• Biological basis of learning & memory

• 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

When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficacy, as on of the cells firing B, is increased. (Hebb, 1949, p. 62)

Neurons that fire together wire together. (Lowell & Singer, 1992, p. 211).

• N-methyl-D-aspartate receptor (NMDAR)
• 'Coincidence' detector
  • Sending cell has released NT
  • Receiving cell is/has been recently active

• Chemically-gated AND
  • Ligand- (glutamate/aspartate + glycine) gated
  • Sending cell active
• Voltage-gated
  • \(Zn^{++}\) or \(Mg^{++}\) ion 'plug' removed under depolarization
  • \(Na^+\) & \(Ca^{++}\) influx; \(K^+\) outflux
  • Receiving cell responds

• Associate (link)
  • Concept A -> Concept B
  • Neuron A -> Neuron B

• Trump
• Duck
• Draper

• Memantine (Alzheimer's Disease treatment) blocks NMDAR
  • Controls over-activation and \(Ca^{++}\) excitotoxicity?
• Implicated in effects of phencylidine (PCP)
  • Link to glu hypothesis of schizophrenia?

• Ketamine is NMDA receptor antagonist
  • anesthesia, sedation pain relief
  • possible short-term relief for depression
• Analgesic effects of nitrous oxide (laughing gas; NO)
• Ethanol inhibits (Ron et al., 2011)

• Increase in synaptic strength based on recent activity.
• But how to learn/remember "causal chains"?
  • e.g., lightning THEN thunder
  • unusual food THEN indigestion

• A before B: strengthen A->B
• A after B: weaken A->B
• Neural Plasticity
  • Lasting changes in neural firing, connectivity

• NMDA receptor one molecular mechanism for implementing LTP, LTD and spike-timing-dependent plasticity
• Ca++ entry triggers biochemical cascade
• Existing (AMPA) glutamate receptors made to stay open longer
• New AMPA Glu receptors synthesized, inserted into postsynaptic membrane
• Change in quantity of glutamate released presynaptically

• Memory of what?
  • Facts/events/places vs. skills
• Memory of when?
  • Immediate vs. distant past
• Memory for how long?
  • Seconds vs. years

• Learning and memory involve changes in neural firing, circuitry
• Hebbian learning a type of associative learning
• NMDA receptor as coincidence detector
  • Molecular basis of one form of long-term potentiation (LTP)
• Different types of information stored in different brain systems

• Intractable/untreatable epilepsy
• Bilateral resection of medial temporal lobe (1953)
• Epilepsy now treatable
• But, memory impaired
• Lived until 2008

• Acquired loss of memory
• ≠ normal forgetting
• Note: computers don't forget

• Retrograde amnesia
  • Can’t remember 10 yrs before operation
  • Distant past better than more recent
• Severe, global anterograde amnesia
  • Impaired learning of new facts, events, people
• But, skills (mirror learning) intact

• Retrograde ('backwards' in time)
  • Damage to information acquired pre-injury
  • Temporally graded
• Anterograde ('forward' in time)
  • Damage to information acquired/experienced post-injury

Every day is alone in itself, whatever enjoyment I’ve had, and whatever sorrow I’ve had…Right now, I’m wondering, have I done or said anything amiss? You see at this moment, everything looks clear to me, but what happened just before? That’s what worries me. It’s like waking from a dream. I just don’t remember.

• Disease
  • Alzheimer’s, herpes virus
• Korsakoff’s syndrome
  • Result of severe alcoholism
  • Impairs medial thalamus & mammillary bodies

• Fencing accident
• Damage to medial thalamus
• Anterograde + graded retrograde amnesia
• Are thalamus & medial temporal region connected?

• Skill-learning
• Mirror-reading, writing
• Short-term memory
• “Cognitive” skills
• Priming

• Long-term memory for facts, events, people
• ≠ Short-term memory
• ≠ Long-term memory for “skills”
• Separate memory systems in the brain?

• Quiz 4
• Go over Exam 3