Memory

Question 1

Define learning, memory and engram

Answer 1

1. Learning - Acquisition of new information or knowledge
2. Memory - Storage or retention of acquired knowledge
3. Engram - physical representation or location of memory

Question 2

What are the 3 classifications of memory

Answer 2

1. Declarative- what something means, historical events, things that have happened to you
2. Emotional- preferences, aversions, like certain things
3. Procedural- motor skills, talking, walking etc, associations- linked to emotional, associate differentiate stimuli, problem solving

Question 3

Which areas of the brain are involved in the brain

Answer 3

1. Actually the hippocampus is pretty much involved in all of them – something of a relay station for all types of memory, but is particularly key to the declarative type of memory
2. Amygdala- emotional
3. Hippocampus- declarative
4. Cerebellum- motor procedural
5. Striatum- priming cues and associative

Question 4

How do we know which areas of the brain are important

Answer 4

1. Henry Molaison (‘HM’) had temporal lobes removed for epilepsy. Overall – short-term memory severely affected, long-term memory generally OK
2. Suffered from severe anterograde amnesia: although his working memory and procedural memory were intact, he could not commit new events to his explicit memory.
3. However, his ability to form long-term procedural memories was intact; thus he could, for example, learn new motor skills, despite not being able to remember learning them.
4. Severe anterograde amnesia (limited retrograde amnesia)
5. Working memory intact – could not form new long-term memories

Question 5

What is the engram- Hebb’s law

Answer 5

1. Donald Hebb (1949) - when two neurones are active, so that one repeatedly releases neurotransmitter at the same time as its postsynaptic partner is firing action potentials, then that synapse will become stronger.
2. “cells that fire together, wire together”
3. Synapses strengthened by intense activity
4. memory depends on populations of interacting neurones
5. pattern of strengthened synapses defines memory

Question 6

Describe how a memory is formed

Answer 6

1. All neurons are connected to each other
2. External stimulus presented- e.g. visual stimulus for visual cortex
3. Activates neuronal assembly
4. All activated at same time
5. Produce reverberative activity- short term memory
6. Need to convert to long-term memory
7. Strengthened synapse- connections between neurons are synapses and are strengthened – engram
8. Engram- collection of neurons that has now encoded a specific memory
9. Memories can be retrieved from engram- only a subset of neurons have to be activated to trigger memory- so triggers activation of whole engram
10. Brain fills in the gap

Question 7

How do we study synaptic strengthening

Answer 7

1. electrophysiological experiments
2. Stimulate glutamatergic afferent which releases glutamate on to postsynaptic neurone and record membrane potential of neuron
3. Increase in the strength after repeated stimulation is called Long Term Potentiation (LTP)
4. LTP happens after brief repetitive activation

Question 8

What is required to induce LTP

Answer 8

1. LTP induction has a voltage threshold
2. Simulate glutamatergic presynaptic neuron and record postsynaptic activity
3. Critical requirement of Ca to induce LTP

Question 9

How are NMDA receptors involved in LTP

Answer 9

1. Glutamate alone - no current flows
2. Channel blocked by Mg++
3. Depolarisation to repetitive activation of AMPAr relieves Mg2+ block
4. Both Ca and Na flow through NMDAr channel
5. Ca-entry - cellular changes lead to increased AMPAr response – LTP

Question 10

How is LTP manifested

Answer 10

1. Normally glutamatergic
2. Postsynaptic
   a) More AMPAr- synthesise more
   b) More sensitive AMPAr- phosphorylation
   c) More synapses- making more synapses
3. Presynaptic
   a) Increased release- more neurotransmitter released
   b) More release sites
   c) More vesicles

Question 11

Describe LTP induction mechanisms

Answer 11

1. Phosphorylation of AMPAr by PKC- activated by calcium influx
2. Insertion of new receptors by CaMKII.- cause shuttling of intracellular AMPA receptors to cell surface so glutamate can bind and cause greater stimulation
3. Also synthesis of new receptors
4. Retrograde messenger - nitric oxide - presynaptic changes
5. Synthesized postsynaptically and diffuses across to nerve terminal to cause presynaptic changes

Question 12

What receptors underlie memory formation and describe experiment to show this

Answer 12

1. NMDAr underlie memory formation
2. Morris water maze
3. Put rat in tank of water
4. Rat can’t see hidden platform under water
5. Comes across platform which it stands on
6. After learning- takes shorter path
7. If learning in presence of NMDAr antagonist they don’t remember where the platform is

Question 13

Give summary of formation of LTP memory

Answer 13

1. One form of LTP (memory) depends on NMDAr
2. induced by NMDAr activation
3. expressed by AMPA receptors
4. maintained by changes in number/sensitivity of postsynaptic AMPAr and structural changes
5. also maintained by presynaptic alterations of glutamate release
6. Very simplistic. LTP/memory formation strongly influenced by many factors
7. e.g. modulated by diffuse amine and cholinergic systems

Question 14

Describe Pavlovian (classical) conditioning

Answer 14

1. Food= salivation
2. Bell= no salivation
3. During conditioning
4. Food + Bell= salivation
5. Dog learned to associate bell with food
6. So just sound of bell = salivation
7. PTSD- unpleasant event can be triggered by various stimuli
8. Drug addiction- people who take drugs do with same people, same time of day, same environment- priming cues

Question 15

What do fMRI scans show about drug addicts

Answer 15

1. Look at part of brain activated
2. Cocaine addicts
3. Got them to watch neutral video and then priming cue for cocaine addict
4. Makes the want to take cocaine
5. Brain activated by priming cue