HOW ARE MEMORIES STORED

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HOW ARE MEMORIES STORED?
Cellular Biology of Simple Memory Circuits
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To Understand Memory we Must Study Molecular
Mechanisms of Memory Storage

• Lets Start SIMPLE!!!!

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Invertebrates

• Id. nerve cells involved in particular kind of
  learning memory
• Try to figure out what molecular changes w/i
  cells are responsible for learning memory

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Aplysia

• CNS 10 ganglia (2000cells/ganglia)
• Used to examine simple forms of memory
• Gill withdrawal reflex studies used extensively
  to study 3 simple forms of learning..

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Habituation Sensitization Classical Conditioning

• For each type of learning -
• anatomical circuit of neurons has been
  characterized
• cellular, molecular mechanisms that underlie
  have been examined

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Gill Withdrawal Reflex
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Gill Withdrawal Reflex
glut
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Habituation

• Nondeclarative- simple form of learning, learn to
  ignore a benign stimulus not crucial to survival
• Aplysia - stimulate gill repeatedly gill
  withdrawal reflex habituates
• EPSPs in motor neurons weaker so magnitude of
  withdrawal reflex decreased.
• 1 session (10 stimuli) weakening of synaptic
  connection for minutes
• 2nd session - more weak, lasts longer

Synaptic connections undergo plastic changes as a
result of learning. SUCH changes form cellular
basis for STM storage.
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Motor neuron EPSPs
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How is Memory stored in this pre-wired circuit?!
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Strength of Connections
Decreased amount of glutamate released by
sensory neuronthis is transient
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General Principles about Memory Storage

• Connections between neurons can be modified
  serve elementary components of memory storage
• Changing amount of NT released common mechanism
  in creating memory
• Memory storage distributed thru multiple sites
• Nondeclarative memory does NOT depend on
  specialized memory neurons. The memory of
  habituation is EMBEDDED in neural circuit that
  produces the behavior

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LTM - fewer presynaptic terminals
4 days / 40 trials per day habituation Last for
weeks
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MORE PRINCIPLES!!!

• STM involves short term changes in synaptic
  strength, LTM long term changes
• Same synaptic connections participate in storage
  of both STM LTM
• Synapses are plastic in both amt of NT released
  but also in shape structure

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Sensitization

• Increase in reflex magnitude to a stimulus after
  exposure to some other noxious stimulus
• Learns to respond more vigorously to variety of
  other stimuli
• Allows animal to sharpen defensive reflexes in
  preparation for escape
• More complex than habituation

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The Set Up
Enhanced gill w/drawal to a benign
stimulus Following a shock to the tail
Single shock STM (min) 4-5 shocks LTM
(days) gt5 shocks weeks
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• The noxious stim enhances a of same synaptic
  connections that are depressed in habituation
• THUS same set of synaptic connections can be
  modulated in OPPOSITE directions by different
  forms of learning and.
• SAME SET OF CONNECTIONS CAN PARTICIPATE IN
  STORING DIFFERENT MEMORIES

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How Does this Happen?
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ACQUISITION OF AN ASSOCIATION BETWEEN 2 STIMULI
CLASSICAL CONDITIONING - MOST SIMPLE FORM
OF ASSOCIATIVE LEARNING, allows animals to
recognize predictive relationships within their
environment
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IVAN PAVLOV

• Neutral stim (CS) UCS (produces response by
  itself) presented in close temporal proximity CR

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Aplysia Can be Classically Conditioned
Tail shock
modulatory interneuron
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Presynaptic Molecular Changes

• CS (mantle stroke) allows Ca into sensory
  neuron.
• US activates modulatory interneuron that releases
  5-HT. 5-HT activates adenylyl cyclase in
  sensory neuron.
• In presence of elevated Ca, adenylyl cyclase
  churns out more cAMP. Thus, more PKA and more
  PO4 of K channels.MORE NT released.