JULY 30 LEARNING & MEMORY
Kalat: Chapter 13

• Types of Memory
  • Short term memory (STM): immediate memory for an event/stimulus that has just occurred
  • Long term memory (LTM): memory for an event that is not currently in one's attention; must be retrieved from storage
    • Consolidation of LTM. STM --> LTM?
      • Most information in STM is forgotten
      • LTM is improved by many meaningful associations
      • Exciting experiences release Epi (adrenaline) to arouse the SympNS and increase the amount of glucose to the brain
    • Time: increasing time in STM increases chances of STM-->LTM
  • Explicit/Declaritive Memory: facts or specific events; tested directly (YES, 1492)
  • Implicit/Procedural Memory: conditioned responses; learned motor skills ; perceptual learning; tested indirectly (maze learning)
    • priming: hearing (learning & recalling) words increases the chance that you use them
• Representations of Memory
  • Diffuse Representation of Memory: Karl Lashley
    • Hypothesis 1: Equipotentiality - all cortical regions can mediate learning equally
    • Hypothesis 2: Mass Action - ability to learn is proportional to amount of cortex available
      • Engram: the physical representation of learning
    • Lashley was incorrect. Most learning and memory involves subcortical mechanisms rather than cortical
      • Cerebellum (Lateral Nucleus Interpositus)
      • Hippocampus
  • Localized Representation of Memory: Pavlov's Cortical Model
    • Hypothesis: The formation of new (psychological) associations create new cortical connections
    • Classical Conditioning - Pairing of stimulus and response leads to conditioned responses; species typical behavior; learning = assoc. between 2 stimuli (CS-CR)
    • Physiological correlate = strengthening CS-UCS connections => Hebb's rule
    • Hebb's concept of reverberating circuits. Building links with other memories.
      • Importance or meaningfulness:
      • Excitement of the memory. Does epinephrine facilitate memory?
    • The Hebbian Synapse: A synapse that is inc. effectiveness by simultaneous activity in the presynaptic and postsynaptic neuron.
      • How does the Hebbian synapse relate to learning?
        • Physical Changes
          • Changes in dendritic branching
          • Axon terminal may grow
          • Changes in glia
        • Chemical Changes
          • Increased or decreased transmitter release
          • Protein synthesis
    • Operant Conditioning - pairing of a response with a subsequent reward or punishment which will affect the likelihood of repeating that response in the future; learning = association between a stimulus & a response

• The Role of Specific Brain Regions in Learning and Memory
  • The Role of the Cerebellum in Learning and Memory
    • Cerebellum and Implicit (Procedural) Memory
      • Conditioned Response learning: Thompson - engram for classical conditioning
      • Learned motor skills, skilled habits
  • The Role of the Hippocampus in Learning and Memory
    • Hippocampus and Explicit (Declarative) Memory, etc.
      • Discriminative: can decide between L/R; low/high frequency
      • Configural Conditioning: cannot learn to response by making a combination of 2 or more stimuli
      • Spatial learning tasks: radial mazes
      • Cannot create Explicit/Declarative memory
        • Ex. H.M.
        • severe seizures; bilateral removal of hippocampus & amygdala
        • moderate retrograde amnesia: 1-3 years prior to surgery
        • severe anterograde amnesia: events after surgery
        • Implicit/Procedural memory is intact
        • Ex. Korsakoff's Syndrome- thiamin (B1) deficiency
        • Severe alcoholics
        • Degeneration of the mammillary bodies and dorsomedial thalamus (projects heavily to prefrontal cortex)
  • The Role of the Prefrontal Cortex in Learning and Memory
    • ventral prefrontal cortex: Preservation - repeatedly making the same response, even when they know to make another response
      • Ex. WI Card-Sorting Task (sort by color, number, shape)
    • dorsolateral prefrontal cortex (principal sulcus): spatial location
      • Ex. Delayed Response Task (keep location in STM than move)
  • Brain & Memory in Young and Old
    • Infant amnesia: tendency for people to recall few specific events before 4-5yo
      • Implicit memories may go further back than explicit memories
    • Infants & Elderly perform most poorly on hippocampal-dependent tasks (involving explicit memories)
    • Hippocampus is slow to mature and degenerates in ULd age
    • Prefrontal cortex also degenerates with age
    • Declining DA & norepinepherine (NE) synapses in the prefrontal cortex

• Do neurons learn?
  • The persistance of learning in decapitated cockroaches and isULated Aplysia nervous system demonstrates that relatively few neurons are needed for a system to show basic learning.
• Simple Learning in Aplysia - Marine invertebrate "Sea hare"
  • Demonstrates synaptic and neural mechanisms that mediate 3 kinds of simple learning: Habituation, sensitization, and classical (Pavlovian) conditioning.
  • Habituation in Aplysia - a decreased response to repeated harmless stimulus; not due to muscle fatigue
    • What physiological change accompanies habituation?
      • Decreased transmitter release by the presynaptic cell
      • The decreased response is specific to the eliciting stimulus.
  • Sensitization in Aplysia - an increased response to repeated intense stimulus
    • Increased transmitter release by the presynaptic (sensory) neuron due to...
      • Release of serotonin (5-HT) from fascilitating neuron onto the sensory neuron's presynaptic terminal
      • 5-HT blocks K+ channels on the sensory neuron's presynaptic terminal membrane
      • Prolongs the presynaptic AP (K+ can't exit the cell to reestablish membrane potential)
      • More Ca++ enters the sensory neuron's presynaptic terminal
      • PrULongs presynaptic release of neurotransmitter
      • Increases excitation of the motor neuron
  • Conditioning in Aplysia
    • Requires correlation of the CS (innocuos stimulus) and UCS (noxious stimulus). If UCS serotonin arrives immediately following a CS-elicited action potential, there is a synergy in the effect on the K+ gates. An even greater potentiation of Ca++ influx and neurotransmitter release occurs.
• Neuronal Learning in the Mammalian Hippocampus: Long-Term Potentiation
  • What is LTP?
    • Puts neuron in a 'potentiated' state
    • cellular basis of learning in mammals
    • if sensitizing stimulus is repeated, sensory neuron produces proteins => LTP
  • Where does LTP occur?
    • First observed in hippocampal neurons, but also occurs in cerebral cortex, amygdala, cerebellum
    • there are NMDA receptors in the hippocampus?
    • "priming" = depolarization post synaptic membrane
  • What neurotransmitter mediates LTP?
    • Glutamate (excitatory amino acid)
    • Ionotropic Glutamate Receptors are classified as:
      • NMDA receptors - Ca++ channel, normally 'plugged' by a Mg++ ion.
      • Non-NMDA receptors - Na++ channel
    • LTP involves both types of glutamate receptor
  • What are the cellular mechanisms underlying LTP?
  • What happens physiologically during LTP? May be more than one mechanism
    • Could be:
      • Increase sensitivity of postsynaptic receptors (illustrated above).
      • Increase number of postsynaptic receptors
      • Increased release of neurotransmitter (via feedback system).
      • Sprouting of new presynaptic terminals
      • Physical changes in postsynaptic structures (increase thickness of dendrites).
    • How could POSTSYNAPTIC enzymes cause #2 & #3? Nitric Oxide (NO). NO is a gas that diffuses over a short distance and can enhance production of presynaptic enzymes (ie. soluble guanylyl cyclase).
  • LTP and Behavior
    • If LTP is a mechanism of LTM, then does blocking NMDA receptors block long-term memory formation? YES
      • Ex. NMDA antagonist can eliminate conditioned fear response in rats
      • Ex. NMDA antagonist can shorten critical period
      • Ex. Old vs. young animals; leaky Ca++ channels => same amount of Ca++ doesn't have the same effect
• The Biochemistry of Learning & Memory
  • The Influence of Protein Synthesis on Learning & Memory
    • Inhibiting protein synthesis inhibits STM->LTM
    • The more severe the protein synthesis inhibition, the more profound the effect on learning.
    • Why? Learning involves persistent changes to the nervous system
  • Acetylcholine Synapses & Memory
    • Alzeheimer's disease: memory deficit correlates to loss of ACh
    • Scopolamine (ACh antagonist) mimics memory impairment of senility
    • Do Ach dietary precursors help memory? NO. (Choline & lecithin)
    • Do drugs that increase ACh neurotransmission help memory? YES. (Physostigmine) Bad side effects