Module 3, lecture 2 Flashcards
Hebbian plasticity
proposed that coordinated activity of a pre and postsynaptic neuron strengthens the connection between them (neurons that fire together, wire together)
what is co-activation (hebbian plasticity)
Implies the involvement of a coincidence detector (neuron or molecular mechanism that responds specifically when two or more inputs arrive at the same time (or within a narrow time window))
- widely assumed to be the neural basis of associative learning and memory
-also important for activity-dependent refinement of neural connections during development and recovery from injury (Neural circuits in the brain and nervous system are not fully “pre-wired”—they get shaped and fine-tuned based on experience and activity)
Long-term Plasticity at Hippocampal Synapses:
Long-term potentiation (LTP)
Long-lasting increases in synaptic strength due to certain patterns of synaptic activity (enhancement)
post synaptic level changes
Long-term Plasticity at Hippocampal Synapses:
Long-term depression (LTD)
Long-lasting decreases in synaptic strength due to certain patterns of synaptic activity. (decrease)
post synaptic level changes
LTP at a Hippocampal Synapse: Brief high-frequency train of stimuli (tetanus)
Long-lasting increases in EPSP amplitude = LTP
-> synapse/input specific: LTP is induced in active/stimulated synapse only
-> Cellular basis for information storage (memory formation)
LTP at a Hippocampal Synapse: Weak stimulation of one pathway
no LTP
-Strong/tetanus depolarization of post-synaptic membrane at the same time of weak stimulation → LTP (equivalent to weak stimulus to one terminal + strong stimulus to another) –> both LTP
-Associativity (pre and post synaptic cell: co-activation, if depolarized at the same time = LTP)
Cellular basis for associative learning
Molecular Mechanism of hippocampal LTP
NMDA-R (ionotropic Glu receptor, blocked by Mg) = molecular coincidence detector (need unblockage from strong depol. And Glu release from weakly stimulated presynaptic terminal)
- Tetanus/strong stimulus unblocks channel (release of M2+) in post- synaptic cell
- Pre-synaptic Glu release → opening of channel
Fast and large increase in postsynaptic Ca2+ (influx through NMDA-R) → induction of LTP
Molecular Mechanism of hippocampal LTP: Expression of early phase
Mediated by:
(trafficking of AMPA receptors) of LTP - (1- 2h) depends on insertion (caused by Ca2+ influx) of AMPA Rs stored in endosomes (on postsynaptic membrane)
Glu activates more AMPA -> more depolarization -> more EPSP
Mediated by:
- Synaptotagmin
- CAMKII
- PKC
Molecular Mechanism of hippocampal LTP: Expression of late* phase (maybe* if stimulus lasts long enough) of LTP (h-days)
relies on gene expression and protein synthesis (synthesize more AMPA receptors)→ Synapse growth
Mediated by:
- cAMP-dep activation of PKA and CREB (transcription factors for specific genes, more AMPA)
AMPA-R Trafficking and the Awakening of Silent Synapses (no post synaptic activation/response)
- In mature brain
- Stimulation of some Glu synapses in early post-natal stage -> no APs
- only NMDA Rs present and blocked by Mg2+ = silent synapse
-In adulthood: also AMPA Rs present
- Depolarization of postsynaptic neuron via AMPA Rs displaces Mg2+ –> active synapse
Long-term Depression (LTD) in the Hippocampus
-When the Schaffer collaterals are stimulated at a low frequency (1 Hz) for 10-15 mins -> depresses EPSP → LTD (decrease in postsynaptic response)
- Can reverse the effects of LTP (and vice-versa)
- Input-specific and associative
Molecular Mechanisms of Hippocampal LTD
-Caused by small and slow rise in [Ca2+]i.
-Associated with activation of phosphatases and loss of AMPA Rs (probably due to internalization by endosomes). lower response, less depolarization
-Late phase → protein synthesis less Ca2+ enters, depression not enhancement -> endocytosis of AMPA receptors
Long-term depression (LTD) in the Cerebellum (one of the first places discovered)
Purkinje neurons receive 2 excitatory inputs: parallel and climbing fibers.
LTD decreases the strength of transmission at the parallel fiber (and climbing fiber synapses).
→ Cellular mechanism for associative (motor) learning
