travel along dendrite AP initiation zone -Summing point for PSPs
Reality The pattern of action potentials in neurons is determined from moment to moment by the probability of synaptic inputs how many are active + or location frequency of activity
How Do Synapses Change Effectiveness 1. Controlling presynaptic Ca 2. Controlling # of postsynaptic receptors 3. Controlling type of postsynaptic receptor
Changes in Synaptic Function Short term changes in synaptic function are due to presynaptic Ca ++ modulation
Changes in presynaptic Ca modulate transmitter release: 1. Autoreceptor feedback Short Term Changes metabotropic receptors 2. Effect of other synapses Ca Ca influx Presynaptic inhibition # vesicles released Ca Ca Ca influx 3. Ca accumulates presynaptically when AP freq is high Presynaptic facilitation Ca # vesicles released Ca time
These integrative mechanisms allow synapses to change their effectiveness for short periods of time based on activity in the nervous system. Long term changes in synaptic effectiveness require other mechanisms.
Long Term Changes Ionotropic NMDA and AMPA glutamate receptors play essential roles in plasticity in the brain. They provide a mechanism for long term changes in synaptic function. They are also reasons for widespread neuronal death when the brain is injured.
Glutamate Receptors AMPA receptor Glu binding opens channel. Na + enters and depolarizes dendrite. produces epsp = excitatory synapse
Glutamate Receptors NMDA receptor Glu binding alone cannot open the channel because it is blocked by Mg ++ with an additional source of depolarization, Mg ++ is removed and Ca ++ and Na + flow into the cell. Ca ++ activates signaling pathways NMDA-R Ca + + Mg + + IMPLICATIONS 1. NMDAR opening requires an additional excitatory receptor/input 2. Ca ++ entry acts as a 2nd messenger to activate signaling pathways change synaptic strength. 3. Large amounts of Ca ++ enter cell if depolarization is prolonged.
Glutamate Receptors Glu + AMPA R = depolarization Glu + NMDA R = nothing! Glu + AMPA + NMDA: depolarization while Glu bound to NMDA R NMDA R now opens, causing Ca ++ influx
Glutamate Receptors Significance of Ca ++ influx through NMDA R: increase in strength of synaptic potentials lasting hours/months/years Long Term Potentiation (LTP) Mechanism: Ca ++ influx number of AMPAR large depol The increase in number of AMPA Rs causes a larger depolarization of postsynaptic cell. Maintaining LTP for long periods of time requires protein synthesis and probably involves increases in number and size of synaptic contacts (spines). before time after
LTD Long Term Depression Low level activation of a previously strengthened synapse leads to a sustained decrease in strength Long Term Depression (LTD) - loss of AMPA R before LTP LTD time
Glutamate Receptors Conclusion: LTP and LTD show how synapses can change their strength (connectivity) for long durations based on their history of activity. This is one mechanism neurons use to store and remove information about activity in the nervous system, which underlies important processes like learning, memory, and forgetting.
Glutamate Receptors In stroke, brain injury, and degenerative diseases large amounts of glutamate may be released by injured nerve terminals. This could cause a spreading wave of Ca ++ increase in neurons accompanied by neuronal death. sustained depolarization sustained AMPA + NMDAR open large Ca ++ influx Some neuroprotective measures are under study: enhancing glutamate uptake by astrocytes use of glutamate receptor antagonists (memantine)