Hebbian And Synaptic Plasticity Flashcards
Importance of Donald Hebb
Two neurons become stronger synapsed with more use, stronger association
What is Hebb’s rule
Neurons that fire together, wire together
What is hebbian plasticity
Basic PRINCIPLE that learning and memory can occur due to changes in the strength of connections between neurons
- Hebb inferred the principle without knowing the mechanisms
What are the mechanisms for hebbian plasticity
Long-term potentiation (LTP)
Long-term depression (LTD)
Define homeostasis
Body’s ability to maintain a set point
Homeostatic plasticity function
Move neurons back to set point (original stage) after modification
What does continual excitation cause
Excitotoxicity
-mess up ATP production, mitochondria issues
Explain long-term potentiation
Synaptic activity increases future post-synaptic potentials
Or
Excitation at synapse determines greater excitability in the future
What/when was the first evidence of LTP
1973
Trains of high frequency APs led to increased EPSP
- prove EPSP increase in future after excitation at synapse
What is a high frequency value
50 Hz
How are synaptic experiments recorded
Electrode- pre synaptic neuron
Recorder- post synaptic neuron
How is LTP triggered
High sustained Ca in post synaptic neuron triggers LTP
- intracellular Ca signalling
What does LTP cause, what is this dependent on
Structural changes at the postsynaptic terminal
Dependent on glutaminergic receptors (AMPA/NMDA)
What kind of channels are NMDA and AMPA
NMDA- Ca channel (also permeable to Na, K)
AMPA- Na channel (also permeable to K)
What kind of receptors are NMDA and AMPA
Glutamate receptors
Explain LTP pathway for NMDA and AMPA (when there is a depolarizing signal)
Local depolarization removes Mg from NMDA (at RMP NMDAR is blocked by Mg)
Ca influx through NMDA (in postsynaptic membrane) activates intracellular CaMKII pathway (CaMKII is Ca dependent kinase)
Insertion of AMPAR in post synaptic membrane (inside neuron brought to surface) via vesicular fusion caused by kinase phosphorylation (now have more post synaptic channels, can generate larger EPSP)
Provide details for AMPAR
- tetrameric (4 subunits) can choose from GluA1-4
- central Arg provides specificity
- inward current at negative mV (Na)
- outward current at positive mV (K)
- without GluA2 inwardly rectifying
Provide main function of NMDAR
Trigger LTP: strong activation of NMDAR lead to large increase in postsynaptic Ca
Trigger LTD: modest activation of NMDAR leads to modest increase in postsynaptic Ca
AMPA and NMDA are non-selective ion channels so where is their reversal potential
Near zero (I vs V graph)
Draw the NMDAR and AMPAR current vs voltage graph
AMPA should have 2- with and without GluA2
Pg. 7 of Hebbian
How does LTD happen
Moderate Ca levels trigger PP2B and PP1
PP2B- calcineurin
PP1- protein phosphatase 1
These phosphatase s’ s remove P from AMPAR and recall receptors into postsynaptic cell via endocytosis
Receptors can be reused later
Explain molecular events that lead to increase in AMPAR during LTP
Transport of endosomes important for AMPAR insertion
- involves Rab, syntaxin, synaptotagmin, complexin
Laterally diffusing AMPAR must be trapped at nanodomains
- involves CaMKII and P-PDZ stargazin
Phosphorylation results in binding of stargazin to PSD-95
(stargazin and PSD-95 are structural proteins that physically anchor receptor to membrane)
Role of cadherens
Transmembrane proteins that tether the pre and post membranes together- physically strengthen synapse
EPSP outcome after increasing AMPA
Overall greater, same NMDA current and greater AMPA current
There is a comparative graph on pg 10
Result of hippocampus damage
Inability to make new memories
Importance of hippocampus and location
Connections critical for formation of long-term memories
- medial temporal lobe structure with well-characterized regions (Ca1, CA3, dentate gyrus)
Patient H.M.
Bilateral loss of hippocampi produces anterograde amnesia or inability to form new memories
What 4 structures form a neural circuit
CA1
CA3
DG (dentate gyrus)
EC (entorhinal cortex)
Function of EC
Entorhinal cortex is a bridge between the hippocampus and the cortex
Describe pathway of 4 structure neural circuit
EC gets input from cortex and gives it to hippocampus
Dentate gyrus receives input from EC and projects to CA3
CA3 receives input from DG and from EC
CA1 major output goes to layer V of EC
What can stimulation to EC cause
Repeated stimulation of EC cells that project to DG leads to increased EPSPs in DG (consistent w Hebbian principles)
Requirements for hippocampus LTP
- input specificity: only activated synapses will potentiate (get LTPed)
- cooperativity: enough presynaptic axons must fire coincidentally (at same time) to activate the post synaptic neuron (to get LTP)
Values for frequency levels
50 Hz - high
10 Hz - medium
1 Hz - slow
Experiment for hippocampal plasticity
Measure post synaptic EPSP. Induce LTP in lab
Test and control pathway. Stimulus to Schaffer collaterals (using different synapses on CA1 neuron for two conditions)
CA3 neurons project to CA1 neurons
Electrode in CA3 Schaffer collaterals provide depolarization
Recording electrode in CA1
Test pathway- 10 Hz frequency paired with post synaptic depolarization (paired pulse protocol)
Control pathway- CA1 neuron never depolarized, constant 10 Hz amplitude, no EPSP generation
When does LTD occur
Long-term depression happens because of
- short term decreases caused by inactivation of Cav channels
- depletion of NT containing vesicles
What is LTD
Temporary decrease in post synaptic excitability
Factor that determines if a synapse will strengthen
Frequency of stimulation it receives
How does LTD occur
Activation of phosphatases that act on synaptic proteins to regulate synapse strength
- proteins: cadherins, catenins, PSD95
- phosphatases also remove P from AMPA cause endocytosis
Function cadherins vs catenins and PSD-95
Cadherins
- outside of cell, tether neurons at synapse
Catenins and PSD-95 (post synaptic density)
- intracellular, link AMPA to cytockeleton
Localizationism and connectionism: what? Key takeaway is they both are important for history of neurology
Localizationism (where in brain)- particular functions for particular regions or groups of neurons
Connectionism (neural circuit/connections)- particular functions for connected neurons
Does Hebbian plasticity prove Localizationism or connectionism
Connectionism
- provides a connectionist account of learning, memory, development
Where are memories stored? What does this prove?
Short term- hippocampus
Long term- cerebral cortex, thalamus (36 days after learning)
Explains why loss of hippocampus prevents new memories but old memories remain in tact
Shows that memories are plastic
Proof the brain is plastic
Trevor Greene- severed motor cortex but was able to rewalk
- following traumatic injury, functional brain responses can be remapped through new groups of neurons being recruited
How does plasticity change during development
Child- connections are stronger between neurons that are anatomically close but functionally unrelated
Teens/adults- connections are stronger between neurons that are functionally related but distant
Why are connections between neurons important
Learning and memory encoding
What does neural plasticity allow for
Education
Training
Recovery
Amount of connections at birth, 7, 15
Birth- few
7- most
15- less than7, synaptic pruning. LTD weakens unnecessary synapses
Snail experiments
Article and pg 20
Scientists made snails remember something that didn’t happen to them
1. Extract RNA from trained snails and put in untrained. Upon shock the untrained snails responded the same as the trained snails (siphon retract for long period)
2. Untrained snail brain cells in dish with trained RNA, shock neurons and saw them fire same was as trained neurons
