While tremendous progress has been made in elucidating the neural bases of sensory processing and motor pattern generation, far less is known about the mechanismws underlying motor program initiation-the decision-making process that determines whether a particular behavioral act will occur. This topic is of considerable interest, both because decision-making is one of the highest-level functions performed by any nervous system, and because a number of neurological diseases specifically disrupt our ability to initiate behavior. The first Specific Aim will test a set of three hypotheses about how the marine mollusc, Tritonia diomedea, decides whether or not to initiate an escape swim in response to an aversive stimulus. The project aims to identify the circuit mechanisms responsible for the animal's high resting behavioral threshold, and in particular, how sensory input acts to overcome this threshold and initiate a sustained behavioral response. The second Specific Aim will examine the mechanisms underlying one of the most interesting aspects of decision-making-the fact that past experience can strongly influence the likelihood that a particular behavior will be initiated the next time opportunity presents itself. The project will attempt to determine how two forms of nonassociative learning, habituation and sensitization, act on the threshold mechanisms described in Specific Aim 1 to bias decision-making one way versus another. Sensitization training makes Tritonia more likely to swim, while habituation training makes it less likely. The project will also investigate the cellular basis of prepulse inhibition (PPI), a form of behavioral plasticity in which an innocuous pre-stimulus prevents or reduces the behavioral response normally elicited by a strong test stimulus. Deficits in PPI have been suggested to underlie some of the cognitive disturbances in schizophrenia, thus the physiological basis of PPI is of considerable interest. The experiments will test the possibility, suggested by preliminary data, that PPI is mediated by presynaptic inhibition directed onto the first four hierarchical levels of the swim circuit-the very elements that have the most to do with decision-making in Tritonia.
Each aim will employ the combined methodologies of electrophysiology and realistic computer simulations.
