• Biological basis of learning & memory

• Quiz 4, review Exam 3 on Thursday
• (Fun!) In-class lab next Tuesday
• Review for Exam 4 next Thursday
• Exam 4, Thursday 5/2, 4:40-6:30 pm in 112 Buckhout

• 1e12 neurons
• 1e3 synapses/neuron
• 1e15 synapses or 1.25e14 bytes
• 1e9 gigabyte, 1e12 terabyte, 1e15 petabyte

http://www.scientificamerican.com/article.cfm?id=what-is-the-memory-capacity

"Entirety of a human's lived experience could fit on a flash drive."

• Random Access Memory (RAM), short-duration storage
• Hard-disk/flash drive storage, long-term duration
• Addressable (location '010101')

• {text, sounds, images, video, data} all in binary [0,1] format
  • 00110000 == 48 (the number)
  • 00110000 == '0' (the character zero)
• Write once, read many times

• Computers have separate memory stores; brains store info everywhere
• Computers have addressable memory; brain memory??
• Computer memory can be non-volatile; brain memory??

• A: Acquisition of new or change in existing knowledge, skills, …
• Non-associative
  • \(A(t+1) = f(A(t))\)
  • Habituation (\(\dot f < 0\)), sensitization (\(\dot f > 0\))

• Associative
  • A -> B
  • Classical & operant/instrumental conditioning
  • Sequence, observational, episodic, semantic

• A: Information encoding, storage, retrieval
• Dimensions
  • Short vs. long-term
    • Working memory ~ short-term maintenance for guiding action

• Dimensions
  • Explicit (declarative: semantic vs. episodic) vs. implicit (procedural)
  • Retrospective (from the past) vs. prospective (to be remembered)
  • Recognition (familiar or novel) vs. recall

• Changes in patterns of neural activity
• Changes in connectivity
  • New synapses
  • Altered synapses (strengthened or weakened)

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 NMDA-R
  • Controls over-activation and \(Ca^{++}\) excitotoxicity?
• Implicated in effects of phencylidine (PCP)
  • Link to glu hypothesis of schizophrenia?

• Ketamine is an NMDA-R antagonist
  • anesthesia, sedation pain relief
  • short-term relief for depression
• Linked to analgesic (pain-relieving) 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

• Quiz 4
• Go over Exam 3