Synaptic plasticity - learning and memory COPY Flashcards
TYPES OF MEMORY AND LEARNING
i) which type of memory is concious and which is unconcious?
ii) what memories are explicit memories? (2)
iii) which type of memory are procedural and classical conditioning?
iv) what is learning? what does it involve changes in? what does this alter?
i) concious = explicit and unconcious = implicit
ii) explicit = facts and events
iii) procedural and classical conditioning = implicit memory
iv) learning is the response of the brain to enviro events and involves adaptive changes in synaptic connectivity which alter behaviour
WIRING AND SYNAPTIC CONNECTIONS
i) which cortical layer does the thalamus input to?
ii) what is the engram?
iii) draw Hebbs model for cell assembly
i) layer 4
ii) engram is the change in the brain accounting for a memory trace
HEBBS MODEL OF ASSEMBLY
i) what is needed for the activation of the cell assembly? what happens to this activity after the stimulus is removed?
ii) what type of modifications strengthen the reciprocal connects between neurons that are active at the same time?
iii) what do the strengthened connections contain?
iv) what happens if the activation persists for a long time? what effect does this have on reciprocal connections?
v) what happens if part of the stimulus re-appears in the environment?
i) an external stimulus - the activity persists after the stimulus is removed
ii) hebbian modifications strengthen reciprocal connections
iii) strengthened conncetions contain the engram for the stimulus
iv) if activation persists then there is a consolidation process that makes reciprocal connections even more effective
v) if part of stimulus reappears in the environment then the whole cell assembly can be activated due to learning already taking place
RULES OF SYNAPTIC MODIFICATION
i) what happens to neurons that fire together?
ii) what happens to neurons that fire out of sync? when may this be important
iii) what does strengthening and weakening of synaptic connections provide a means for? (2)
iv) would three individual sensory inputs (visual 2x olfactory) be sufficient to create a EPSP to fire an action potential? what happens if two of the inputs fire together?
i) they wire together - strengthen synapses and form new neurons
ii) they lose their link - it can be important to weaken some connections so you dont end up with noise
iii) strength and weakening synapses provides a means for learning and memory formation
iv) individual inputs may not result in an EPSP and AP but two inputs firing together can and will associate the two (eg smell and sight of a rose) as those synaptic connections are strengthened
LONG TERM POTENTIATION
i) what mechanism does it underlie?
ii) which brain area can this process easily be recorded from? which specific cells? why is it recorded from here?
iii) which synapses are subjected to high frequency stimulation? what is this also known as?
iv) which pathway are the stimulated synapses found in? which area is then recorded from with an electrode? what is seen in relation to EPSP size several minutes after high freq stimulation?
v) what can a single train of high frequency pulses lead to? how long does this last? how can this be strengthed to last for longer?
i) LTP underlies synaptic strengthening
ii) easily recorded from the hippocampus (cells in the dentate gyrus) as shape and size of HC allows easy access
iii) excitatory hippocampal synapses subjected to high freq stimulation aka tetany
iv) stimulate synapses in the perforant pathway and record from the dentate gyrus
- increase in EPSP size several minutes after a high frequency stimulation is applied
v) single train of high freq pulses can lead to LTP that lasts a few hours
- multiple high frequency stimulation can strengthen the LTP and allow it to last for days/months
TYPES OF LTP
i) what is temporal LTP? how may this be achieved?
ii) what is associative LTP? how may this be achieved?
iii) what is specific LTP? how can this be demonstrated?
i) summation of inputs that reach a stimulus threshold that leads to induction of LTP
- can be achieved by repetitive stimulation (high freq) eg tetany
ii) simultaneous stimulation of a strong and weak pathway will induce LTP in both pathways
- cells that fire together wire together
iii) LTP at one synapse is not propagated to adjacent synapses eg it is input specific
- sight and smell of rose are associated but sight of rose and smell of onion are not - so seeing a rose does not make you smell an onion
LTP AT SYNAPTIC LEVEL
i) when Glu is released onto an inactive cell - which receptor is activated after the first few stimulations? which receptor remains inactivated? why?
ii) when Glu is released onto an active cell - what happens? which two channels are activated? which ions flux through each?
i) Glu > inactive cell > activates AMPA to create an EPSP
- NMDA remains inactivated as the depol from AMPA activation isnt enough to expel the Mg2+
ii) Glu release onto an active cell > depol
- AMPA is activated = fluxes Na+
- Mg2+ block from NMDA is relieved = fluxes Ca2+
SECOND MESSENGER SYSTEMS AND LTP
i) name two things that Ca2+ entry through an NMDA receptor leads to activation of?
ii) what two actions does calcium entry have on AMPA? what effect does this have on EPSPs?
iii) in relation to AMPA receptors - what happens before the strong depolarising pulses are paired with EPSPs?
iv) what happens after this?
i) calcium entry to NMDA activates calcium calmodulin dependent protein kinase II (CamKII) and PKC
ii) calcium entry causes phosphorylation of existing AMPA receptors (increasing effectiveness) by PKC
- stimulates insertion of new AMPA into the membrane
iii) before strong depol = few AMPA Rs and small EPSPs
iv) after strong depol = more AMPA in mem working more effectively, larger EPSPs and LTP
CaMKII - MOLECULAR SWITCH
i) what is it and what does it ultimately allow?
ii) what is it activated by?
iii) what type of catalytic activity does it have?
iv) what type of activity does it have once it is phosphorylated? does it require sustained calcium?
v) what effect does maintained phosphorylation have on AMPA? what does this allow?
i) a molecular switch that maintains increased excitability of neuron for mins to hours (sustained activity after repolarisation)
ii) activation by calcium entry through NMDA receptors
iii) has auto catalytic activity - can phos itself
iv) once phos it is constitutively active and no longer needs calcium
v) maint phos allows insertion of AMPA receptors inot the membrane after the depol stim has receeded
- allows stimulation of post synaptic cell to the original stimulus
PRESYNAPTIC EVENTS IN LTP - EARLY PHASE
i) how does a post synaptic neuron feed back to a presynaptic neuron? what transmitter is used?
ii) what activates this transmitter?
iii) what does the transmitter activate in the presynaptic terminal?
iv) which transmitter ultimately has inceased release from the synaptic bouton?
v) what phase of LTP does this happen in?
i) post syn feeds back to pre syn by retrograde transmission using NO
ii) calcium moving through NMDA channel actives NOS > NO
iii) NO diffuses from post syn to pre syn and activates guanylyl cyclase > cGMP
iv) increase in glutamate release
v) early phase LTP (mins to hours)
LATE PHASE LTP
i) what is required for long lasting LTP? how long does it last for?
ii) what inhibits the consolidation of long term memories and LTP? what does this confirm?
iii) what two stages come after acquisition (training) in memory formation?
iv) injection of what post acquisition can inhibit recall? what does this demonstrate about what is required for consolidation?
v) which protein promotes gene transcription? what does it replace on DNA?
i) protein synthesis - lasts for days/months
ii) protein synthesis inhibitors can inhibit long term memory formation and LTP
- confirms that protein synthesis is required
iii) acquisition > consolidation > recall
iv) injection of prot syn inhibitor post acquisition can inhibit recall - shows that it is necessary for consolidation
v) CREB1 promotes gene transcription
- PKA and CaMKII replace CREBII with CREBI
EARLY VS LATE PHASE LTP
i) how long does early phase LTP last? movement of which ion through which receptor mediates it?
ii) what happens to AMPA receptor efficiency in early phase LTP?
iii) how long does late phase LTP last? what does it require? name the type of change it involves
iv) what is the first thing that happens in a calcium activated signal transduction cascade? what three things eventually then happen when it filters back to the cell body?
v) what type of synapse is generated after LTP has occured? how does this affect the contact between the two cells
i) mins to hours
- calcium moving through NMDA receptors mediates it
ii) enhanced AMPA receptor efficiency
iii) late phase lasts hours, days, months
- requires protein synthesis
- involves morphological change (estab of new synapses)
iv) calcium activation > activates new protein synth from dentritically localised mRNAs
- then filters back to cell bod to stimulate CREB mediated gene expression, prot syn and recruit of new proteins to synapse
v) after LTP = perforated synapse = increased contact between two cells
LONG TERM DEPRESSION
i) what type of stimulation creates LTP? what type of stimulation creates LTD?
ii) what is LTD?
iii) what happens to AMPA receptors? (2)
iv) what levels of calcium are seen? what does this cause activation of?
v) what do LTP and LTD reflect bidirectional regulation of? (2)
i) high frequency stim = LTP
- low frequency stim = LTD
ii) LTD weakens synapses to make constructive use of those strengthened by LTP
iii) AMPA receptors are dephosphorylated and removed from the membrane
iv) low level rises in calcium are seen and this activates phosphatases rather than kinases
v) phosphorylation and number of post synaptic AMPA receptors
LTP AND LTD
i) label diagram A-D
A = high freq stimulation B = LTP
C = low freq stimulation D = LTD
CHANGES IN SYNAPTIC ACTIVITY AND LEARNING
i) which receptor activity in the hippocampus is essential for both LTP and LTD
ii) name an antagonist to this receptor that blocks hippocampal LTP? what experiment does this block learning in?
iii) what does high freq stimulation produce in human inferotemporal cortex from HC maint in vitro produce? what does low freq stim produce? what does this show?
i) NMDA activity in the the hippocampus is essential for LTP and LTD
ii) AP5 is an NMDA receptor antagonist that blocks LTP
- can block learning in the morris water maze (rat doesnt swim to platform - blocks learning)
iii) HFS produces LTP and LFS produces LTD
- shows whats seen in rodents is also seen in humans
