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Flashcards in lecture 21 Deck (11):

What is the role of the hippocampus?

- hippocampus - primitive part of cerebral cortex located medially in temporal lobe
– active during consolidation phase of explicit memory
- damage prevents formation of new long term explicit memories but does not disturb already formed memories
– does not prevent formation of implicit memories

- central to explicit memory
- contains within it maps of the environment, allowing the animal to locate itself within its environment, allowing memories to be put into context
- part of consolidation and tuning of memories


What is the role of the neocortex?

- explicit memory is associative
-- related information is recalled together (the husseins)
- recall of stored memory of an event activates parts of cortex activated when the event was sensed
-- the event is partially relived
- during long term memory formation (takes days) continual interaction between neocortex and hippocampus
- eventually the neocortex contains the memory and the hippocampus is not required


What is the structure of memory?

- stored as strength of connections between neurons in a network
-- 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

- over time, as these connections strengthen, a partial activation of this network now gives out at the far end the complete original stimulus
- this is an associated memory
- memory is a natural consequence of having interconnected neurons that are capable of strengthening or weakening their connections to each other


What is 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)
- Long term depression (LTD) is another form of Hebbian modification

- superposition catastrophe: one memory becomes too strong - there must be some mechanism for pruning over-strengthening of neuron synapses, neuronal homeostasis?


What are relavant physiological mechanisms to the development of memory?

- strengthening of synapses probably occurs via LTP
- weakening of synapses occurs via long term depression (LTD)
- for true long term effect need protein synthesis


What are LTP and LTD?

- fundamentally if you stimulate an axon and look at transmitter release from that axon, or the synaptic potential that it produces in its target cell, and you give two stimuli close together the size of the synaptic potential that you get on the second target cell will not be the same as the size you get on the first
- it will either be increased in a systematic way or depressed in a systematic way = facilitation and depression
- properties of the transmitter release properties and of the receptors at the appropriate site
- these mechanisms are temporary

- hippocampal pyramidal cell critical to memory formation
- apical dendrites get synaptic inputs from two different sets of axons (or whatever)
- axon set 1 are being stimulated at a low frequency to produce a particular series of action potentials, frequency too low for there to be stimulation from one cell to the next
- at a certain point a tetanus is induced in the set of axons in input one
- the size of the synaptic potential is dramatically increased after that tetanus
- neuron remembers that the particular input is very effective
- can last for a long time, up to a month

- can do the same thing but have the tetanus at a low frequency, not enough to stimulate the neuron
- size of the synaptic potential gets smaller
- lasts a long time
- neuron remembers that the particular input is ineffective

- in each of these cases there is an element of association becaues more than one axon is part of each input

- changes are more able to go back in hippocampus than in neocortex


What is a post-synaptic mechanism for LTP?

- glutamate excites AMPA receptors and unblocks NMDA receptors
- Ca2+ entering via NMDA receptors activates Ca2+ dependent kinases
- kinases phosphorylate AMPA receptors or cause insertion of AMPA receptors into terminal membrane
- Ca2+ can also enter via voltage gated Ca2+-channels


How do we have memory in a molecule?

Calcium-calmodulin dependent protein kinase II (CaMKII)
- found in spine cytoplasm
- associated in rings of 10 subunits
- Ca2+-calmodulin disinhibits kinase activity
- CaMKII is target for phosphorylation by CaMKII
- phosphorylation makes CaMKII constitutively active until dephosphorylated by a phosphatase
- memory stored in number of CaMKII molecules within ring that are phosphorylated


How is regulation of protein synthesis important to memory formation?

- phosphorylation, receptor sensitisation, increased receptor number – all time limited
- for long term memory need protein synthesis
- one mechanism identified in invertebrates involves phosphorylation of CREB (cyclic AMP response Element Binding protein), which regulates gene expression


Are NMDA receptors the only source of Ca2+?

- no
- back propagating dendritic action potentials can open voltage-dependent Ca channels
- Ca2+ entry via NMDA plus voltage-dependent channels greater than sum of separate routes of entry by themselves
- Can also increase cytoplasmic Ca2+ via release from intracellular stores
-- e.g. the metabotropic glutamate receptor mGluR1 causes Ca2+ release from endoplasmc reticulum
- timing of Ca2+ entry is key


What is spike timing plasticity?

- when action potential in post-synaptic neuron occurs before an EPSP total increase in Ca2+ ion is small
-- activates Ca2+-dependent phosphatase
- when NMDA-receptor mediated EPSP occurs before post-synaptic action potential increase in Ca2+ ions is much larger
-- activates CaM Kinase II
-- LTP