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PH3501- Neuropharmacology > Lec 11- Learning and memory > Flashcards

Lec 11- Learning and memory Flashcards

1
Q

definition of learning and memory

A
  • Learning- acquisition of new information or knowledge
  • Memory- the retention of learned information
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2
Q

Human memory- Declarative

A
  • Daily episodes
  • Words and meanings
  • History
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3
Q

Human memory => Procedural

A
  • Motor skills
  • Associations
  • Priming cues
  • Puzzle solving
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4
Q

The temporal lobes and declarative memory

A
  • Electrical stimulation => Temporal lobes => Hallucinations recollection of past experience
  • Ablation => Temporal lobes => Retrograde or anterograde amnesia impairment of long term memory
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5
Q

HM and Temporal Lobectomy

A
  • Anticonvulsant resistant seizures
  • Bilateral removal of medial temporal lobe was successful in alleviating seizures
  • No effect on personality, intelligence or perception
  • Extreme anterograde amnesia- lacks the ability to form new declarative memories
  • Procedural short term and long term memory was normal
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6
Q

Henry Gustav Molaison

A
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7
Q

Normal v H.M.

A
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8
Q

Hebb and memory storage

A
  • Activity will occur (external stimulus) and activate a certain amount of cells within the hippocampus
  • Paramydal cells will fire in a certain pattern
  • The more times this stimulus occurs then more cells will fire
  • After time even if we get a part of a stimulus we can still identify the stimulus as a whole
    *
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9
Q

Hebbs law

A
  • Donald Hebb (1949) a Canadian scientist, said that when 2 neurones are active
  • so that one repeatedly releases neurotransmitter at the same time as its post-synaptic partner is firing APs
  • Then that synapse will become stronger
  • This is call Associativity
  • It is sometimes said that ‘cells that fire together wire together’
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10
Q

The neural basis of memory

A
  • Changes in neuronal wiring and synaptic connectivity in response to external stimuli- the stronger the connection the greater the chance of cells firing together
  • Modification in the efficacy of synaptic transmission- synaptic plasticity
  • Triggered by neural activity and production of second messengers
  • Can result from alterations in existing synaptic proteins
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11
Q
A
  • We need both the somatosensory system and auditory system to both converge on another neurone to produce a memory
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12
Q

The hippocampus

A
  • Rats hippocampus takes up a large portion of brain so there capacity for learning is relativly high
  • All soma of the neurones line up, all axons from cortex synapse into dendrites
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13
Q

An increase in the strength of a synapse after strong stimulation is called Long Term Potentiation (LTP)

A
  • Titianic stimulus (lots of stimulus in a short amount of time)
  • Or many synapses converging at once to give a large stimulation (EPSP)
  • Both of these cause Long-Term Potentiation (LTP)- raising the strength of the synapse for a long time such as for life
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14
Q

So why does the EPSP become larger

A
  • Increased excitability of post-synaptic cells- t
  • Increased number of AMPARs
  • Increase glutamate release- NMDAR stimulation
  • Formation of new synapses
  • Dependent on age- lose the ability to form memory by some pathways
  • All of these- depending on circumstances
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15
Q

Properties of NMDAR LTP (Long-term potentiation)

A
  • LTP is synapse-specific- Activity between 2 cells may only occur at one synapse
  • It is induced by NMDAR activation
  • It is expressed by AMPAR (the bigger EPSP)
  • It is maintained by changes in the number of post-synaptic AMPAR and structural changes (proteins)
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16
Q

Long-Term Potentiation

A
  • Enhancement of synaptic strength of stimulated synapses lasting many weeks (stimulation 100Hz, 1a)
  • Input specific
  • Displays co-operativity synapses must be active at the same time as neurons are strongly depolarised
  • The mechanism involves both pre and post-synaptic elements
17
Q

LTP INDUCTION has a threshold

A
  • There is a threshold for the establishment of long-term potentiation
  • The low rate of stimulation does not depolarize membrane sufficiently- low-level activity can actively reduce the strength of the synapse
  • EPSP produced by a high rate of stimulation summate and reach the threshold
18
Q

LTP is blocking by NMDAR antagonist and by removing Ca2+

A
  • Ketamine, Phencyclidine (PCP)
19
Q

The NMDAR in LTP- how does it sense pre and post-synaptic activity

A
  • NMDAR sense glutamate- pre-synaptic release
  • NMDAR sense depolarisation- Post-synaptic activity
  • Dual Gated system
  • The NMDAR is a coincidence detector
20
Q

LTP maintenance- AMPAR insertion

A
  • NMDAR opens
  • Ca ion enters and activates CAMK-II
  • Linking proteins attach to CAMK-II- Scaffolding proteins pull vesicles to the surface
  • AMPAR delivered to the membrane in vesicles
  • Additional AMPA receptors inserted in the membrane
    *
21
Q

AMPAR insertion- ‘silent’ synapses

A
  • Initially, synapses may have the only NMDAR
  • If there is sufficient depolarization from a neighbouring synapse, they may become ‘Unsilenced’ and AMPARs inserted into the membrane
  • Only NMDAR means no matter how much glutamate occurs there is no stimulation = NO depolarisation (AMPA needs to act first to depolarise to allow NMDAR to activate)
  • If we have enough depolarisation at neighbouring synapses that can be enough to shift Mg from NMDAR and AMPA receptors will be inserted hence that synapse can now be depolarised
22
Q
A
  • Very active dendritic spines can multiply (lumps on dendrites that form post-synapse)
  • Spines are the physical correlate of memory
  • Not enough activity can cause spines to die (this is why we have to constantly revise for exams because as activity of this synapse decreases it dies)
    *
23
Q

The Morris Water Maze

A
  • Before training- the path is long, slow and random
  • After training- the path is short and direct- grid cells fire in a particular way (synchronize) to map out the maze or path
    • Role of place cells- O’Keefe UCL Noble Prize Physiology 2014
  • Lesion of hipposampus or AP5
    • The training has no effect, path is long, slow, random
24
Q

The Morris Water Maze

A
  • Rat trained to swim through opaque water to find hidden platform
  • Rats hate swimming
  • Path of the swim is initially long
  • Path gests shorter when rat memorises location of the platform
  • Blocking NMDAR in a living rat with AP-5 or MK-801 blocks effect of training
  • NMDAR are involved in making real memories
25
Q

The reverse process-LTD

A
  • Long-term depression
  • Also NMDAR dependent
  • Non-coincident activity reduces EPSP size
  • Synapses constantly under pressure to get stronger or weaker
  • This forcing of synapses to reduce there activity EPSP without constant activation (so reduce memory) is known as homeostatic plasticity

PH3501- Neuropharmacology (28 decks)

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