Molecular & Cellular Bases Flashcards
What are the two main forms of learning that can be investigated?
Procedural - behaviour change/acquisition. Simple pathways that link sensations to movements. Easy to study.
Declarative - knowledge acquisition (mediated by the hippo). Difficult to study.
What are the two parts of procedural learning?
Non-associative learning - habituation, sensitisation.
Associative learning - classical conditioning, operant conditioning.
What is a habituation?
Decrease in the strength or occurrence of a behaviour due to the repeated exposure to the stimulus that produces that behaviour.
What is a sensitisation?
Increase in the strength or occurrence of a behaviour due to exposure to an arousing/noxious stimulus.
What are the main levels of analysis?
Molecular & cellular - behavioural & cognitive neuroscience.
With increased knowledge = increased ethical dilemma.
How did aplysia contribute to non-associative learning (invertebrate models of learning)?
Aplysia = snails.
Kandel intensively studied them.
Giant neurons that could be easily isolated to form mini brains.
Gil withdrawal - reflex in aplysia. Stimulation of the siphon leads to a protective/defence reflex to withdraw the gil. Only 2 neurons involved.
Snail learns and new synaptic connections are formed - LTM.
Where does habituation take place?
At synapse between sensory and motor neuron.
Neurotransmitter release at pre-synapse gets attenuated. Occurs at post-synapse - post-synapse neuron response gets weaker.
How do chemical synapses work?
- Vesicle docked at active zone.
- AP arrives, voltage gated Ca+ channels open.
- Exocytosis occurs - neurotransmitters released into cleft.
- Neurotransmitter caused transmitter-gated ion channels to open. Na+ rushes into cell - depolarisation.
- Used vesicles are recycled (endocytosis).
Where does sensitisation occur?
Sensory neuron and motor neuron synapse.
How does sensitisation occur?
- AP at terminal button of neutron L29 - release of serotonin.
- Serotonin receptors at terminal button of sensory neutron activated - cascade of molecular dynamics - activation of protein kinase A in sensory neuron.
- Protein kinase A blocks part of the K+ (potassium) channels in sensory neutron.
- Blocking of K+ channels. Prolonged action potentials at terminal button of sensory neuron.
- Longer APs - stronger influx of calcium into sensory neuron’s terminal button.
- More calcium influx = more vesicles will release NT into synaptic cleft between sensory + motor neurone.
- More NTs - stronger response at motor neuron.
Sensitisation shares the same neural mechanism with which process?
Classical conditioning.
Quantitative difference - classical > sensitisation.
More amplified neural response.
Who discovered classical conditioning?
Pavlov.
Who discovered operant conditioning?
Thorndike, Skinner.
How does classical conditioning in the aplysia work?
When CS and UCS are paired - Ca(2+) streams into terminal button of sensory neutron when cAMP is synthesised. Much more active protein kinase A than during sensitisation - more K+ channels blocked, longer AP, stronger response at motor neuron.
When does LTP occur in the hippocampus (vertebrate models of learning + memory).
LTP occurs with high frequency stimulation of Schaffer collaterals.
What are the 2 types of glutamate-gated ion channels on the post-synaptic membrane?
AMPA receptors (sodium channel) and NMDA receptors (sodium + calcium channel).
AP arrives at a Schaffer collateral - glutamate is released.
NMDA receptors - blocked by magnesium ion unless glutamate binds to receptors and post-synaptic is depolarised.
Glutamatergic synapses - using NT glutamate. Excitatory. Most common type in CNS.
What does an influx of Ca(2+) trigger?
An action potential.
Explain how LTPs occur.
- Simultaneous AP at presynaptic axon terminal buttons - depolarisation of postsynaptic membrane.
- Glutamate + depolarisation of dendrite. Magnesium blocks NMDA receptors released - influx of calcium. Calcium = relocation of new AMPA receptors to post-synaptic membrane = increased likelihood that AP will be generated.
- More sodium channels at post-synaptic membrane (AMPA) + more vesicles filled with glutamate at terminal button - synapse much more efficient.
How does long-term depression occur (vertebrate models of learning + memory)?
Low frequency stimulation of Schaffer collaterals = long-term reduction of EPSP in CA1.
Without strong NMDA receptor activity - weak influx of calcium - AMPA receptors are lost (because not being used). Synapse becomes less effective.
How does LTP lead to long-term memory?
Input has different sensory qualities. Overtime the pairing of these cause an increase response of neutron - LTP.
Frequent pairing - increase in AMPA receptors at postsynaptic membrane.
How does LTD relate to long-term memory?
Forgetting the memory, undoing the association.
What is Hebbian modification?
Neurons which fire together, wire together. Neurons which fire out of synch, lose their link.
How does Hebbian modification relate to LTPs?
Strengthening of cell assemblies through LTP. One part activated = whole assembly activated.
What immediate effects does LTP lead to?
New AMPA receptors.
What delayed effects does LTP lead to?
Protein synthesis and regulation of gene transcription.
Both trigger synaptic growth.
What do protein synthesis inhibitors do to LTPs?
Reduce LTPs.
Protein synthesis = prolongs effect of LTP - TM.
Protein synthesis inhibitors lead to deficits in LTM. Evidence seen in mice (Fioriti).
When does protein synthesis occur?
During formation of LTM.
What is protein synthesis regulated by?
CREB (c-AMP response element binding) protein.
What does CREB-2 do?
Inhibits gene expression.
What does CREB-1 do?
Displace CREB-2.
Phosphorylated CREB-1 initiates transcription.
Both of these are induced by LTP (long-lasting).
