We use a multidisciplinary approach that combines behavioral, morphological, electrophysiological, cell biological and molecular-biological techniques to explain the neural basis of those forms of behavioral plasticity that are due to changes in the motivational state of animals.
In view of the complexity of these questions, we have chosen to ask them in a preparation that has a relatively simple nervous system - the marine mollusc Aplysia californica. The central nervous system of this animal is distributed into several ganglia, each of which consists of a limited number of neurons, many of which are large and easily identifiable as unique individuals. The ability to recognize the same neurons from animal to animal has greatly facilitated the functional characterization of individual cells as sensory neurons, motor neurons and interneurons. This in turn has allowed the reconstruction of neuronal circuits that mediate a variety of behaviors.
Our laboratory has been using the feeding behavior of Aplysia to determine the cellular mechanisms that are responsible for those forms of behavioral plasticity that result from changes in the level of hunger and arousal of the animal. Circuit-level analysis has provided new insights into the organization of neuronal networks into mediating and modulatory systems and led to a new conceptualization of command neurons. Studies of transmitters and modulators involved in the regulation of behavior have resulted in purification and sequencing of several novel neuropeptides and to molecular cloning of the mRNA of these molecules. These neuropeptides have now been localized to specific neurons, and shown to act as cotransmitters. To a large extent our research is now focused on the role that these peptidergic cotransmitters play in optimizing the efficiency of behavior in response to changes in the motivational state of the animal. We are particularly interested in determining:
The relationships between different forms of behavior and the patterns of neuronal activity. The dependence of peptide cotransmitter release on the pattern of neuronal activity. The physiological consequences of the interactions between multiple cotransmitters. The subcellular mechanisms involved in the interaction of multiple transmitters and cotransmitters, with particular emphasis on the identification of second messengers and kinases, as well as proteins phosphorylated by these kinases. We expect that this approach will yield a unified picture in which our understanding of behavioral plasticity will extend all the way from behavior to the molecules involved.
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