We have briefly examined the role of learning and memory in behavior.

9.031 Neural Basis of Learning and Memory: Lecture 2a

Non-associative learning: Habituation and Sensitization

[Consider some associative forms of learning.]

Look at some simple forms of non-associative learning - habituation and sensitization

Habituation - Learned suppression of response to a repeated stimulus.

Example - suppressed startle reflex to repeated presentation of a loud sound.

Sensitization (pseudoconditioning) - Enhancement of response to a variety of stimuli following stimulus exposure.

Example - stronger response to mild tactile stimulation after a painful one.

Example - Multiple air puffs delivered alone. Each puff produces an eyeblink. If a tone is then sounded alone, an eyeblink will be produced. Note that the UCS (air) and CS (tone) have never been paired (hence the term pseudoconditioning).

Possibilities?

[consider stimulus generalization, or generalized excitement and actual conditioning to the CS of ‘change of stimulation, or change in stimulus energy’’]

[Why are these non-associative.]

Behaviorally they do not involve forming a new association between a stimulus and response, only modifying the characteristics of an existing stimulus and response.

Non-associative - Repeated exposure to a single type of stimulus enables the organism to learn about the properties of the stimulus.

Associative - Exposure to multiple stimuli, or stimuli and responses enables the organism to learn about the relationship between them.

Both types of learning are dependent on experience and can be long lasting.

Now look at the mechanisms by which learning produces changes in the structure and function of neurons and their connections.

Habituation

Learned suppression of response to a repeated stimulus

Studied in simple forms of behavior - reflexes.
Flexion withdrawal is a protective reflex to painful stimuli.
Size, strength, and duration of contraction is a function of stimulus intensity [hot iron vs warm iron]

Sherrington noted that this and other reflexes habituated with repeated stimulation and suggested a decrease in the effectiveness of synaptic transmission in the motor circuits involved.

Spencer and Thompson examined habituation in cat spinal flexion reflex (limb withdrawal).
Intracellular recordings in the spinal cord determined that habituation produces a decrease in synaptic activity between motor neurons and interneurons.

[fig 38-6 showing flexion withdrawal circuit, pg 588]

Due to the complexity of spinal cord circuitry, the cellular basis of habituation was carried into the study of simpler invertebrate systems.

Study simple forms of learning in an invertebrate model.

Aplysia californica

A marine snail with approximately 20,000 neurons in its central nervous system.

[diagram of Aplysia, fig 65-1, pg 1010]

Defensive reflexes for withdrawal of its tail, siphon, and gill.

Tactile stimulation of the siphon produces siphon and gill withdrawal.
Tactile stimulation of the tail produces tail withdrawal.

Repeated stimulation of these reflexes produces habituation.

[These responses can also be sensitized and classically conditioned.]

Gill withdrawal

Stimulation of the siphon activates sensory neurons which drives interneurons and motor neurons causing gill withdrawal.

repeated stimulation of the siphon produces progressively weaker inputs from the sensory neurons.
input from interneurons to motor neurons is also weaker.
weaker motor neuron activity produces weaker withdrawal response.

[Note how this fits into an earlier definition of learning. It is an adaptive change in behavior resulting from experience. It is predictive and long-lasting. It uses modification of innate behavior.]

Mechanisms

Much of the habituation effect can be ascribed to modification of the presynaptic terminal.

reduced Ca++ influx due to inactivation of presynaptic Ca++ channels results in reduced transmitter release.
decreased availability of vesicles for release.
the effects from sensory neurons to motor and interneurons lasts for several minutes following a single session of 10 simulations.
changes lasting weeks are produced in the connections from interneurons to motor neurons after repeated sessions.
these long-lasting changes can involve the structural rearrangement of connections - a reduction in the number of synaptic connections onto a motor neuron.

[why should these changes be presynaptic? look at the model.]

[is the learning a property of the stimulus or the response? Enhanced response to simuli or a selective filtering of a stimulus. Introduces the notion of selectivity in synaptic modification - one active set of connections is modified while others are not. Related concepts are cooperativity, and associativity]

Sensitization

Enhancement of response to a variety of stimuli following stimulus exposure.
Both short and long term components.

A single aversive stimulus to the tail (shock), modifies connections in the gill-withdrawal reflex circuit.

Single trials produce short-term sensitization (minutes in duration). Repeated sessions produce longer lasting effects (weeks)

[fig 65-4, pg 1014]

Facilitation of connections of sensory neurons onto interneurons and motor neurons through interneurons which enhance transmitter release. Note that this is heterosynaptic but involves the same connections as in habituation. Compare with the depression in habituation.

[fig 65-3, pg1013]

Serotonin -> G protein -> increased adenylyl cyclase (ATP/cAMP) -> increased cAMP -> activate cAMP PK ->phosphorylation of K+ channel -> reduced K+ current -> broadened action potentials -> increased Ca++ influx -> increased transmitter release
Serotonin->cAMP PK/PKC -> increased mobilization of transmitter to active zone

Long-term changes effect the same synapses but also involve gene-activation and protein synthesis which may result in structural changes or the addition of new proteins which alter normal levels of cAMP and thus change baseline transmission.

[fig 65-6, pg 1016]

Additional Reading:

Bailey, Chen, "Morphological basis of long-term habituation and sensitization in Aplysia", Science 220:91-93, 1983.

Castellucci, Carew, Kandel, "Cellular analysis of long-term habituation of the gill-withdrawal reflex of Aplysia californica" Science 202:1306-1308, 1978.

Greenberg, Castellucci, Bayley, Schwartz, "A molecular mechanism for long-term sensitization in Aplysia" Nature 329:62-65, 1987.

Spencer, Thompson, Neilson, "Response decrement of the flexion reflex in the acute spinal cat and transient restoration by strong stimuli" J.Neurophys. 29:221-239, 1966.