260-2017-11-29-memory€¦ · in-class lab next mon review for exam 4 next wed exam 4, mon 12/11,...
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260-2017-11-29-memory2017-11-28 09:48:45
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Prelude
Memento Original 35 mm Anamorphic Trailer (HD) (CC)
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Today's topics
Biological basis of learning & memory·
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Coming up…
Quiz 4, review Exam 3 on Fri
In-class lab next Mon
Review for Exam 4 next Wed
Exam 4, Mon 12/11, 12:20-2:10 pm in 302 Boucke
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How do synapses change strength?
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Donald Hebb's Insight
(Hebb, 1949, p. 62)
(Lowell & Singer,1992, p. 211).
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'Hebbian' learning via NMDA receptor
receptor (NMDAR)
'Coincidence' detector
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Sending cell has released NT
Receiving cell is/has been recently active
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Example mechanism for 'Hebbian' learning
Chemically-gated AND
Voltage-gated
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Ligand- (glutamate/aspartate + glycine) gated
Sending cell active
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or ion 'plug' removed underdepolarization
& influx; outflux
Receiving cell responds
- Zn++ Mg++
- Na+ Ca++ K+
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NMDA receptor figure
https://upload.wikimedia.org/wikipedia/commons/thumb/0/00/Activated_NMDAR.svg/220px-Activated_NMDAR.svg.png
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NMDA receptors contribute to associativelearning
Associate (link)·
Concept A -> Concept B
Neuron A -> Neuron B
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Donald
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Donald
Trump
Duck
Draper
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NMDA clinical significance
(Alzheimer's Disease treatment) blocksNMDAR
Implicated in effects of (PCP)
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Controls over-activation and excitotoxicity?- Ca++
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Link to glu hypothesis of schizophrenia?-
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NMDA clinical significance
is NMDA receptor antagonist
Analgesic effects of nitrous oxide (laughing gas; NO)
Ethanol inhibits (Ron et al., 2011)
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anesthesia, sedation pain relief
possible short-term relief for depression
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Long-term potentiation (LTP)
https://upload.wikimedia.org/wikipedia/commons/thumb/b/b9/LTP_exemplar.jpg/800px-LTP_exemplar.jpg
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Long-term potentiation (LTP)
Increase in synaptic strength based on recent activity.
But how to learn/remember "causal chains"?
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e.g., lightning THEN thunder
unusual food THEN indigestion
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Spike-timing-dependent plasticity
(Caporale and Dan 2008)
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Spike-timing-dependent plasticity
(Caporale and Dan 2008)
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Spike-timing-dependent plasticity
A before B: strengthen A->B
A after B: weaken A->B
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Lasting changes in neural firing, connectivity-
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How does LTP (& LTD) work?
NMDA receptor one molecular mechanism forimplementing LTP, LTD and spike-timing-dependentplasticity
Ca++ entry triggers biochemical cascade
Existing (AMPA) glutamate receptors made to stayopen longer
New AMPA Glu receptors synthesized, inserted intopostsynaptic membrane
Change in quantity of glutamate releasedpresynaptically
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Dimensions of stored info
Memory of what?
Memory of when?
Memory for how long?
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Facts/events/places vs. skills-
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Immediate vs. distant past-
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Seconds vs. years-
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Summary thus far
Learning and memory involve changes in neuralfiring, circuitry
Hebbian learning a type of associative learning
NMDA receptor as coincidence detector
Different types of information stored in differentbrain systems
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Molecular basis of one form of long-termpotentiation (LTP)
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Disorders of memory
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Patient HM (Henry G. Molaison)
Intractable/untreatable epilepsy
Bilateral resection of medial temporal lobe (1953)
Epilepsy now treatable
But, memory impaired
Lived until 2008
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Brenda Milner tells the story
Brenda Milner, Neuropsychologist
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Amnesia
Acquired loss of memory
≠ normal forgetting
Note: computers don't forget
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HM's amnesia
Retrograde amnesia
Severe, global anterograde amnesia
But, skills (mirror learning) intact
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Can’t remember 10 yrs before operation
Distant past better than more recent
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Impaired learning of new facts, events, people-
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Types of amnesia
Retrograde ('backwards' in time)
Anterograde ('forward' in time)
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Damage to information acquired pre-injury
Temporally graded
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Damage to information acquired/experiencedpost-injury
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What it's like
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Other causes of amnesia
Disease
Korsakoff’s syndrome
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Alzheimer’s, herpes virus-
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Result of severe alcoholism
Impairs medial thalamus & mammillary bodies
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Patient NA
Fencing accident
Damage to medial thalamus
Anterograde + graded retrograde amnesia
Are thalamus & medial temporal region connected?
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Spared skills in amnesia
Skill-learning
Mirror-reading, writing
Short-term memory
“Cognitive” skills
Priming
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What does amnesia tell us?
Long-term memory for facts, events, people
≠ Short-term memory
≠ Long-term memory for “skills”
Separate memory systems in the brain?
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Next time…
Quiz 4
Go over Exam 3
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References
Caporale, Natalia, and Yang Dan. 2008. “Spike Timing-Dependent Plasticity: A Hebbian Learning Rule.” 31. Annual Reviews: 25–46. doi:10.1146/annurev.neuro.31.060407.125639.
Squire, Larry R. 2004. “Memory Systems of the Brain: A Brief History and Current Perspective.”, Multiple Memory Systems, 82 (3): 171–77.
doi:10.1016/j.nlm.2004.06.005.
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