Habituation and Sensitization in Tritonia

Studies of learning in both vertebrates and invertebrates indicate that individual memories are stored in the brain as distributed sets of cellular and synaptic modifications. Most research in this area has focused on characterizing the detailed mechanisms underlying specific sites of learning-related plasticity, such as presynaptic facilitation at sensory to motor neuron synapses in the marine mollusc Aplysia and long-term potentiation at synapses in the vertebrate hippocampus. However, the fragmented nature of memory storage raises additional issues at a network, rather than synaptic, level. For example, how is the information represented by a given memory organized across the different sites of plasticity encoding it—do different sites store the same information redundantly, or does each encode a unique component of the total acquired information? If different memories overlap in the brain, as seems likely, how do they avoid interfering with one another? Such network-level issues of memory storage have been investigated in the marine mollusc Tritonia diomedea, an organism well suited to both cellular and network studies of learning and memory.

When touched by the tube feet of its highly mobile seastar predators, Tritonia responds with vigorous alternating ventral and dorsal body flexions that propel it away to safety. The neural circuit underlying this response is known in detail and consists of identified afferent neurons, command interneurons, central pattern generator (CPG) interneurons, and efferent flexion neurons. A key advantage for cellular studies of learning is that the neural program underlying the swim behavior can be readily elicited in the isolated brain preparation, where the neurons and synapses storing memory can be easily identified and studied.

Studies of behavioral plasticity in Tritonia have focused on two universal forms of nonassociative learning: habituation and sensitization. Sensitization refers to the increase in responsiveness that follows a single, unexpected, and therefore potentially dangerous stimulus. Habituation refers to the gradual decrease in responsiveness that occurs in response to repetitive innocuous stimuli. In Tritonia, a single swim stimulus produces a period of sensitization, during which test swims have a lower threshold, faster onset latency, and higher cycle number (Frost, Brandon, and Mongeluzi, 1998). On the other hand, repeatedly eliciting the escape swim leads to habituation, characterized by swims with fewer cycles, a higher threshold, and a longer cycle period (Frost, Brown, and Getting, 1996).

Evidence suggests that the multiple, habituation-related behavioral changes are encoded by distributed sites of plasticity in the swim circuit. First, habituation is accompanied by a progressive drop in the number of incoming afferent neuron action potentials per stimulus. In addition, the synaptic connections made by the afferent neurons progressively decrease in strength with repeated stimulation. Bypassing the afferent neurons with repeated intracellular stimulation of the swim-command neurons still results in a progressive decrement of the number of cycles per swim motor program, implicating the involvement of interneuronal sites of plasticity. This is further supported by the finding that habituation produced by stimulating one sensory neuron population also leads to habituation of swims elicited by previously unstimulated sensory populations (Frost et al., 1996).

The memory for sensitization also appears to be encoded by multiple circuit modifications. Sensitizing stimuli produce a long-lasting enhancement of the excitability and synaptic strength of CPG neuron C2. An important effect of this enhancement is to strengthen a positive feedback connection from C2 to the command neurons that drive the swim motor program. Sensitizing stimuli also cause prolonged tonic firing of the CPG's Dorsal Swim Interneurons. These serotonergic cells participate in generating the swim motor program and also appear responsible for the neuromodulatory enhancement of C2 excitability and synaptic strength observed in sensitization (Katz, Getting, and Frost, 1994; Katz and Frost, 1997).

Scientists are just beginning to understand how the information represented by habituation and sensitization is organized in the Tritonia circuitry. After ten stimulus trials animals often display both forms of learning simultaneously—habituation of swim cycle number and sensitization of swim onset latency (Mongeluzi and Frost, 2000). That these two components of the different memories can coexist without conflict suggests that they involve different anatomical loci in the swim circuit. Other swim features modified in sensitization—cycle number and threshold—reverse direction during habituation training, suggesting that the underlying circuit modifications may be located at the same sites for both forms of learning. Studies since the 1990s have sought to determine the behavioral role (information content) of each site of learning-related plasticity.

See also:APLYSIA: MOLECULAR BASIS OF LONG-TERM SENSITIZATION; INVERTEBRATE LEARNING: C. ELEGANS; ORIENTING REFLEX HABITUATION; VESTIBULO-OCULAR REFLEX (VOR) PLASTICITY

Bibliography

Frost, W. N., Brandon, C. L., Mongeluzi, D. L. (1998). Sensitization of the Tritonia escape swim. Neurobiology of Learning and Memory 69, 126-135.

Frost, W. N., Brown, G., Getting, P. A. (1996). Parametric features of habituation of swim cycle number in the marine mollusc Tritonia diomedea. Neurobiology of Learning and Memory 65, 125-134.

Katz, P. S., Frost, W. N. (1997). Removal of spike frequency adaptation via neuromodulation intrinsic to the Tritonia escape swim central pattern generator. Journal of Neuroscience 17, 7,703-7,713.

Katz, P. S., Getting, P. A., Frost, W. N. (1994). Dynamic neuro-modulation of synaptic strength intrinsic to a central pattern generator circuit. Nature 367, 729-731.

Mongeluzi, D. L., Frost, W. N. (2000). Dishabituation of the Tritonia escape swim. Learning and Memory 7, 43-47.

William N.Frost