PART 4: BEHAVIORAL PLASTICITY

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PART 4 BEHAVIORAL PLASTICITY 20 LEARNING
MEMORY of a SIMPLE REFLEX in APLYSIA I

• model system sea hare (Aplysia californica)
• behavior the gill siphon withdrawal reflex
• cell biology learning memory
• summary

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PART 4 BEHAVIORAL PLASTICITY 20 LEARNING
MEMORY of a SIMPLE REFLEX in APLYSIA I

• model system sea hare (Aplysia californica)
• behavior the gill siphon withdrawal reflex
• cell biology learning memory
• summary

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SEA HARE ( Aplysia californica)

• slow moving gastropod mollusk
• phylum Mollusca
• order tectibranchia
• subclass Opisthobranchia
• genus Aplysia, about 35 species
• A. californica 15-30 cm, south Pacific waters
• few ( 20K) neurons, some very large
  identifiable
• ? can associate neural function with behavior
• circuitry, cell molecular biology of learning

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SEA HARE ( Aplysia californica)

• gill siphon withdrawal reflex
• top view of A. californica
• tactile stimuli ? gill siphon withdrawn under
  mantle
• covered with parapodium
• reliable behavior
• gt 30 yrs of study
• neural mechanisms
• of learning

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THE GILL SIPHON WITHDRAWL REFLEX

• we will focus on 2 main ideas in this chapter
• non-associative vs associative learning
• memory phases

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THE GILL SIPHON WITHDRAWL REFLEX

• in very general terms, what can animals learn?
• a single stimulus
• temporal relationships among stimuli
• influence of own behavior on 2
• different types of learning
• non-associative learning ? 1 only
• associative learning
• Pavlovian or classical ? 1 2
• operant or instrumental ? 1, 2 3

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THE GILL SIPHON WITHDRAWL REFLEX

• study using Aplysia restrained in aquarium
• tactile stimulation to siphon ? gill retraction
• repeat at 90s interval ? habituation
• electric shock stimulation to tail (or neck)
• gill retraction restored
• ? dishabituation

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THE GILL SIPHON WITHDRAWL REFLEX

• study using Aplysia restrained in aquarium
• tactile stimulation to siphon ? gill retraction
• repeat at 90s interval ? habituation
• electric shock stimulation to tail (or neck)
• gill retraction restored ? dishabituation
• electric shock stimulation to tail in naive
  animals
• gill retraction enhanced ? sensitization
• memory fairly short for all three types (min or
  hrs)
• long-term forms can also be generated

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THE GILL SIPHON WITHDRAWL REFLEX

• associative learning classical or Pavlovian
• US tail shock
• UR rigorous siphon withdrawal
• CS siphon stimulus

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THE GILL SIPHON WITHDRAWL REFLEX

• associative learning classical or Pavlovian
• US tail shock
• UR rigorous siphon withdrawal
• CS siphon stimulus
• training US CS
• test CR rigorous siphon withdrawal

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THE GILL SIPHON WITHDRAWL REFLEX

• associative learning classical or Pavlovian
• test with CS alone after training with
• US only ? sensitization control
• US CS unpaired stimulus control
• US CS paired classical conditioned
• learn siphon stimulus
• predicts tail shock

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THE GILL SIPHON WITHDRAWL REFLEX

• associative learning differential classical
• US tail shock
• UR rigorous siphon withdrawal
• CS1 siphon (or mantle stimulation) paired
• CS2 mantle (or siphon stimulation) unpaired

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THE GILL SIPHON WITHDRAWL REFLEX

• associative learning differential classical
• US tail shock
• UR rigorous siphon withdrawal
• CS1 siphon (or mantle stimulation) paired
• CS2 mantle (or siphon stimulation) unpaired
• training US CS1 paired,
• US CS2 unpaired
• test CR rigorous siphon
• withdrawal

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THE GILL SIPHON WITHDRAWL REFLEX

• associative learning differential classical
• test with CS1 or CS2 alone after training with
• CS1 siphon (or mantle stimulation) paired
• CS2 mantle (or siphon stim.) unpaired
• learn that CS predicts tail shock

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THE GILL SIPHON WITHDRAWL REFLEX

• associative learning interstimulus interval
• CS must precede US in training
• 0.5 s in A. californica
• no learning with backward conditioning

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THE GILL SIPHON WITHDRAWL REFLEX

• long-term memory
• short-term memory ? minutes / hours
• long-term memory ? days / weeks
• distributed (spaced) vs massed training is the key

SPACED
MEMORY
MASSED
TIME
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THE GILL SIPHON WITHDRAWL REFLEX

• long-term memory in habituation
• train 4 days (T1-4)
• test 1 day (R1), 1 wk (R2), 3 wks (R3)

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THE GILL SIPHON WITHDRAWL REFLEX

• long-term memory in habituation
• train 4 days (T1-4)
• test 1 day (R1), 1 wk (R2), 3 wks (R3)

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THE GILL SIPHON WITHDRAWL REFLEX

• long-term memory in sensitization
• train 4 days (T1-4)
• test 1 day (R1), 1 wk (R2), 3 wks (R3)

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THE GILL SIPHON WITHDRAWL REFLEX

• long-term memory in associative learning
• data not shown

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CELL BIOLOGY OF LEARNING MEMORY

• functional architecture of withdrawal reflexes
• ganglia connectives
• bilaterally symmetrical prs
• abdominal ganglion
• important for reflex
• 1 sensory neurons
• interneurons
• motor neurons

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CELL BIOLOGY OF LEARNING MEMORY

• functional architecture of withdrawal reflexes
• neural circuit of reflex
• 20 sensory neurons ? motor neurons
• interneurons
• excite
• inhibit

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CELL BIOLOGY OF LEARNING MEMORY

• functional architecture of withdrawal reflexes
• neural circuit of reflex
• 20 sensory neurons ? motor neurons
• interneurons
• excite
• inhibit
• focus on
• synapses

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CELL BIOLOGY OF LEARNING MEMORY

• big s for using Aplysia
• direct monitor of synaptic transmission...
• of identified neurons...
• in numerous different preparations...
• to measure behavior

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CELL BIOLOGY OF LEARNING MEMORY

• intact preparation
• expose abdominal ganglion
• gill siphon withdrawal triggered measured
• simultaneous intracellular recordings

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CELL BIOLOGY OF LEARNING MEMORY

• semi-intact preparation
• separate organs with neurons
• reliable recording

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CELL BIOLOGY OF LEARNING MEMORY

• isolated abdominal gangion
• direct access to all neural elements
• mimic tactile stimulation with neural stimulation

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CELL BIOLOGY OF LEARNING MEMORY

• cell culture
• most reduced
• examine properties of single synapses between
  sensory and motor neurons
• reconstruct monosynaptic component of reflex

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of sensitization the
  synapse
• synaptic facilitation
• semi-intact preparation
• electrically stimulate tail
• ? sensory to motor EPSP
• presynaptic mechanism
• ? Ca into neuron
• ? transmitter release
• spike broadening

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of sensitization the
  synapse
• synaptic facilitation
• semi-intact preparation
• serotonin application
• ? sensory to motor EPSP
• serotonin blocker
• prevents ? sensory to motor EPSP (not shown)

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of sensitization
  biophysics
• serotonin ? sensory to motor EPSP
• whole cell current voltage clamp
• single ion channel patch clamp
• serotonin ? outward K-current by...
• prolonged closure of 2 S-current channels
• serotonin-sensitive K current (S current)
• delayed K current
• prevents repolarization of membrane
• leads to spike broadening

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of sensitization molecular

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of sensitization molecular
• synaptic facilitation
• semi-intact preparation
• inject cAMP 2nd messenger
• ? sensory to motor EPSP

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of sensitization molecular
• inject PKA catalytic
• subunit same result
• phosphorylates
• (closes) K-channels
• sensitization model
• incomplete

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of classical conditioning
• presynaptic factors
• similarities with sensitization
• reflex facilitation of siphon withdrawal
• induced by tail shock
• facilitation amplified by
• temporal CS-US pairing
• same (amplified)
• mechanism or not?

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of classical conditioning
• presynaptic factors
• similarities with sensitization
• reflex facilitation of siphon withdrawal
• induced by tail shock
• facilitation amplified by temporal CS-US pairing
• same (amplified)
• mechanism or not?
• test with differential
• conditioning paradigm

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of classical conditioning
• presynaptic factors
• semi-intact preparation
• CS1 siphon (SN)
• CS2 mantle (SN)
• US tail shock

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of classical conditioning
• presynaptic factors
• enhanced facilitation in
• paired training
• ? paired vs unpaired
• ? paired vs US alone
• temporal pairing effect
• activity-dependent presynaptic facilitation

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CELL BIOLOGY OF LEARNING MEMORY

• mechanistic analysis of classical conditioning
• presynaptic factors
• differential synaptic facilitation results
  similar to behavioral experiments

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BREAK