Thursday, November 21, 2024
11/21/2024
DESCRIPTION (provided by applicant): The long-term objectives of this proposal are to understand the neural bases for the changes in behavior that accompany changes in an animal's social status. Crayfish are an appropriate model because the differences in the behavior of dominant, subordinate and single (isolated) animals are well described, and the neural circuits that mediate relevant patterns of behavior, such as escape, have been well studied. The Lateral Giant (LG) interneuron in the escape circuit serves as a command neuron for the behavior. LG's excitability can be modulated by serotonin (5HT), but the sign of this modulation depends on the social status of the animal: 5HT facilitates LG's response in social dominant animals and inhibits it in social subordinates. The effect of serotonin in social isolates depends on the manner in which it is applied, whether fast or slow, at higher or lower concentrations, and for shorter or longer periods. These last effects, which are of clear clinical relevance, are hypothesized to result from activation of competing second messenger pathways through separate serotonin receptors, whereas the effects of social status may result from changes in the population of available receptors in the different animals. Accordingly, the first aim of the proposal is to describe the set of serotonin receptors that modulate LG's response by cloning, sequencing and expressing crayfish CNS serotonin receptors. Antibodies to those receptors will then reveal their location, and the discovery of selective agonists and antagonists will enable their different effects to be determined, cAMP mediates one effect of 5HT on LG; other 2nd messengers pathways will be identified and their interactions studied through the use of specific agonists and antagonists that can be either applied extracellularly or injected into the giant neuron. One effect of 5HT, long-term facilitation, is also produced by repeated bouts of sensory nerve stimulation; this pattern of stimulation is also known to evoke 5HT release. Another aim will be to determine whether release of 5HT mediates stimulus-induced long-term facilitation. Finally, the afferents to LG are electrically coupled; the final aim will be to test whether this coupling forms a lateral excitatory network among the afferents to select and amplify phasic inputs to LG. This will be studied with standard electrophyiological techniques.
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