Lecture 2 - Spatial Learning & LTP 1 Flashcards
1
Q
Learning
A
- learning is a change in behaviour that results from experience i.e. acquiring knowledge & skills through experience.
- corresponding physical change in the brain
- criteria for learning to occur should be the same as the neural mechanism
2
Q
pavlovian conditioning
A
- learning through association
- 2 stimuli link & generate a new behavioural response to a previously neutral stimulus
- NS paired with a US triggers a UR
- NS becoems a CS and trigger is now a CR
3
Q
neural basis of learning
A
- learning is a psychological process of pairing events together
- looking for a neural mechanism that would allow associations to be formed
4
Q
hippocampus
A
- processes multimodal sensory and spatial info
- loop of synaptic connections
> entorhinal cortex - main input
> CAI1 - main output
5
Q
pre-discovery of LTP
A
- kindling - a model of epilepsy where prior stimulation inc likelihood of neurons firing
- this logic applies to whether one stimulates and measures single neurons or thousands
- pre-synaptic and post-synaptic -populations must be segregated and readily identifiable
- Bliss & Lomo - applied this exp design to mammilian hipp
6
Q
suitable circuitry
A
- pre-synaptic and post-synaptic populations must be segregated and readily identifiable
- antanomy of hipp fits this
- Bliss and Lamo conducted this exp in anaesthetised rabbits & later work in isolated slices
- in hipp can stimulate cells from one pop of cells and measure effect on another set of cells.
- Results:
> EPSP (change in activity of a cell post stimulation) before high freq tetanic stim is not as larg as after tetanic stim. response inc in the post synaptic cell after
> This LTP is long term and can have long term effects on behaviour
> as a result of repeatedly stimulating neurons, connecting ones become more responsive
7
Q
key properties of LTP
A
- Long term
- LTP only occurs when firing of presynaptic neuron is followed by firing of postsynaptic neuron (two cells have to be firing at the same time) - this co-occurrence is critical for LTP and learning (known as hebb’s postulate for learning)
8
Q
the hebbian basis of memory
A
- if the synapse is active at the same time as the post synaptic neuron fires then physical changes to the synapse take place to strengthen it (fire together wire together)
- e.g. rabbits pair NS (tone) to give same blink response as puff of air does (UCR) - strong sensory and weak auditory neurons fire onto motor neuron to produce response.
- motor neuron synapses onto blink response and causes blink when puff of air occurs. when playing tone this auditory neuron is weak alone and not enough to create blink but after many trials with puff of air you get more ESPS changes which creates stronger synapse to create blink alone (no learning needed for co-occurrence)
9
Q
action potential (recap)
A
- glutamate is primary excitatory nt
- normal glutamate receptor sis AMPA receptor
- when glutamate binds to AMPA receptor, the recepir opens membrane channels and allows depolarisation (lets pos charged ions into cell)
- glutamate here carrys out the excitation.
10
Q
induction of LTP
A
- LTP studied at synapses with lots of NMDA receptors for glutamate
- NMDA receptor words maximally when post-synaptic neuron (e.g. blink) is partially depolarised (already has activity partially passing on from one cell to another) as well as glutamate binding to it
11
Q
NMDA receptor-linked channels: coincidence detectors
A
- only open in the presence of neurotransmitter and when post synaptic membrane is depolarised.
- therefore they act as a pre and post synaptic activity coincidence detector (both active at same time)
12
Q
NMDA receptor voltage sensitivity
A
The ion channel associated with the NMDA receptor is normally blocked by a pos charged magnesium ion
- the ion is no longer attracted to the cell once it is depolarised sufficiently
13
Q
a coincidence detector
A
- one cell depolarises (AP) & mg detaches as no longer has charge to stay in place = no coincidence to detect
- glutamate released & can bind to receptor and open green channel (pos ions already entering)
- NMDA receptors are selective to only letting calcium in
- only when pre and post synaptic cell are active will calcium be able to enter neuron (key part of LTP
14
Q
how is the synapse more efficient
A
- the induction mechanism (NMDA receptor) is post-synaptic
1. post synaptic changes - AMPA receptors - Muller et al (1988) - AMPA receptor (non fussy glutamate) antagonist prevented LTP expression. no. AMPA receptors inc = cell becomes more responsive to glutamate so more ions enter and easier to depolarise
- Tocco et al (1992) - LTP changed ampa not nmda receptor no.
- AFTER induction of LTP potentiation effect was abolished by blocking AMPA not NMDA receptors = LTP requires AMPA
2. post-synaptic changes - protein synthesis - blocking protein synthesis by inhibiting transcription after stimulation prevents LTP
- LTP needed for proteinsynthesis which may inc no. proteins which changes structure of cell
15
Q
post-synaptic structural changes effects
A
- LT inc in AMPARs
- growth of new spines (new synapses)
- enlargement of spines (synapses)
- splitting of synapses
= more enlarged postsynaptic area so more responsive to glutamate
16
Q
pre-synaptic effects of structural changes
A
- radioactively label glutamate precursors
- measure synaptic radio-activity before and after LTP
- more radioactivity in synapse after LTP (dolphin et al 1982)
- enhanced glutamate after LTP - have a combo of post synaptic cell being more responsive to glutamate and more glutamate being released in presynaptic cell = glutamate release easier
17
Q
how can the presynaptic cell know?
A
- the induction mechanism (NMDA receptor) is in post-synaptic cell
- after NMDA receptor activity the signal must be sent from the post-synaptic to pre-synaptic cell - not only has structural changes but also releases retrigrade transmitters (release post synaptically and go back to presynaptic cell)
- when calcium enters postsynaptic cell it activates the second messengers within the ce;; (kinase enzymes) = postsynaptic release of NO which acts as retrograde transmitter by being detected & inducing changes in presynaptic cell
18
Q
LTP summary
A
- LTP is process where synaptic connections become stronger with frequent activatoin:
> glutamate first released by AMPA receptos & NMDA currently blocked by magnesium ion
> when depolarises, magnesium moves (voltage dependent) and calcium enters
> leads to more AMPA receptors to occur and allows more pos glutamate in
> cell becomes more sensitive to glutamate so the cells wire together and connections become stronger = better able to cause AP in firing cell.
19
Q
the relation to learning and memory
A
- associative learning requires the formation of links between memories of stimuli
- LTP is a mechanism for the formation of links between neurons
20
Q
NMDA receptor-dependent LTP
A
- NMDA is a coincidence detector
- LTP occurs if these two things happen:
1. glutamate binds onto NMDA receptor
2. cell is depolarised
21
Q
hippocampus-dependent learning and LTP
A
- LTP is readily observed in the hippocampus
- hipp long associated with learning & memory & important in spatial learning
- prediction that LTP in hipp is necessary for spatial learning
22
Q
hippocampus and spatial learning
A
- MWM test
- Morris et al (1982) tested idea that mwm task would be hippocampus dependent.
- used rats with hippocampus lesions
- findings:
> sham lesioned preferred quadrant of pool that had the platform before
> hipp lesioned rats show no preference. not impaired on visual version but were impaired when they had to spatially navigate the platform.
> also tested learning about visual cues
> conclude mwm task is hipp dependent. but does it depend on hippocampal LTP? - Morris (1989) is LTP necessary for hipp-dependent spatial learning?
> infused AP5 - NMDA receptor antagonist in rats brain
> rats given control drug preferred training quadrant whereas AP5 rats showed no preference (all over the place)
> AP5 did not impair retention of previously learned spatial info, but impaired new spatial learning = LTP necessary - BUT rats with AP5 also showed sensorimotor impairments too - seemed wobbly and may have impaured performance e.g. swimming & climbing rather than learning
23
Q
AP5 and spatial learning
A
- Bannerman et al (1995) - dissociated performance deficit from learning deficit.
> 2 watermazes one upstairs one downstairs. if pretrain to swim before AP5 this overcomes sensorimotor problem - Findings:
> AP5 impaired performance when there was no pretraining but not impair performance if rats had pretraining
> suggests LTP in hipp may not be necessary for spatial learning
