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)
Retrograde messengers - able to rapidly diffuse across membranes
Arachidonic acid Nitric oxide Carbon monoxide O2- (superoxide) Cannabinoids
Mossy Fibre Synapse Teacher Hypothesis
1) One MF is activated resulting in CA3 pyramidal neuron firing
2) A back propagating AP travels the length of the dendrite
3) Activated A/C pathways temporally linked to the CA3 AP are potentiated
Dendrites are not always passive, some can propagate signals like axons, but slower. The MF synapse causes an AP which back-propagates up the dendritic tree.
Dendrites are not always passive, some can propagate signals like axons, but slower. The MF synapse causes an AP which back-propagates up the dendritic tree.
Two phases of LTP
Early (electrical-chemical) - changes regarding transient increase in calcium, phosphorylation, VACC etc.
Late (structural) - increase in N (number of release sites), transcriptional changes involving CREB
Effects of NMDA Stimulation
- Change in probability of vesicle release (This is the earliest phase of LTP)
- Change in size of current produced by each AMPA receptor
- Change in number of AMPA receptors
- Change in the electrical excitability of the dendritic membrane
- Production of a new dendritic spine
BDNF
Important in structural phase, if you activate NMDA long enough, you will get BDNF. During physical and mental exercise, BDNF is released.
HOW SIGNIFICANT ARE NMDA RECEPTORS?
- NMDA receptors are required for associative LTP
- Some synapses with NMDA receptors do not show LTP (eg motor neurons)
- The majority of CNS synapses have NMDA receptors - but it is not certain that they all show LTP
- Do NMDA Receptors have other functions? Probably.
Is LTP is reversible
Yes potentiation will eventually be lost if the synapse is not stimulated
Rhythms of the Brain are observed using
Theta 5 - 10 Hz - it disappears when you fall asleep
What is theta rhythm dependent on?
ACh
In rodents 60% of CA3 pyramidal neurons are
Place cells
Where are place cells found?
Medial part of entorhinal cortex, CA3 Pyramidal neurons
When do place cells fire?
When you cross a specific location in 2-D space
Where is spatial information coming from - where are the place cells getting info from?
Comes from Grid cells (found in entorhinal cortex - but not all cells here are grid cells)
When theta rhythm is at its most negative it is easier or harder for neurons to fire?
Harder - no cells are going to have AP
Phase precision?
The spiking of a place cell earlier in the phase cycle relative to the theta rhythm of the hippocampus as you move closer to the centre of a space.
Where are head direction cells found?
Post-subiculum, retrosplenial cortex, thethalamus (the anterior and the lateral dorsal thalamic nuclei), lateral mammillary nucleus, dorsal tegmental nucleus, striatum and entorhinal cortex
