Aplysia – Learning and Memory

Activity dependent changes in synaptic transmission that can alter the normal circuitry and thus behavioral response

Mechanisms underlying learning does not require formation of new neurons, but strengthening connections between existing neurons

Neurons that fire together wire together -Proposed synaptic plasticity as a theoretical mechanism for learning and memory

Circuit Function Both Pre-and Post synaptic locations

-Seconds to minutes 1. Post-translational modification of existing proteins

-Hours/Days/Years 1. Changes in Gene expression 2. Protein Synthesis 3. Growth of new synapses

1.

Development 2. Learning 3. Memory 4. Motor Control

1. NMDA Receptor Activation 2.

Protein Kinase Activation 3. Phosphatase Activation 4. AMPA Receptor Insertion 5. Gene expression and protein synthesis 6.

Growth/Loss of synapses

Huge neurons - over 100 microns in diameter You can stick an electrode in with your hand

1. Habituation 2. Sensitization 3. Classical Conditioning

Presynaptic - Kandelians Postsynaptic - Glanzman

Reductionist! This is a simpler system with a simpler NS

2x10^4 Human has 10^12

Tactile or electrical stimulation of the siphon or mantle elicits withdrawal of the gill & siphon into the mantle cavity

Reflective mechanism - not associating a stimulus with anything Poke in the eye is going to cause you to reflexively avoid that in the future

Habituation - a meaningless stimulus might startle someone the first time (clap) but get less reaction later

A consistent interval within a short period of time

Reduction of a response with repeated presentation of a stimulus

Muscle Fatigue Change in motor neuron response

A touch on the head (not siphon) produces a full response after habituation has occurred

Reduction of synaptic release of NT at some point in the neural network

Keep NS intact, cut away most of body, leave the siphon skin & tail still connected together and to the system -Map the synaptic connectivity

Sensory neuron to interneuron Interneuron to motor neuron to gill **Sensory neuron also goes straight to motor neuron

Sensory neuron to modulatory interneuron Modulatory neuron to interneuon Interneuron to motor neuron to gill **Modulatory interneuron also goes straight to motor neuron

Presynaptic Phenomenon -Depression of NT release between the siphon afferent and the motor neuron **NOT synaptic fatigue, bc that behavior comes back when you re sensitize the animal

Lasts for Minutes -Presynaptic -Reduction in strength of excitatory synapses between sensory neuron and motor neuron -Decrease in number of synaptic vesicles available for release

Generalization of an aversive response elicited by a noxious stimulus to another non-noxious stimuli

Presynaptic -Recruitment of additional synaptic elements that modulate synaptic transmission at sensory neuron-motor neuron synapse -Enhancement of NT release onto motor neurons

Short - Presynaptic Long - Becomes both pre and post synaptic

Glutamate

Serotonin is released presnaptically & acts through adenylyl cyclase to ultimately close K+ channels

1.

Serotonin binds to receptor on sensory neuron 2. Activates adenylyl cyclase 3. ATP to cAMP 4. cAMP activates PKA 5.

PKA closes K+ channels 6. Depolarizes the cell 7. VG Ca2+ channels open 8. Ca2+ comes in 9.

Increase in vesicle release 10. Increases response of a motor neuron to the same stimulus

1. Same steps with serotonin & eventual PKA activity 2. Sustained PKA activity - gets translocated to the nucleus 3. Ultimately binds to TF in nucleus 4.

Activates transcription of genes 5. Some of those are enzymes that keep PKA in activate state 6. Leading to an increase in Ca2+ concentration & bigger post synaptic response

Structural! Number of synapse is increasing as well as the efficacy of those synapses

Change in responsiveness to one stimulus (CS) based on association with another stimulus (US)

US - Shock CS - Lightly touching the siphon Eventually, touching the siphon will lead to a strong withdrawal reflex

Enhanced presynaptic facilitation -Ca2+ channels open bc CS already fired the sensory neuron -Serotonin effect is enhanced bc Ca2+ binds to calmodulin - binds to adenylyl cyclase, etc

Classical Conditioning Sensitization

Coincidence Detectors on the motor neuron

1) LTP 2) Upregulation of AMPA receptor function 3) Stimulation of retrograde signal

1) Late Phase presynaptic facilitation 2) Late-Phase hyperexcitability