Lecture 21- Molecular mechanisms of memory Flashcards Preview

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Flashcards in Lecture 21- Molecular mechanisms of memory Deck (43)

Where is the hippocampus?

-primitive part of cerebral cortex located medially in temporal lobe


When is the hippocampus active?

during consolidation phase of explicit memory


What does the failure of consolidation result in?

-no formation of long term memory -appears in alzheimer's


What happens when the hippocampus is damaged?

- prevents formation of new long term explicit memories but does not disturb already formed memories -Does not prevent formation of implicit memories (but can't remember how you formed them)


What role does hippocampus play in explicit memory?

-central to explicit memory= cannot form it without it -the transmission from working memory to explicit long term memory -becomes active again during the consolidation process (when you're asleep) -part of tuning of memories, need to be able to weight the balance of memories, what happened today, yesterday etc.


What does it mean that memory is associative?

-have a memory but also lot of facts surrounding it, = pulling one element then brings things associated with it.


What is a characteristic of explicit memory?

-it is associative -related information is recalled together


What happens when you're recalling a memory?

-Recall of stored memory of an event activates parts of cortex activated when the event was sensed – The event is partially relived


What is the role of the neocortex in memory?



What happens during long term memory formation?

-During long term memory formation (takes days) continual interaction between neocortex and hippocampus -after a while you don't need the hippocampus to recall the memory,


How is memory stored?

-as strength of connections between neurons in a network


Is memory dependent on individual neurons?

-Individual neurons can participate in several memories -Distributed, rather than depending on single neurons -Usually located close to the region that responds to a specific modality


What is sparse coding?

-one neuron per memory not true, more neurons involved in one memory, can multiply the numbers of memories you can have


What is the structure of memory?

-this is not only for neurons -collection of neuron-like interconnected elements -when give a stimulus then all will be activated (the ones that are sensitive to it) -interactions between the neurons get stronger and stronger -consequence is when stop the training stimulus= but not they are strongly interconnected and activating one will activate the others -partial activation gives the complete original stimulus =associative memory -memory is a natural consequences of having neurons taht can change the connections between them in response to repeated stimuli


What is long term potentiation? (Hebbian modification)

Long term activity dependent plasticity that satisfies the criterion that synapses strengthen when pre- and post-synaptic neurons are active at the same time -Long term potentiation (LTP) -one neuron active at the same time as postsynaptic nerons= that strengthens the connection LTP -with repetition becomes a memory trace


What is long term depression?

-(LTP) is another form of Hebbian modification -where presynaptic and postsynaptic neuron are not active at the same time= then less connection! LTD


What is neuronal scaling?

LTP= even though synapse gets stringer, adjustment (neuornal homeostasis) to frequencies, so when the connection stronger the firing stronger but not that much neuronal scaling= brings the synapses to appropriate level, so the connection not too strong


How is LTD self-regulated?

-LTD= is self regulating, eventually will stop working if too strong (as no connection)


What does the strengthening of synapses occur via?

-via long term potentiation (LTP)


What does the weakening of synapses occur via?

-occurs via long term depression (LTD)


What do we need for true long term effect (memory)?

-protein synthesis -you need to alter the synapse permanently to get a long term memory -if block protein synthesis then no memories formed -point of LTP and LTD is to set up the system to have the long term changes in synapse (protein synthesis)


What does this picture show?

-LTP -frequency is the test -tetanus= high frequency stimulation is applied to the axon 1, the size of the output is increased after this -the effect lasts for up to a month =if put the same input to input 2 then not increased -the neuron remembers that only input 1 was stimulated


What does this picture show?

-LTD -give stimulus that is not strong enough to activate the neuron -then the response gets smaller, this effect lasts long = LTD -remembers that this input is ineffective -the other set of inputs doesn't get activated -associated already


Why is it easier to form new memories in the hippocampus?

in hippocampus= the changes not as constant in absence of stimulation, so can form new memories more easily in neocortex (the LTD and LTP)


How long does facilitation and depression last?

-temporary things (millisecond in facilitation, seconds in depression)


What is the postsynaptic mechanism for LTP?

1.-glutamate excited AMPA receptors (Na+ going in) 2.-the depolarisation unblocks NMDA receptors 3.-Ca2+ going in through the NMDA 4.-Ca2+ activates dependent kinases 5.-the kinases phosphorylate AMPA receptors or cause insertion of AMPA receptors into the terminal membrane -thus the cell is more easily excited by glutamate now -more activation -happens on the postsynaptic terminal on synaptic spines


How are NMDA receptors blocked?

-by a Mg+ ion, it is unblocked by the excitation of AMPA receptors and the influx of Na+ ions


Where is the Ca2+ during the LTP mechanism?

-in the dendritic spine not in the dendrite


How can Ca2+ enter the cell in LTP mechanism?

-via NMDA receptors -also voltage gated Ca2+ channels


Where is calcium-calmodulin dependent protein kinase II (CaMKII) found?

-in spine cytoplasm (of neurons) -associated in rings of 10 subunits -chemical memory!


What disinhibits the CaMKII activity?

Ca2+ - calmodulin complex -activated when Ca2+ influx when NMDA receptors activated in LTP


What happens to CaMKII when Ca2+ influx?

1.-normally the hinge like subunit of CaMKII is off 2. the hinge opens upon binding of Ca2+- bound calmodulin, freeing the catalytic region to add phosphate groups to other proteins 3.large elevation of Ca2+ can cause phosphorylation of one subunit by another (autophosphprylation) which enables the catalytic region to stay on permanently


Where is calmodulin found and what can it do?

-found in the cytoplasm, when bound to calcium can modify fucntions of other things in cell


What does phosphorylation of CaMKII do?

-Phosphorylation makes CaMKII constituitively active until dephosphorylated by a phosphatase


How is memory stored in CaMKII?

-Memory stored in number of CaMKII molecules within ring that are phosphorylated


What is one of the mechanism of protein synthesis in formation of long term memory?

-involves phosphorylation of CREB which regulates gene expression


What is CREB?

-(cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes


What opens the Ca2+ voltage gated channels? (in LTP)

-Back-propagating dendritic action potentials can open voltage-dependent Ca channels


How can you also increase the cytoplasmic Ca2+ ?

-Can also increase cytoplasmic Ca2+ via release from intracellular stores – e.g. the metabotropic glutamate receptor mGluR1 causes Ca2+ release from endoplasmic reticulum


What is the sum of Ca2+ entry via NMDA and voltage-dependent channels?

Ca2+ entry via NMDA plus voltage-dependent channels greater than sum of separate routes of entry by themselves


Why is the timing of Ca2+ entry key?

-Ca2+ is needed for both LTD and LTP= which one it is, is dependent on the amount


When do we have an LTD? (spike timing plasticity)

When action potential in post-synaptic neuron occurs before an EPSP total increase in Ca2+i is small – Activates Ca2+-dependent phophatase – LTD


When do we have LTP? (spike timing plasticity)

When NMDA-receptor -mediated EPSP occurs before post-synaptic action potential increase in Ca2+i is much larger – Activates CaM Kinase II – LTP