L31 - 33 - Neuroplasticity/LTP Flashcards
How does a synapse get stronger? By increasing:
1) Probability of release – more Ca2+ flux into presynaptic terminal and more docked vesicles
2) Number of release sites – unsilencing of synapses (pre or postsynaptic)
3) Quantal size – increase AMPA receptors, change in AMPA receptor kinetics (increasing conductance
* it is unsure whether all AMPA receptors are saturated after vesicular NT release occurs, but if it is saturated, then putting more AMPA receptors increases EPSP response
Silent synapses
They have AMPA receptors sequestered in the postsynaptic dendritic spine that will only be inserted when called
TWO TYPES OF LTP
1) Non-associative: high freq stimulation of a single synapses is sufficient to strengthen that synapse
- a single synapse can bring upon LTP
2) Associative requires simultaneous firing of multiple synapses
- Based on the observation that LTP occurred only when presynaptic cell fired before post synaptic cell (e.g. EPSP then AP)
- it has to fire one millisecond or less (that’s why it seemed to appear to be simultaneous but its not)
- the closer to simultaneous firing then the higher the level of potentiation BUT it can never be simultaneous or LTP will not occur
When does LTP occur?
EPSP presynaptic then AP postsynaptic
Features of Associative LTP
1) Associativity/Cooperativity
For weak inputs (far away from cell body) to be potentiated, they must be paired with strong inputs
2) Specificity
Strong repetitive stimulation of one pathway can be sufficient to elicit LTP in one pathway but not in other unstimulated pathways
E.g. Only pathways that fire within one ms of the presynaptic EPSP will be affected
Is hippocampus part of neocortex?
No, neocortex is 6 layer thick and hippocampus is 3
Where is hippocampus found?
Medial temporal lobe and part of cerebral cortex
Function of hippocampus?
Spatial memory (RIGHT SIDE) and consolidation of ST to LT memory
What is the Hebbian Hypothesis?
Cells that fire together, wire together
Name the presence of 3 types of glutamate receptors at excitatory junctions
1) AMPA receptors causes Na+ entry and depolarization
2) NMDA receptors - nothing happens until Mg is expelled, in which case Ca2+ enters when glutamate binds
3) mGlu receptors activate PLC via G-proteins, leading to amplification by releasing Ca2+ from smooth ER
In non-associative LTP, the main source of Ca2+ is not through NMDA but through
VACC in the dendritic spine
Effects of NMDA stimulation
1) Ca entry via NMDA receptors
2) Ca release from intracellular stores
3) Ca entry via VACC
4) Activation of CaCam Kinase II
5) Activation of PKA and PKC (by Ca and DAG)
Where does CaCam Kinase II attach to in NMDA?
The tail
Role of CaCam Kinase II
- Phosphorylates AMPA receptors (increases conductance)
- Phosphorylate PSD-95 (receptor clustering protein) and cause greater clustering of AMPA receptors
- Necessary for structural synaptic plasticity - the formation of new active zones
Ca-activated enzymes in dendrites
Cam kinase II Nitric oxide synthase Phospholipase A2 (-> arachidonic acid) Calmodulin (-> Adenylate cyclase) Protein Kinase C Calpain (proteolytic properties)
