Synaptic Plasticity Flashcards
What is Hebbian Plasticity?
Theoretical idea that when neurons are active together, that strengthens the wiring between them. Simultaneous pre and post synaptic connectivity.
Represents idea that various components of a memory are stored in different neurons and they are connected in a circuit.
Why are neurons active at the same time?
Reacting to aspects of the same stimulus.
What happens when you are presented with multiple previously unconnected stimuli? Then with just one of them.
Neurons tied to the individual stimuli are excited, and you see reciprocal connections (common in CA3)
Connections get stronger when neurons fire at the same time. Stimulus is removed, neurons go back to resting activity levels.
Later after learning, if you present with just 1, all the other neurons will fire in response to 1 stimulus being presented due to strengthened connections.
- 1st, just neuron associated with stim is activated, then recurrent collateral axons are recruited and linked axons are activated.
this may happen (connections formed) prior to the learning experience for random reason - but not strong enough to form a circuit until memory formation occurs
Describe long term potentiation as a synaptic model of memory? How was it first studied?
First studied in dentate gyrus of rabbits.
Potentiation meaning making something stronger.
- Stimulate axons with electrode, post synaptic responses recorded, over HOURS they keep stimulating in routine bursts. Then you give a really high frequency stimulation, and from then on even the weak stim will give higher EPSP. This suggests long term storage.
Know its getting stronger because different pathway was stimulated once/minute which caused no increase in EPSP.
Can remain potentiated for days.
Why does LTP at hippocampal synapses depend on the NMDA receptor?
NMDAR is blocked by MG2+ at times of low activity - not super important for regular synaptic transmission.
But in times of higher depolarization, mg is pushed out of the way, allowing calcium to enter the cell which causes increase in synapse strength.
NMDAR acts as a coicidence detector for neurons that fire and wire together.
How does Calcium signalling change the synapse?
- Retrograde singalling (travels back to presynaptic cell and induce more NT release
- Phosphorylation of AMPA receptor to make it more efficent and increase rate of Na+ flow into the postsynaptic cell
- Inserting new Ampa receptors into Postsynaptic cell membrane - NT has more binding locations.
What are the fundamental properties of LTP? How to choose what gets remembered.
- Normal conditions: no LTP because Mg2+ block is in place, circuits are activated and transmission of signal is enough to percieve things but not encode them into memory. (you don’t remember everything in the long term)
- Cooperativity
- or convergence. Enough spatiotemporal summation to knock off Mg2+ block, and induce LTP. Multiple WEAK synapses are active enough to cause encoding. Basically a threshold is met spatially. - Associativity: strong input in one synapse relieves mg2+ block and enables LTp in a different weaker synapse. Different stimuli are activating strong synapse and the weak one. These stimuli become LINKED and the weak one can activate the entire circuit.
This is firing together and wiring together. Weak and strong synapses don’t have to be nearby on the neuron. - Specificity: LTP only occurs at active synapses (must be at LEAST weakly activated, not at inactive ones to prevent storage of irrelevant info)
What are the two types of LTP?
Early: decays within hours. Does not require protein synthesis.
Late: requires more stimuli but persists longer.
Distinguished by protein synthesis. If you add anisomycin (protein synth blocker) it decays much faster back to baseline.
What are some mechanisms involved in late LTP?
- cAMP leads to CREB dependant transcription which upregulates PRPs. Signalling to nucleus depends on cAMP.
CREB transcription factors induce expression of genes to help them get stronger. THey express PRPs - PRPs are necessary for long term strutural synapse strengthening and new synapse formation. enable formation of new synapses, can strengthen cells that went through early phase ltp
- epigenetic modifications to the genome are also required for some types of LTP and memory.
- change the way the genome is accessed. Genes are more/less active in different cells depending on various chemicals.
LTP works by
i. Releasing more NT
ii. hyperphosphorylation of receptors making them more efficent.
iii. proteins synthesized and genes expressed (longer term)
How do the PRPs know where to go?
Synaptic tagging and capture. to strengthen the ‘right’ synapses.
Both strong and weak stimuli have tags activated. but only strong stimuli induce PRPs to be expressed.
The strong stim causes cAMP to go to nucleus and induce synthysis of PRPs which diffuse through the cell. The PRPs target the tags on synapses and enable late LTP.
- weak stim ‘hijacks’ strong stim by converting early ltp to late ltp when a strong stimulus is around since the PRPs are diffuse in the cell.
Weak stims without any strong ones around are not strong enough to cause gene transcripton, so no PRPs, so the early LTP decays to baseline and no memory (long term) is formed.
think: justin beiber (late ltp) and granola (early ltp TURNED late by strong stim present)
What are the two types of associativity and their time scales?
NMDAr dependant (miliseconds) - weakly stimulated synape exploits depolarization of a strong synapse (hijacks it) to enable association between stimuli that occur close together
PRP dependant: weakly stimluated synapse exploits PRP synthesis, and keeps its ‘weak’ tag out for hours, which can then be stimulated by a PRP later. i.e. remembering things before a traumatic event. helpful in retracing steps and evolutionary processes.
What is pattern separation? Pattern completion?
The dentate gyrus performs pattern separation. This allows for divergence of information and separation of memories.
lateral inhibition reduces activity of other neurons to sharpen the contrast of representation in CA3 pyramidal neurons. Using feed forward inhibition (activate and inhibit some ca3 neurons)**
Different experiences activate a different subset of neurons in the dentate gyrus. the DG has a large number of neurons in comparison to entorhinal cortexes. Allows for divergence of incoming info.
- some overlap, some are different. This amplifies the differenges int hem.
CA3 does pattern completion. Reccurent axons connect ca3 neurons to themselves to link components of a memory, LTP binds them. reccurent collateral axons. This allows you to get a cue from a memory and then be able to recall the whole thing cause they’re interconnected as heck.
This can also be done using firing rates rather than specific neurons.
Describe cochlear implants
an implant that exploits the tonotopic map in order to stimulate the auditory system and communicate sound info. Passes current to cochlea at different points based on a microphone. Since frequency distribution is known, makes it easier to take auditory info and stimulate.
Electrodes depolarize membrane as opposed to cilium.
How do we exploit genetics to manipulate memory?
Promotors used to drive cells specific expression of protiens. LIke GFP except to modify function.
Since you can’t stimulate everywhere with electrodes, you need some other way. a common way to do this is OPTOGENETICS
What are optogenetics?
Using light sensitive proteins to activate and inhibit specific neurons. In order to shut down specific cells in a memory this is commonly used.
The hardware requires surgery to implant the optical fiber, where you shine the light, directly under is stimulated.
Channelrhodopsin: codes for a light sensitive channel, passes sodium to depolarize the membrane, and by using the right promotor you can get this gene wherever you want. Sensitive to 470nm blue light. When you shine it, you get an AP
Halorhodopsin: responds to orange wavelength light, is a PUMP that pumps chloride and inhibits activity. Orange light shone = memory potential becomes hyperpolarized.
