Synaptic Plasticity Flashcards
What does synaptic plasticity refer to?
increases or decreases in synaptic strength in response to patterns of synaptic activity
How do we measure synaptic strength?
Membrane currents
Potential
Describe facilitation
- 2 spikes close together in the pre-synaptic membrane, the second spike elicits greater post-synaptic potential than the first did
- This is because Ca2+ is still present in the synaptic terminal, higher IC Ca2+ conc, larger vesicluar release (as vesicles dependent on Ca2+)
- As you increase the time interval between spikes the facilitation decreases because Ca2+ conc returns to normal
Describe depression
- Longer runs of spikes result in post synaptic response decreasing in size
- Vesicle depletion is occurring
- Can’t recycle fast enough
Where is a key area of LTP and LTD? Why do we think this?
• Hippocampus is the key place studied:
o fMRI activated during memory tasks
o Lesions impair memory formation
o Rodent ‘place cells’ identified that only fire in specific locations – memory of locations
o Lesions in hippocampus affect spatial learning tasks
Describe the tri-synaptic circuit of the hippocampus
- Projection from entorhinal cortex
- To dentate gyrus
- To CA3 field
- Synapse to CA1 field via long Schafer collaterals – this is the synapse mainly studied
What experiment shows the LTP of SC-CA1 synapse
- Separate the pathways into ‘pathway 1’ and ‘pathway 2’
- Stimulate pathway 1 with high frequency stimulation (tetanus), not pathway 2
- LTP occurs in pathway one for about an hour
- No LTP in pathway 2
What are the basic properties of LTP?
- Cooperative – need a strong input to activated it, a crucial number of fibres simultaneously activated
- Input specificity – synapse must be activated during induction – other pathways don’t effect it, must be the specific synapse
- Associativity – induction at concurrently active synapses (Hebb’s Law – cells that fire together, wire together)
What is the role of AMPA receptors in the mechanism of LTP?
AMPA receptors:
• Mainly AMPA receptor facilitated – increase number of AMPA receptors on post-synaptic membrane, increase response in post-synaptic membrane:
• Large, fast ↑ Ca2+ in post-synaptic membrane
• Kinase activation
• Insertion of additional AMPAR into post synaptic membrane (often from other areas of the cell membrane)
• Retrograde signalling
→ presynaptic changes (later)
• This process requires lots of other processes e.g. protein phosphorylation, cytoskeletal reorganisation and local protein synthesis
What is the role of NMDA receptors in LTP?
NMDA receptors:
• Also induction of LTP is NMDA receptor-dependent
• High frequency stimulus → prolonged depolarization leading to alleviation of Mg2+ block on NMDA receptors
• Allows Na+ and Ca2+ influx – can be associative
• This mechanism can be blocked by by Ca2+ chelators – also blocks LTP
What is the role of remodelling of dendritic spines during LTP?
- Short time scale for remodelling, lasts long time
* Actin cytoskeleton remodels, grows dendritic spines
What is the role of gene transcription during LTP?
Late phase LTP involves gene transcription via CREB:
• Requires retrograde transport
• Kinase cascades needed for affecting gene transcription
What is LTD induced by?
- Induced by prolonged low frequency stimulation e.g. 1Hz 10-15 mins
- Leads to small & slow ↑ Ca2+ levels IC
- Causes phosphatase activation e.g. calcineurin (induction of LTD but not LTP sensitive to phosphatase inhibitors)
- Dephosphorylation of stargazing occurs causing endocytosis of AMPAR
Describe the role of LTD in the cerebellum
• Paired stimulation of Climbing Fibres and Parallel Fibres causes LTD that decreases Purkinje Cell EPSP:
o Climbing fibres synapse many times but all onto one Purkinje cell only
o Also synapse onto granule cells which has parallel fibres
o When the climbing fibre activates it sends signals to the purkinje cell and the parallel fibres (via the granule cells) together:
Glu release from parallel fibre activates mGluR
Climbing fibre activation (strong) depolarises purkinje cell, opens VGCC (co-activation from 2 different cells is important)
Synergistic activation of PKC (& MAPK)
Internalisation of AMPA receptors
o This causes LTD which decreases the purkinje cell EPSP
• May be important for motor learning
What are the pre-synaptic changes in LTP and LTD?
- Effects on NT release machinery to increase vesicular release or increase VGCC - LTP
- Retrograde transport of cannabinoids from the post synaptic membrane to pre-synaptic membrane to decrease pre-synaptic NT release – LTD
