Chapter Thirteen The Biology of Learning and Memory

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Chapter ThirteenThe Biology of Learning and
Memory
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Chapter ThirteenThe Biology of Learning and
Memory
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Localized Representations of Memory
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• Pavlovs classical conditioning
• unconditioned stimulus (meat) automatically
  elicits an unconditioned response (dog salivates)
• conditioned stimulus (metronome) initially
  elicits no response
• conditioned response (dog salivates to metronome)
  is learned with repeated pairings of metronome
  with meat
• but in some cases the learned behavior is not the
  same, e.g., if rat experiences light paired with
  shock, the shock elicits jumping but the CS
  elicits freezing

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Localized Representations of Memory cont.
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• Operant Conditioning an individuals response is
  followed by a reinforcement or punishment
• reinforcement event that increases the future
  probability of the response
• e.g. given froot loops for a correct response, a
  rat learns to return to the same arm of maze
• punishment event that suppresses the frequency
  of the response
• e.g. given a shock for the wrong response, a rat
  learns to avoid arm of maze

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Figure 13.1
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• Figure 13.1 Procedures for classical conditioning
  and operant conditioning. (a) In classical
  conditioning two stimuli (CS and UCS) are
  presented at certain times regardless of what the
  learner does. (b) In operant conditioning the
  learners behavior controls the presentation of
  reinforcement or punishment.

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Localized Representations of Memory cont.
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• Lashley searched for the engram, the physical
  representation of what has been learned (e.g.,
  connecting two brain areas through long term
  synaptic processes)
• he trained rats on mazes and brightness
  discrimination tasks and made cuts between two
  brain areas or removed part of the brain
• none of the deep cuts disrupted maze performance
• maze performance was only decreased when large
  amounts of brain were removed
• learning and memory does not depend on a single
  cortical area

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Localized Representations of Memory cont.
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• Lashley proposed two principles
• equipotentiality all parts of the cortex
  contribute equally to complex behaviors like
  learning
• mass action the cortex works as a whole, the
  more cortex the better
• incorrectly assumed that all kinds of memory were
  physiologically the same and that the cortical
  area was the best place to search for an engram

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Modern Search for the Engram
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• Thompson et al in a classical conditioning task,
  they paired tone with puff of air until rabbit
  blinked at tone
• found changes in cells in the lateral
  interpositus nucleus (LIP) of cerebellum
• when LIP was cooled or drugged the rabbit did not
  learn and later when effects wore off rabbit
  learned at same rate as new rabbits
• LIP had to be active to learn

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Modern Search for the Engram cont.
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• Thompson et al then suppressed activity in red
  nucleus (mid-brain motor area that receives input
  from cerebellum)
• rabbits showed no response during training
• when effects wore off rabbits showed strong
  learned response to CS
• thus, red nucleus necessary for performance, not
  learning, of response

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Modern Search for the Engram cont.
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• Thompson found that
• A. the engram is equipotential across multiple
  areas
• B. the engram is in the red nucleus
• C. the engram is in the cerebellum
• D. the engram is an oversimplified concept

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Figure 13.4
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• Figure 13.4 Localization of an engram. Rabbits
  were trained on classical conditioning of an
  eyelid response. Temporary suppression of
  activity in the lateral interpositus nucleus of a
  rabbit blocked all indications of learning. After
  the suppression wore off, the rabbits learned as
  slowly as rabbits with no previous training.
  Temporary suppression of activity in the red
  nucleus blocked the response during he period of
  suppression, but the learned response appeared as
  soon as the red nucleus recovered from the
  suppression. (Source Bases on the experiments of
  Clark Lavond, 1993, and Krupa, Thompson,
  Thompson, 1993.)

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Modern Search for the Engram cont.
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• Probably same in humans
• classical conditioning of eye blink produced
  activity in cerebellum, red nucleus and other
  areas
• people with damage to cerebellum are impaired at
  eye-blink task

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Hebb Short and Long-Term Memory
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• Short-term events that have just occurred
• limited capacity, around 7 unrelated items
• if forgotten is lost forever
• Long-term events from previous times
• not lost, are recoverable
• Consolidation
• memories that stay in short-term memory long
  enough are formed into long-term memory

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Consolidation of Long-Term Memory
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• Research used ECS to disrupt memory, looking for
  short-and long term memory threshold
• but, shock to head disrupted both short-term and
  long-term memories
• also, some disrupted memories could be recovered
  after reminder of event
• Human studies weaken the distinction between
  short- and long term memory
• we can recall events more than a few hours, or
  days, old but nevertheless will be forgotten in
  near future

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Consolidation of Long-Term Memory cont.
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• Protein phosphatase 1 interferes with retention
  by inactivating genes that promote learning
• we easily forget single experience
• PP1 accumulates during massed practice and
  declines during distributed practice
• Consolidation is gradual and we recall older
  memories easier
• older people showed most MRI activity to
  celebrities in the 1990s and least to celebrities
  in the 1940s
• people showed more temporal lobe activity to
  places visited in last 2 years than those visited
  in last 7 years

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Consolidation of Long-Term Memory cont.
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• What is the best study method? Why?
• A. massed practice
• B. studying at intervals
• C. studying for short periods
• D. studying for long periods
• Why?

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Consolidation of Long-Term Memory cont.
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• Meaningful and emotional experiences enhance
  memory consolidation, e.g, receiving award or
  being in car wreck
• increases secretion of cortisol and epinephrine
• epinephrine stimulates vagus nerve which excites
  cells in brain stem to activate the amygdala

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Consolidation of Long-Term Memory cont.
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• Direct injections of cortisol or epinephrine
  enhance storage and consolidation
• but prolonged stress results in more cortisol and
  memory is impaired
• THE U SHAPED CURVE
• After damage to amygdala, emotional arousal does
  not enhance memory storage
• patients didnt remember taboo words better
• FLASHBULB MEMORY

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Baddeley Hitch Working Memory
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• Working memory we store information while
  working with it or attending to it
• visuospatial sketchpad stores visual information
  
• phonological loop stores auditory information
  independent of visual memory
• central executive directs attention toward one
  stimulus or another

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Baddeley Hitch Working Memory cont.
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• Prefrontal cortex stores working memories
• shows high activity during delayed response tasks
  performed by humans and other mammals
• also in tasks requiring different responses to
  signals given only after a delay
• the stronger the activation in this area the
  better the performance

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Hippocampus and Amnesia
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• H.M. had hippocampus removed which resulted in
• moderate retrograde amnesia for events 1-3 years
  before operation
• could not remember events after the operation
• could not learn to find way to bathroom in
  hospital
• could not remember telling story a few minutes
  later
• could define common words but not infrequently
  used words
• can learn new facts slowly, e.g., floor plan of
  home over many years

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Hippocampus and Amnesia
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• H.M. cont.
• declarative memory deficit cant state memory in
  words
• procedural memory intact can develop motor
  skills
• can read words written backwards
• can draw something seen in mirror
• explicit memory deficit cant recall some
  memories in response to question, e.g., who are
  characters in novel?
• implicit memory better experience influences
  behavior even if not remembered, e.g., always
  chose person who was friendly to him

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Function of the Hippocampus
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• Some support for critical role in declarative,
  explicit memory
• true for H.M.
• monkeys with damage are impaired in delayed
  matching (or non-matching) to sample task
• but performs well if task always uses same
  objects
• rats with damage have difficulty in learning
  correct temporal sequence for reward

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Function of the Hippocampus cont.
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• Strong support for role in spatial memory
• route questions to London taxi drivers activated
  hippocampus more than non-spatial questions
• size of hippocampus related to length of time on
  job
• damage impairs performance on spatial memory
  tasks, e.g., finding your way from one place to
  another
• rats with damage here often enter correct alleys
  repeatedly and forget where platform is under
  water
• correlation between hippocampus size and spatial
  memory in jay birds

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Function of the Hippocampus cont.
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• Some support for role in configural memory where
  meaning depends on what is paired with stimulus
• e.g. you learn that A or B means food and then A
  and B together means no food
• but, damage impairs configural learning as well
  as memory on nonconfigural tasks
• current hypothesis is that hippocampus quickly
  records stimuli that occur together only once and
  cortex detects repeated combinations
• may bind pieces of experience in recall

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Function of the Hippocampus cont.
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• Some support for role in the release of adrenal
  hormones
• damage elevates adrenal release at same time it
  impairs memory
• if drugs are used to block surge of hormones,
  spatial memory returns to normal
• if so, why does damage affect memory at all

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Korsakoffs Syndrome
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• Brain damage caused by long-term thiamin (B1)
  deficiency
• cannot metabolize glucose (fuel)
• leads to shrinkage of neurons throughout brain
• especially in mamillary bodies in hippocampus and
  thalamus axons to prefrontal cortex
• apathy,confusion, amnesia
• better implicit than explicit memory
• difficulty ordering past events
• confabulates, i.e., remembers guesses as true
  memories

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Alzheimers Disease
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• Severe memory loss associated with aging
• Strikes 50 of those over 85
• Better procedural than declarative memory, e.g.,
  can acquire new skills but doesnt remember
  learning
• Genetic components
• person with Downs syndrome (3 copies of
  chromosome 21) always acquire Alzheimers in
  middle age
• genes on chromosome 14 and 1 related to early
  onset
• genes on chromosome 10 and 19 related to late
  onset

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Alzheimers Disease cont.
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• Environmental component
• half of all cases have no known relatives with
  disease
• Yoruba people of Nigeria have high-risk genes but
  lower incidence, maybe due to low-calorie, low
  fat, low salt diet
• Brain proteins fold abnormally, clump together
  and interfere with normal neuronal activity
• amyloid protein produces Aß42 plaques between
  neurons
• tau protein produce tangles in cell bodies
• apolipoprotein E causes cell loss and prevents
  removal of Aß42

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Alzheimers Disease cont.
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• Treatment
• elevated levels of glucose and insulin enhance
  memory
• drugs that increase acetylcholine activity
  increase some aspects of memory
• diet rich in antioxidants
• block Aß42 production, inoculate with small
  amounts of Aß42

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Aplysia and the Study of Learning
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• D.O. Hebb proposed that when an axon successfully
  stimulates a cell it will be even more successful
  in the future
• Aplysia, a marine invertebrate, is a popular
  experimental animal
• has few neurons and it is easy to study behavior
  change as a result of neuronal activity
• touch results in the withdrawal of the siphon,
  mantle or gill
• often study the withdrawal response and learning

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Aplysia and the Study of Learning cont
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• Habituation
• after repeated stimulation of gills the sensory
  neuron no longer increases action potentials to
  stimulate motor neuron
• Sensitization
• intense stimulus anywhere on skin excites
  facilitating neuron to release serotonin onto
  presynaptic terminals of sensory and excitatory
  neurons, prolonging neurotransmitter release
• Thus, changes in synaptic activity produces
  behavioral plasticity, i.e., change due to
  learning

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Figure 13.19
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• Figure 13.19 Sensitization of the withdrawal
  response in Aplysia. Stimulation of the sensory
  neuron ordinarily excites the motor neuron,
  partly by a direct path and partly by stimulation
  of an excitatory interneuron. Stimulation of a
  facilitating interneuron releases serotonin to
  the presynaptic receptors on the sensory neuron,
  blocking potassium channels and thereby
  prolonging the release of neurotransmitter. This
  effect can be long-lasting. (Source After Kandel
  Schwartz, 1982.)

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Long-term Potentiation (LTP) and Depression (LTD)
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• LTP a burst of stimulation from axons, e.g., 100
  excitations per second for 1-4 seconds onto
  dendrites results in potentiated synapses for
  minutes, days or weeks
• specificity only active synapses become
  strengthened
• cooperativity nearly simultaneous stimulation by
  two or more axons results in LTP
• associativity pairing a weak input with a strong
  input enhances later response to the weak input
• LTD prolonged decrease in response to a synaptic
  input where two or more axons have been active
  together at 1-4 times per second

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Biochemical Mechanisms of LTP in Hippocampus
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• AMPA and NMDA receptors are involved in LTP
• glutamate receptors that open channels in
  postsynaptic neurons to let in one or more kinds
  of ions (ionotropic)
• AMPA receptors glutamate opens sodium channels
• similar to what we have studied

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Biochemical Mechanisms of LTP in Hippocampus cont.
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• NMDA receptors normally blocked by magnesium but
  responds to glutamate when depolarized by AMPA
  receptors
• calcium enters and activates protein CaMKII,
  which is necessary for LTP, and sets several
  processes in motion
• structure of AMPA receptors change, becoming more
  responsive to glutamate
• some NMDA receptors change to AMPA receptors and
  increase their responsiveness to glutamate
• dendrites may build more AMPA receptors and make
  more branches
• Once established, LTP no longer depends on NMDA
  synapses

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Figure 13.21
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• Figure 13.21 The AMPA and NMDA receptors during
  LTP. If one or (better) more AMPA receptors have
  been repeatedly stimulated, enough sodium enters
  to largely depolarize the dendrites membrane.
  Doing so displaces the magnesium ions and
  therefore enables glutamate to stimulate the NMDA
  receptor. Both sodium and calcium enter through
  the NMDA receptors channel.

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Biochemical Mechanisms of LTP in Hippocampus cont.
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• Presynaptic changes
• stimulation of the postsynaptic cell releases a
  retrograde transmitter that feeds back to
  presynaptic cell
• increases presynaptic release of neurotransmitter
  and production of GAP-43, facilitating growth of
  axons
• Consolidation of LTP
• following training, LTP seen in hippocampus
  quickly and in cerebral cortex 90-180 minutes
  later
• drugs that block NMDA receptors within 2 weeks of
  training also block consolidation of long-term
  memory
• but, other studies found blocking NMDA for first
  week prolonged LTP and increased dendritic
  branching

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LTP and Behavior
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• Neurons change early in training, a preliminary
  step before behavioral change
• Research with mice
• abnormal NMDA receptors impair learning
• more than normal NMDA receptors enhances learning
• drugs that block LTP block learning while drugs
  that facilitate LTP facilitate learning
• a lack of AMPA receptors creates deficits in LTP
  and memory
• over production of GAP-43 enhances learning and
  problem solving

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LTP and Behavior cont.
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• Can drugs improve your memory?
• gingko biloba sometimes produces small benefits
  in Alzheimers patients or others with
  circulatory problems
• no research on combination of memory-boosting
  supplements