BMS248 Lecture 10/11 - LTP + LTD Flashcards
What is a Hebbian synapse?
A synapse that increases in effectiveness/strength because of simultaneous activity in pre and postsynaptic neurons
What area of the brain is primarily involved in memory formation? (particularly spatial)
The hippocampus
What is the pathway of the hippocampal circuit?
. Entorhinal cortex to Dentate gyrus - via perforant pathway
2. Dentate gyrus to CA3 - via Mossy fibres
3. CA3 to CA1 - via Schaffer collaterals
4. Output via Fornix + Subiculum
What is the pathway of the hippocampal circuit?
- Entorhinal cortex to Dentate gyrus - via perforant pathway
- Dentate gyrus to CA3 - via Mossy fibres
- CA3 to CA1 - via Schaffer collaterals
- Output via Fornix + Subiculum
What is LTP?
Persistent strengthening of synapses that leads to long-lasting increase in signal transmission between neurons - via high frequency stimulus
INCREASE IN EPSP
What is LTP?
Persistent strengthening of synapses that leads to long-lasting increase in signal transmission between neurons - via high frequency stimulus
INCREASE IN EPSP
Where does LTP occur? What kind of synapse is this?
CA3 to CA1 synapses - via Schaffer collaterals
Glutamatergic synapse
How does LTP show input specificity?
Restricted to activated synapses rather than all the synapses on a given neuron
How does LTP show co-incidence?
Two pathways converging on the same target can both be strengthened if they fire together (greater EPSP) - does not require HFS
What are the 3 types of glutamate receptors?
- NMDAR - increase in Ca2+ at postsynaptic neuron
- AMPAR - depolarises postsynaptic neuron (Na+ and K+)
- mGluR - GPCR
Co-operativity is a result of what kind of block on NMDA receptors and how?
Voltage dependent Mg2+ block - the receptor needs to be indirectly pre-activated by a separate depolarising input (requires glutamate and depolarisation)
Co-operativity is a result of what kind of block on NMDA receptors and how?
Voltage dependent Mg2+ block - the receptor needs to be indirectly pre-activated by a separate depolarising input (requires glutamate and depolarisation)
What is activated in early phase LTP by NMDAR (induction)?
- NMDAR allows influx of Ca2+
- This activates CaMKII (calmodulin kinase II)
- Autophosphorylation of CaMKII - goes on to phosphorylate other proteins
- Constant activation triggered by Ca2+ during LTP
Phosphorylation by CaMKII enhances what and how?
AMPA currents - amplitude of current increases (greater EPSP) - this occurs by AMPAfication (greater no of AMPA receptors delivered to the postsynaptic neuron)
What is the result of late phase LTP (expression)?
Change in gene expression and therefore the protein synthesis - takes effect 1hr after initiation
What signalling is responsible for late phase LTP?
cAMP signalling
How does the change in gene expression in late phase LTP occur?
- cAMP activates PKA - which translocates to nucleus
- In the nucleus it phosphorylates CREB complex
- This replaces inactive CREB-2, with active phosphorylated CREB-1
- Leading to the initiation of transcription by CRE transcription factor
What kind of proteins are produced by late phase LTP?
Channels/proteins that translocate to the PSD - this increases amplitude of EPSP
Knockout/mutation of CaMKII, NMDARs, cAMP pathway have what effect?
Effect aspects of learning/memory - LTP is only necessary but not sufficient for some memory formation
What is the Cerebellar LTD circuitry and how does LTD occur?
- Paired climbing fibre and parallel fibre onto a single Purkinje cell
- Stimulate both at same time: get a decrease in EPSP - requires co-incidence
- This is input specific (like in LTD)
What receptors do climbing fibres and parallel fibres possess?
- Climbing fibres use AMPAR
- Parallel fibres use AMPAR + mGluR
What is the mechanism of Cerebellar LTD?
- Ca2+ entry leads to activation of PKC
- This phosphorylates GluR2 subunit (different to LTP) of AMPA receptors on parallel fibre
- Leads to a decrease in the number of receptors by endocytosis - internalisation
- Reduced current - reduced EPSP
Inhibitors of what prevent LTD?
Endocytosis
Where does LTD take place in the Hippocampus?
CA3 to CA1 synapse with low frequency stimulation (LTP - high frequency)
What is depotentiation?
Reversal of a previous LTP
What is depotentiation?
Reversal of a previous LTP
The amount of what receptor activation determines the probability of inducing LTP or LTD, and why?
The amount of NMDA receptor activation:
LTP - HFS - high receptor activation
LTD - LFS - low receptor activation
What is the mechanism of Hippocampal LTD?
- Low frequency stimulation
- Low levels of NMDAR
- Low levels of CA2+
- Phosphatase activation (rather than kinase in LTP)
- Reduction in AMPAR efficacy
- Less current - reduction in EPSP
