The ultimate goal of this project is to find the physiological, morphological and biochemical changes responsible for the recovery of neural and behavioral function after a neurological lesion. The results to date suggest that recovery of swimming behavior in the leech is accomplished by strengthening pre-existing synaptic connections secondary to sprouting of the swim-related neurons, possibly of those utilizing or responding to serotonin as their transmitter. In order to interpret these results unambiguously, we must first have a complete neuronal understanding of the swimming behavior. Hence, experiments will be performed both to characterize normal function and to show how function is restored after a lesion. Specifically, we will ask five questions: 1. Do newly discovered interneurons provide a complete explanation of the swimming motor pattern generation? 2. By what neuronal mechanisms does serotonin affect swimming pattern generation? 3. How does swimming relate to other leech behaviors? 4. How does the lesion trigger sprouting? 5. Can sprouting account for the neuronal changes responsible for the behavioral changes? To answer these questions, we must use physiological, anatomical, and pharmacological techniques. To complete the characterization of the swim pattern generator, we will record intracellularly from identified neurons to test the strength of their interconnections and, if necessary, search among the unidentified cells for neurons with pattern generating properties. We will apply serotonin and serotonin inhibitors to the ganglion while recording from pairs of swim-related neurons, to establish the cellular mechanism for the modulatory function of serotonin. We will use a variety of physiological anatomical techniques to find the trigger for neuronal sprouting and to test the importance of sprouting in functional recovery.
