model system: sea hare (Aplysia californica) behavior: the gill & siphon withdrawal reflex even more cell biology: learning & memory summary

PART 4: BEHAVIORAL PLASTICITY#21: LEARNING & MEMORY of a SIMPLE

REFLEX in APLYSIA II

model system: sea hare (Aplysia californica) behavior: the gill & siphon withdrawal reflex even more cell biology: learning & memory summary

PART 4: BEHAVIORAL PLASTICITY#21: LEARNING & MEMORY of a SIMPLE

REFLEX in APLYSIA II

mechanistic analysis of classical conditioning convergence of CS & US in sensory neuron adenylyl cyclase (AC) = coincidence detector? sensitization:

Ca++ channels closed Ca++ not bound to calmodulin calmodulin not bound to AC some cAMP ...

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning convergence of CS & US in sensory neuron adenylyl cyclase (AC) = coincidence detector? associative learning:

Ca++ channels open Ca++ bound to calmodulin calmodulin bound to AC lots of cAMP ...

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

glutamate, excitatory transmitter activates N-methyl-D-aspartate (NMDA) receptor

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

glutamate, excitatory transmitter activates N-methyl-D-aspartate (NMDA) receptor no signal...

NMDA channel closed no Ca++ enters cell

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

glutamate, excitatory transmitter activates N-methyl-D-aspartate (NMDA) receptor signal...

glutamate binds to receptor postsynaptic membrane

depolarizes postsynaptic neuron fires test this model?

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

differential conditioning

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

differential conditioning

aminophosphonovalerate (APV) block of NMDA receptor…

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

differential conditioning block NMDA receptor with APV during training

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

differential conditioning block NMDA receptor with APV during training associative synaptic facilitation

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

differential conditioning block NMDA receptor with APV during training associative synaptic facilitation NMDA receptor necessary

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

differential conditioning same result during training if

postsynaptic neuron: hyperpolarized Ca++ blocked

presynaptic neuron: PKA blocked Ca++

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning postsynaptic factors

implication that the postsynaptic neuron communicates with the presynaptic neuron

retrograde (backward) signaling evidence (not shown) – associative facilitation

mechanism in postsynaptic neuron changes signaling properties in the presynaptic neuron

neurons communicate in both directions but... what is the signal?

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning revised model

2 sites of CS-US coincidence presynaptic AC

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning revised model

2 sites of CS-US coincidence presynaptic AC postsynaptic

NMDA receptorgated channels

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of classical conditioning revised model

2 sites of CS-US coincidence presynaptic AC postsynaptic

NMDA receptorgated channels

retrograde signal(hypothetical)

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons terminology:

long-term memory (LTM) behavioral measure long-term facilitation (LTF) physiological measure

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

distributed sensitization training

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

distributed sensitization training: siphon withdrawal

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

distributed sensitization training siphon withdrawal sensory EPSPs

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

distributed sensitization training siphon withdrawal sensory EPSPs S-current

(data not given)

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

distributed sensitization training siphon withdrawal sensory EPSPs S-current serotonin-induced

presynaptic transmitter release (data not given)

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

distributed sensitization training siphon withdrawal sensory EPSPs S-current serotonin-induced

presynaptic transmitter release (data not given)

presynaptic neuronal plasticity

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

distributed sensitization training serotonin substitutes for tail shock @ sensory

cell body LTF terminal STF

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

distributed sensitization training serotonin substitutes for tail shock @ sensory

cell body LTF terminal STF

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

serotonin induces LTF

intracellular signal protein synthesis (?) neural plasticity (?)

STF locally @ synapse

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

protein synthesis (?) transcription translation transport synapses

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

protein synthesis inhibited by blockers also block LTF

during serotonin application only not before or after... narrow temporal window

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

protein synthesis inhibited by blockers also block LTF

during serotonin application only not before or after... narrow temporal window

no block of STF

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term synaptic facilitation in sensory neurons

protein synthesis inhibited by blockers also block LTF

during serotonin application only not before or after... narrow temporal window

no block of STF ... and does block LTM (behavior) protein synthesis necessary for LTM

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term sensitization / serotonin treatments

molecular changes in sensory neurons: persistent phosphorylation of existing proteins synthesis of new proteins growth of sensory neurons... neural plasticity

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term sensitization / serotonin treatments

molecular changes in sensory neurons: growth of sensory neurons... neural plasticity

visual examination axonal processes,

branching, varicosities

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term sensitization / serotonin treatments

molecular changes in sensory neurons: growth of sensory neurons... neural plasticity

visual examination axonal processes,

branching, varicosities

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term sensitization / serotonin treatments

molecular changes in sensory neurons: growth of sensory neurons... neural plasticity

model for synaptic restructuring / plasticity varicosities terminal active zones opposite for habituation

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory long-term sensitization / serotonin treatments

molecular changes in sensory neurons: growth of sensory neurons... neural plasticity

model for synaptic restructuring / plasticity varicosities terminal active zones

long-term increase in synaptic transmission what are the molecular mechanisms?

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory molecular induction of LTF in sensory neurons

cAMP pathway implicated: cAMP injection ... S-current PKA inhibitors ... block serotonin-induced LTF serotonin application ... PKA catalytic subunit

cytoplasmic nuclear activity of genes:

immediate early (IEG), transcription factors late-responsive, leave nucleus

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory molecular induction of LTF in sensory neurons

cAMP pathway implicated: cAMP response elements (CREs) on DNA CRE binding protein (CREB) phosphorylated by PKA...

CREBs IEGs IEGs late-responsive genes

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory molecular induction of LTF in sensory neurons

single training event some PKA, STF distributed training more PKA... nucleus, LTF

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory molecular induction of LTF in sensory neurons

competition studies using injected CRE sequences block CREB binding & LTF

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory molecular induction of LTF in sensory neurons

competition studies using injected CRE sequences block CREB binding & LTF

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory molecular induction of LTF in sensory neurons

competition studies using injected CRE sequences block CREB binding & LTF

enhanced CREB + 1 serotonin application LTF structural enhancement

CREB essential for LTF & LTM similar findings in Drosophila (next chapter)

CELL BIOLOGY OF LEARNING & MEMORY

mechanistic analysis of long-term memory LTF molecular model

what proteins? how do they work? other 2nd messenger

cascades? homology (flies, mice)

CELL BIOLOGY OF LEARNING & MEMORY

middle-term memory... read the section on your own

CELL BIOLOGY OF LEARNING & MEMORY

defensive withdrawal reflex after stimulation (CS) of siphon, mantle, gill

shows non-associative learning properties habituation, dishabituation, sensitization

sensitization: reflex with preceding tail shock associative learning

reflex (CS) + paired shock (US) differential conditioning = CS1+ + US, CS2–

distributed training long-term memory

SUMMARY

tail shock sensitization interneuron serotonin release sensory neuron K current flow (out of cell) spike broadening synaptic facilitation cAMP cascade mediated sensory neuron transmitter release

SUMMARY

classical conditioning interneuron serotonin release sensory neuron tail shock US responses augmented by

concurrent CS signal... activity-dependent presynaptic facilitation postsynaptic process, NMDA receptor in motor

neuron

SUMMARY

long-term memory dispersed training protein synthesis-dependent cAMP & CREB IEGs IEGs late-response genes proteins neuron terminals neuronal plasticity

SUMMARY