Memory Flashcards
What are the two ways of testing long-term memory?
What are the 3 components of memory/learning?
In what sense is the nervous system ‘plastic’?
Where are memories initially stored and how do they become part of long-term memory?
How do excitatory neurones become stronger?
Weaker?
Why is this?
What is short term memory shown in?
Declarative (recollection) and non-declarative (performance - riding a bicycle)
Acquisition, retrieval and extinction/erase (amnesia)
Ability of nervous system to change structure, function & connections in response to stimuli
Hippocampus - synapses of excitatory neurones form new circuits
When neurotransmitter release at a pre-synapse repeatedly correlates with the firing of an action potential (post-synaptic firing)
Release of a neurotransmitter fails to cause post-synaptic firing of action potential
Sum of the post-synaptic potential does not overcome the threshold required for depolarisation & the production of an action potential
Humans & higher animals
How can you test spatial learning in rodents?
What is the watermaze experiment?
How is the platform & rodent positioned?
How did the rodents perform the task?
What happens to the mean escape latency over 7 days of training?
What is a probe trial?
What will happen to the rodent on day 7 of training with a probe trial?
Learn a location/path in a maze, measure time taken to find correct location in training & then test whether the animal is searching in the trained location
Test of spatial learning - relying on rodents having to find a submerged platform from different locations in milky water
Platform at same location
Rodent positioned randomly
Distant cues e.g corners - if they were covered i.e with a curtain they could not perform the task
Takes fewer & fewer seconds & by day 7 almost swims directly to platform
Where the platform has been removed
Will still swim where the platform would have been
How is information stored in the nervous system?
How is the nervous system going to change in short term learning?
What about long-term?
Where are excitatory synapses located on the neurone?
What is seen on this structure?
How can ‘synapses’ be visualised in experiments?
What two neurotransmitters are involved in fast synaptic transmission, what are the receptor types & what kind of result does this cause?
How is the strength of a synapse determined?
Connections between neurones/synapses in distributed manner - stored in a neural network in string of synapses with precise info in precise locations
Changing of properties of existing synapses
Possibly more addition/removal of synapses
At the end of spines on the dendrites (projections) of the neurone
Part of it pre-synapse, and part of it post-synapse
Immunofluorescent staining (antibodies & fluorophores) of the spines
Glutamate with glutamate ion-ligand receptors & depolarisation (excitatory)
GABA with GABA-A receptors (ion-ligand) & hyperpolarisation (inhibitory)
Larger action potential & more receptors - post-synaptic
What are the 2 drugs that cause amnesia & what receptors do they act on?
What are both receptors?
- Ketamine is antagonist of NMDA receptors
- Benzodiazepines (shorter half life) is modulator of GABA-A receptors
Ligand-ion gated channels - faster transmission at synapses
What happens when GABA is released & binds to the GABA-A receptor on the post-synaptic neurone?
What can this mechanism lead to?
What do benzodiazepines do at the GABA-A receptors?
What happens to the dose response curve after the addition of benzodiazepines to GABA/agonist?
What happens to E50 and E100?
What is ketamine to the NMDA receptors?
What happens to E50 and E100?
What is ketamine used in?
What is a compound similar to ketamine?
What is a competitive antagonist of NMDA receptors? How is it different?
What happens on increasing concentration of competitive antagonist with agonist on the dose response curve?
Why is this drug not used in humans?
Influx of Cl- into the post-synaptic neurone - causing hyperpolarisation & hence inhibitory mechanism & reduced activity
Amnesia
Bind at second site & undergo allosteric regulation enhancing the binding of GABA
Dose response curve shifts to the left on increased concentration of the allosteric modulator (benzodiazepines)
E50 decreases (more potent) but E100 stays the same
Non-competitive antagonist (binds to a different site but produces basal response) - channel blocker preventing entry of Na+ & Ca2+ & exit of K+
E50 hasn’t changed much but E100 maximal response decreases
Veterinary anaesthesia
MK801 - non-competitive antagonist
AP5 - binds to the post-synaptic NMDA receptor preventing binding of glutamate
E50 increases of agonist (less potent) but E100 stays the same
Cannot cross the BBB (unlike ketamine & MK801)
How is the NMDA receptor normally inhibited on the post-synaptic membrane? (preventing excitation)
What is the size of depolarisation dependent on? 3 things
How is the synapse strength reflected?
What neurotransmitter does both AMPA-R & NMDA-R respond to?
Under resting potentials, what are the conditions of both receptors?
What happens to the NMDA-R receptor under depolarisation?
Therefore why is NMDA-R described as coincidence detectors?
Mg2+ sitting in the channel - blocking it
- Number of post-synaptic receptors
- Amount of neurotransmitter released
- Intrinsic properties of receptor - size of current after 1 receptor being activated
Size of post-synaptic response
Glutamate
AMPA-R channel is open and NMDA-R channel is blocked by Mg2+
Depolarisation (+ve) of post-synaptic membrane removes Mg2+ due to electric forces to allow Ca2+ & Na+ influx
Requires presence of glutamate and post-synaptic depolarisation to remove Mg2+
What signal from the NMDA-R provides a signal for AMPA-R?
How does it do this?
Why does depolarisation caused by AMPA-R not cause the activation of the NMDA-R?
How can you increase the likelihood of the Mg2+ being removed for NMPA-R activation?
What is LTP?
What is the LTP (long-term potentiation) Experiment?
What happens after the high frequency stimulation?
What is produced at the 20 minute mark?
How can this increase be blocked?
Ca2+ leading to increased number of AMPA-R in post-synaptic membrane
Activates CaMK 2 (Cam kinase 2) leading to increased AMPA-R
AMPA-R kinetics is much faster - such there is little overlap (1-2ms) such that it is not sufficient time frame for depolarisation & Mg2+ to be removed
Increase the frequency of action potentials from the pre-synaptic neurone - stronger & longer lasting depolarisation sufficient for activation of NMPA-R
Where synapses become stronger from repeated activation - mechanism underlying memory & learning
- Measure EPSP (action potential in post-synaptic neurone) every 10 seconds for 20 minutes = 0% baseline
- Then after 20 minutes apply 1 second stimulus of 100 pulses & measure EPSP
Post-synaptic site responds & EPSP (excitatory postsynaptic potential) is larger & remains stable until ~80 minutes
Long lasting potentiation
Ketamine or AP5 - the basal level
How was the hippocampus discovered to be responsible for declarative short-term to long-term memory consolidation?
What did impairment of the hippocampus do in rodents?
What is the 3 step linear tri-synaptic circuit of excitatory synapses in the hippocampus?
What is associated with the CA1 synapses?
How can LTP be studied in the hippocampus? 3 ways
What are the 3 properties of LTP?
HM had epilepsy & had it removed - could still recall childhood memories but could not recall short term memory
Impairment in spatial memory like in the watermaze task - hippocampus contains place cells (becomes active in hippocampus when animal enters specific location)
- Input received at cortex
- Synapse at dentate gyrus & granule cells in dentate gyrus extend axons to CA3 of hippocampus
- Synapse to CA3 neurones & neurones extend to CA1 area to CA1 synapse
LTP at this synapse which is NDMA-R dependent
- Brain slices
- Anaesthetised animals
- Free-moving animals
kk
- Input specific - induced & maintained at appropriately stimulated synapses - not neighbouring ones
- Persistence - maintained for prolonged time (hours-days) following brief stimulus
- Associative - requires concurrent events on both sides of the synapse - pre-synaptic glutamate release & post-synaptic depolarisation
