Cellular Mechanisms of Learning and Memory

Question 1

memory

Answer 1

• declarative or non-declarative
• declarative are available to consciousness-daily episodes, words and their meanings, history
• non-declarative are motor skills, associations, priming cues, puzzle solving skills

Question 2

clinical cases

Answer 2

• HM- had epilepsy, removed hippocampus and temporal lobe, couldn’t make anterograde memories anymore
• normal IQ, short term, memory from before operation
• could perform non-declarative procedural tasks and get better at them-tracing the star
• RB-anoxia from cardiac arrest- similar but more modest memory impairment- CA1 of hippocampus

Question 3

spatial learning in rats

Answer 3

• depends on hippocampus

- finding hidden platform in water after 10 trials improved in mouse with hippocampus

Question 4

brain areas associated with declarative memory disorders

Answer 4

• basal forebrain
• fornix
• thalamus
• prefrontal cortex
• mammillary body
• amygdala
• Rhinal cortex
• hippocampus

Question 5

hippocampus and declarative storage

Answer 5

• association cortex
• widespread projections from association neocortex converge on the hippocampal region
• output of hippocampus is ultimately directed back to these same neocortical areas

Question 6

acquisition and storage of declarative

Answer 6

• short term in hippocampus and related structure

- long term in cortical sites- wernickes area, temporal cortex

Question 7

acquisition and storage of nondeclarative

Answer 7

• short term unknown but probably widespread

- long term-cerebellum, basal ganglia, pre-motor cortex, other sites related to motor behavior

Question 8

immediate

Answer 8

-fractions of seconds

Question 9

working memory

Answer 9

seconds-minutes

-ability to hold and manipulate information in mind for seconds to minutes while it is used to achieve a particular goal

Question 10

long term

Answer 10

days-years

-ENGRAM-physical embodiment-depends on long term changes in the efficacy of synaptic transmission

Question 11

intrinsic trisynaptic circuitry

Answer 11

• studying basis of synaptic modifications
• synaptic strengthening is what makes memory storage
• entorhinal cortex, granule cells, (mossy fibers), CA3 and CA1 pyramidal cells, through Shaffer collaterals
• LTP happens throughout

Question 12

LTP

Answer 12

• long term potentiation
• provides a plausible neural mechanism underlying enduring changes in a part of the brain known to be important for declarative memories
• initially discovered from rabbits with hippocampal electrodes, used slices to find out more

Question 13

LTP 2

Answer 13

• long lasting increase in synaptic strength
• observed in synapses throughout the brain
• commonly examined at shaffer collateral CA1 synapses
• pyramidal CA3 neurons in hippocampus send axons to synapse on CA1
• intense high F stimulus is given through the stimulating electrode to activate a group of postsynaptic CA1 neurons
• control is set of collaterals with weak low F stimulus

Question 14

LTP protocol

Answer 14

1. baseline recording est by providing a low F and low intensity stimulus- only AMPA
2. pathway 1 receives a brief high F and high intensity stimulus (activates NMDA for that 1 sec). pathway 2 receives only low F/low intensity
3. LTP is observed only in pathway 1-strengthening EPSP after returning to low F stim
   - LTP blocked using NMDA receptor antagonist- need NMDA for LTP (only for a second even)
   - persists for hours in vitro and days/weeks in vivo
   - dendritic spines change shape or appear in LTP

Question 15

properties of LTP

Answer 15

• specificity- only pathway 1 if only one stimulated

- association-depolarization can travel and strengthen an associated synapse

Question 16

NMDA

Answer 16

• coincidence detector-needs glutamate + glycine
• can only open when the depolarization is sufficient- high f and intensity
• need to release Mg block
• also allows Ca in-responsible for LTP

Question 17

signal underlying LTP

Answer 17

• Ca dependent insertion of AMPA receptors in post-synaptic membrane-increases protein kinases-which cause enhanced release of glutamate and increased AMPA receptors
• expression and maintenance of LTP involves increased AMPA receptors
• LTP might involve increase in glutamate release from presynaptic terminal
• metabotropic glutamate receptor activation contributes because it promotes release of Ca stores via IP3 and increases PKC-enhances NMDA

Question 18

protein synthesis

Answer 18

• need it to maintain LTP

- no synthesis causes LTP to decay within a few hours

Question 19

changes in synaptic transmission

Answer 19

• long term LIP requires gene transcription and protein translation
• kinases diffuse to CA1 cell nuclei and influence genes that trigger long lasting post-synaptic modifications
• in presynaptic terminals, kinases diffuse to CA3 nuclei and cause presynaptic structural changes
• LTP causes and increased number of synapses on dendritic shafts and increases in stubby spine synapses
• increase in number of presynaptic terminals from axon terminal sprouting

Question 20

LTD

Answer 20

• long term depression
• long lasting decrease in synaptic strength that provides an attractive neural mechanism for certain forms of learning and memory
• observed at shaffer collateral CA1 synapses when they are stimulated at a low rate for long periods of time
• EPSP is depressed for several hours
• specificity and NMDAR-dependence, but Ca signal is different
• small and slow rises in Ca lead to activation of phosphatases, not kinases
• LTD associated with internalization of AMPA receptors, not insertion of them
• LTD can erase LTP and vice versa- common synaptic site of action