NEUR533 - Molecular mechanisms of learning and memory Flashcards
MUST READ THIS
LEARNING OUTCOMES
LEARNING OUTCOMES
What does the acquisition of short-term memory essentially require?
- Physical brain modifications caused by incoming sensory information
- Modifying synaptic transmission between neurons
What does long-term memory consolidation require?
New gene expression and protein synthesis
Flow of sensory information into long term memory
what animal was a lot of learning and memory studies conducted on in the early days?
Aplysia
Californian sea slug
Studies done in the 70’s
Advantages
- large brain
- simple brain
- large abdominal ganglia
- Neurons can be easily identified
-
Repeated stimulation =
- no changes presynaptically
- BUT sees changes in excitatory post-synaptic potentiation
= HABITUATION
SENSITIZATION CELLULAR MECHANISM - KNOW
What is neuron L29?
- secondary motor neuron
- Interneuron
- Activated by stimulation (electrical) in the head ganglia
- Released 5-HT
- Binds to GPCR
- Closes K+ channels
- Delays K+ repolarization
What does an increase in closing K+ channels do for an action potential?
- Shift to the right
- Longer repolarisation
- Increased VG Ca2+ channels
= Increased Ca+ influx
= Increase NT
= Increased post-synaptic potential
= Sensitisation
youtube this
Cellular mechanism of classical conditioning of the gill withdrawal reflex.
- Opens presynaptic Ca++ channels
- Ca++ influx
- Ca+ activates AdCy
- Changing nature of presynatpic terminal
- Stimulates L7 neuron
(needs to be paired by cAMP)
Structure of the cerebellar cortex - always understand
What are the 4 layers of the cerebellar cortex?
Molecular layer
Purkinje cell layer
Granule cell layer
White Matter
What do climbing fibres do?
Innovate a single purkinje neuron
Long term depression of synaptic transmission in cerebella cortex
A mechanism of LTD induction in the cerebellum
What do climbing fibres do?
- Activate Na+ channels
- Releases glu
- Activates VG Ca++ channels on post synaptic membrane
- Increases intracellular Ca+
(must be paired) - Large stimulatory activation prior to PKC
= FEWER post synaptic AMPA receptors
What does a reduction in AMPA receptors do to PSM
- LTD
- Reduction in PS excitation
- Only when parallel fibres and climbing fibres come together
What does the internalisation of AMPA receptors and LTD do intracellularly?
Getting rid of movements that dotn need
fine tuning of motor system
- Reduces errors in movement
LTS in the cerebellum - LEARN AND DRAW THIS GRAPH
What does the increase of internal Ca++ concentration do?
Increase AdCy
What does the increase in AdCy do?
Increase cAMP
Increase PKA
Increase phosphorylation
Increase gene transcription
What does the increase internal Na+ concentration and activation of PKC do PLUS combine with internal Ca++ concentration?
Internalise AMPA receptors
= Decrease openings of AMPA receptor channels
= Reduce LTP
= Initiate LTD
What increases the internal Ca++ concentration?
Strong depolarization of Purkinje cell dendrites
What is the area IT associated with?
visual area
FACIAL RECOGNITION
Memory storage of objects
Can every neuron form a memory of recent patterns of activity?
Yes
Responses to faces in the inferotemporal cortex (IT area)
remember IT = facial recognition
= Visual association
Distributed memory storage
Model of distributed memory
REMEMBER AND DRAW OUT THIS PATHWAY
KNOW: what is the first path of the trisynaptic circuit of the hippocampus?
- Entorhinal cortex -> dentate gyrus (perforant path) synapses
KNOW: what is the 2nd path of the trisynaptic circuit of the hippocampus?
- Dentate gyrus > CA3 (Mossy fibre) synapses
KNOW: what is the 3rd path of the trisynaptic circuit of the hippocampus?
- CA3 > CA1 (Schaffer collateral) synapses
KNOW: what is the complete path of the trisynaptic circuit of the hippocampus?
- Entorhinal cortex -> dentate gyrus (perforant path) synapses
- Dentate gyrus > CA3 (Mossy fibre) synapses
- CA3 > CA1 (Schaffer collateral) synapses
Who studied that high-frequency electrical stimulation (tetanus) of excitatory pathway produces LTP?
Bloss and Lomo
LTP in CA1 - know
LTP is only in association with input 1 - doesn;t change input 2
Mechanism of LTP at CA1
LTP in CA1 - KNOW AND LEARN
How long does it usually take for AMPA and NMDA receptors to activate kinases?
Minutes
how do kinases influence the AMPA receptor?
phosphorylates the AMPA receptor and keeps them open longer
or
Insertion of extra AMPA receptors
= LTP
e.g. from a significant event that needs to be remembered or learnt
CA++ imaging from single dendrite
Showing morphological change
Sprouting new dendritic spines
(induced LTP)
LTD - weakening of synapses
What is homosynaptic LTD?
- Synapses Weakened by weak depolarization
What i bidirectional plasticity governed by?
LTP
LTD
Spike timing-dependent plasticity
Mechanisms of LTD in CA1
What are the 2 receptors regulating homosynaptic LTD at Schaffer collateral-CA1 synapse?
- GPCR glu receptors (mGluRs)
- NMDA receptors
How do NMDA receptors increase LTD in CA1?
Rise in PS Ca++ to trigger LTD
Is LTP and LTD bidirectional regulation?
Yes
Is a rise in Ca++ needed for LTD and LTP?
Yes both need it
How Ca++ can trigger both LTP and LTD in hippocampus
HFS = high frequency stimulation
Egg carton model of AMPA R
Who did the first experiments with inhibitory avoidance and found NMDA -receptor processes in memory?
Morris
Who did genetic knockouts in mice deleting CaMK11 NMDA subunits and found hippocampal LTP and memory parallel deficits ?
TONEGAWA , Silva, and colleagues
Hippocampal __________ receptors play a key role in synaptic LTP and LTD and learning and memory
NMDA
Morris experiment
What does area IT abbreviate for?
Inferotemporal cortex
Synaptic homeostasis