The long term goal of the research described in this application is to understand at the 'channel level' how the activity of identifiable neuronal circuits changes under different behavioral states. In this application we propose to investigate the cellular correlates of behavioral plasticity in the feeding circuit of the leech and the role of serotonin thereon. Serotonergic neurons are crucial for the control and integration of both appetitive and consummatory aspects of feeding. The behavior of hungry, sated or conditioned animals in response to food is uniquely different and can be modulated by the exogenous application of serotonin. The systematic behavioral changes resulting from feeding are a general decline in activity and an aversive reaction to the appetitive stimulus which lasts for months. However, little is known about the underlying cellular mechanisms governing the behavioral transition from hungry to sated or aversively conditioned states. As a working hypothesis, we propose that these changes in behavior reflect measurable """"""""plastic"""""""" changes in the central neurons and the muscles that they innervate. Therefore, we are planning to perform experiments utilizing electrophysiological techniques on identified neurons and muscles in the feeding circuit of semi-intact preparations dissected from four distinct groups of leeches 1) hungry 2) sated 3) chemically depleted and 4) aversively conditioned. Several hypothesis will be tested relating the behavior of these four groups to the electrophysiological characteristics of key peripheral and central sites: 1) that feeding will decrease synaptic transmission between peripheral chemosensors and the serotonergic effector neurons 2) that the serotonergic neurons's excitability will decrease as feeding progresses and 3) that autoregulation of transmitter release as well as interactions between peripheral stretch receptors in the body musculature and the serotonergic neurons play a role in modulating the feedback pathway which controls the circuit's motor output. The systematic study of the mechanisms of modulation of ionic conductances in an organized functional network during a wellcharacterized behavior should bring us a step closer to the understanding of the relationship between channel properties and neuronal plasticity. The results may contribute to our understanding of fundamental principles governing normal and aberrant feeding behavior.
