Learning + Memory Flashcards
What is learning?
= the strengthening of responses or formation of new responses to stimuli due to repetition or practice
What is memory?
= the storage and retrieval of knowledge gained through learning
What are the different forms of learning and memory?
Declarative / Explicit
= knowledge about facts and their meaning
= recalled consciously
Non-declaritive / Implicit
= knowledge about how to perform something
= recalled unconsciously
= can be associative or non-associative
= provides evolutionary advantages
What is associative vs non-associative implicit memory?
Associative:
= the association between two stimuli is learned
=e.g. classical conditioning = Pavlov’s paradigm (dogs)
= Unconditioned stimulus (US) = food
= Conditioned stimulus (CS) = bell
= when bell (CS) repeating paired with food (US) = becomes able to elicit salivation
= Conditioned Response (CR)
Non-associative:
= Habituation = decrease in response to a benign stimulus through repeated presentation of the stimulus
(e.g. wearing clothes = touch receptors become benign)
= Sensitisation = an enhanced response to multiple different stimuli after presentation with a noxious or intense stimulus
What are the fundamental questions to be asked in research?
How does learning occur?
How is memory encoded, stored and retrieved?
What genes / proteins are involved?
What are the cellular mechanisms / processes?
What areas / circuitry of the brain are involved?
What have neuromodulation studies in invertebrates shown?
= indicate that forms of implicit memory involve experience-dependent modulation of synaptic strength and structure
(= synaptic plasticity)
What are the differences between short, intermediate and long term memory?
Short term memory
= lasts minutes
= involves covalent modifications of pre-existing proteins at the synapse by kinases
(e.g. phosphorylation)
Intermediate term memory
= lasts hours
= involves new protein synthesis
= (BUT NOT mRNA synthesis)
Long term memory
= lasts days, weeks or more
= requires CREB-mediated gene expression
= requires new mRNA and protein synthesis
What is the Aplysia (sea snail) nervous system used as a model?
= has ~20,000 large identifiable nerve cells
= individual neurons can be identified and their electrical activity recorded (electrophysiology)
= neural circuits controlling behaviours have been defined
= behaviour most extensively studied is the gill and syphon-withdrawal reflex
What is an example of neuromodulation in Aplysia (sea snail)?
= natural predator is the spiny lobster
= responds to attack by closing gill and syphon, ejecting cloud of ink that repels and confuses lobster
= behaviour controlled by simple reflex circuit
= then sea snail is sensitised to future attack
= sensitisation involves modulation of synapses at sensory neurons (a learned fear response)
What are the cellular mechanisms of short and intermediate term memory formation in Aplysia?
- Serotonin released in viva / applied directly binds to cell surface receptors of sensory neurons
- = activates adenyl cyclase = promotes cAMP production
- = short term sensitisation (increase in synaptic strength of sensory to motor neuron connection)
- = short term facilitation (partially due to enhanced release of glutamate by sensory neuron)
- = also increase in sensory neuron excitability (due to depression of specific potassium channels)
- changes in cAMP and Ca = regulate kinase and phosphatase activity = control duration and strength of synaptic efficiency changes
Molecules involved in this synaptic plasticitity
= presynaptic PKA
= presynaptic calcium and CamKII
= presynaptic PKC
= postsynaptic calcium and CamKII
= recruitment of pre- / ?post-synaptic molecules to new sites
= enhances glutamate release from sensory neurons
What are the cellular mechanisms of long-term memory formation in Aplysia?
Long term plasticity contributing to learning involves:
- neurotransmitter release + short-term strengthening of synaptic connections
- equilibrium between kinase and phosphatase activities at the synapse
- retrograde transport from the synapse to the nucleus
- activation of nuclear transcription factors
- activity-dependent induction of gene expression
- chromatin alteration and epigenetic changes in gene expression
- synaptic capture of newly synthesised gene products
- local protein synthesis at active synapses
- synaptic growth and the formation of new synapses
- activation of pre-existing silent synapses
= location of these events moves from the synapse to the nucleus and the back to the synapse
= requires repeated stimulation
What is classical (associative) olfactory learning and memory in Drosophila?
= involves learning contingency between an odor (CS) and an aversive or appetitive stimulus (US)
(can be an escape response)
= conditioning requires activity of molecules that can integrate the 2 types of sensory information
= a form of adenyl cyclase performs this integration function (in the mushroom body neurons of the fly brain)
= dopaminergic neurons carry information about aversive stimuli (to MB neurons)
= octopaminergic neurons carry information about appetitive stimuli (to MB neurons)
= GABAergic neurons control ability to learn via inhibitory inputs
What are the mechanisms involved in aversive olfactory conditioning?
= CS information presented to MB neurons by Postganglion neurons (PNs)
= PNs release Ach at synapses with MB cells causing voltage-gated calcium channels to open
= increase in intracellular Ca = produces more calmodulin bound with Ca
= activates adenylyl cyclase = produces elevation in cAMP
= US information presented to MB neurons by PPL1/PPL2ab neurons = release DA onto MB neurons
= activation of DA receptors = increases cAMP levels through activation of a heterotrimeric G protein coupled to AC
= coincident activation of the CS and US pathways during conditioning
= synergistic increase in cAMP occurs = necessary info provided in MB for encoding the CS/US temporal coincidence
(relationship established)
What are the molecular mechanisms involved in appetitive olfactory conditioning?
= same CS pathway is induced in the MB neurons
= US info may be represented by octopamine release onto MB (also stimulates AC)
= DA neurons have role in appetitive conditioning (not fully understood)
= coincident application of CS and US produces subadditive increase in postsynaptic cAMP
EXTRA READING - DA neurons role
= DA neurons activated in response to rewarding stimulus
= releasing dopamine
= brain associates rewarding stimulus with the environmental cues (re-inforcing)
= can lead to a conditioned response (even in absence of reward itself)
