Synaptic plasticity Flashcards
Learning
Learning is the response of the brain to environmental events and involves adaptive changes in synaptic connectivity which will in turn alter behaviour.
Hebb’s cell assembly
- Reciprocal connections between neurons
- Stimulus = Activation of cell assembly by stimulus
- Reverberating activity continues after stimulus removed
- Hebbian modification strengthens reciprocal connections between neurons that are active together
- The strengthened connections contain engram of stimulus
- After learning, partial stimulus of the cell assembly leads to activation of the entire representation of the stimulus.
Hebb’s rule
- ’ Neurons that fire together, wire together’
- ‘Neurons that fire out of sync, lose their link’
Long-term potentiation
= Mechanism underlying synaptic strengthening
- High frequency stimulation = Long-term potentiation lasts hours.
- Multiple high frequency stimulations = LTP can last days/months.
LTP characteristics
- Temporal = Summation of inputs reaches threshold that leads to induction of LTP e.g. Repetitive stimulation (HFS)
- Associative = Simultaneous stimulation of strong and weak pathways will induce LTP at both pathways. ‘ Cells that fire together, wire together’.
- Specific = LTP at one synapse is not propagated to adjacent synapses.
What happens at the synapse? (1) Inactive cell
- Glutamate release onto inactive cell
- AMPA receptor activated = Excitatory post synaptic potential.
- NMDA receptor blocked by mg2+
- Depolarisation from AMPA not sufficient to expel mg2+
What happens at the synapse? (2) Active cell
- Glutamate released onto active cell (membrane already depolarised)
- AMPA receptor activated
- mg2+ released from NMDA
- Na+ through AMPA + NMDA
- Ca2+ through NMDA
What happens at the synapse (3)
Ca2+ entry through NMDA leads to:
- Activation of PKC
- Activation of CamKII
Results in:
- Phosphorylation of AMPA = Increased effectiveness
- Insertion of new AMPA receptors into membrane.
= More AMPA channels working more effectively = Larger excitatory post synaptic potentials and LTP
CamKII = Molecular switch
- Ca2+ entry through NMDA leads to activation of CamKII.
- CamKII has autocatalytic activity and becomes phosphorylated
- Once phosphorylated, becomes constitutively active and no longer requires Ca2+.
- Maintains phosphorylation, insertion of AMPA etc after stimulus removed.
- Therefore, is a molecular switch that maintains excitability for minutes to hours.
Presynaptic events in LTP
- Postsynaptic cell can feedback to presynaptic cell via nitric oxide.
- Ca2+ through NMDA activates NO synthase.
- NO diffuses and activates guanylyl cyclase in presynaptic cell
- Guanylyl cyclase actuvated cGMP.
- Signal transduction cascade leads to increased glutamate release
Late phase LTP
- Protein synthesis required for long-lasting LTP (Days, months) = Gene transcription
- Protein synthesis inhibitors prevent consolidation of LTM
- Creb 2 = No transcription
- Creb 1 replaces Creb 2 and when it is phosphorylated by CamK11 and PKA, gene transcription can occur.
Early vs late phase LTP
Early:
- Ca2+ through NMDA and subsequent enhancement of AMPA efficiency and increased number of AMPA + presynaptic events.
Late:
- New protein synthesis, morphological changes and establishment of new synapses.
- Ca2+ stimulates new gene transcription (CREB mediated)
Long term depression
- Low frequency stimulation results in LTD
- Leads to decrease in EPSP amplitude
- Activates phosphates
- AMPA receptors are dephosphorylated and removed from membrane
LTP and LTD
Reflect bidirectional regulation of:
- Phosphorylation
- Number of postsynaptic AMPA receptors
Evidence
NMDA receptor activation in Hippocampus is essential for LTP and spatial learning
AP5 = NMDA receptor antagonist
- blocks hippocampal learning
- blocks learning in water maze
also replicated in human brains
- HFS = LTP
- LFS = LTD
