The overall goal of the proposed research is to investigate a fundamental problem in neuroscience--the physiological basis of learning and memory. The proposed studies will focus on the elucidation of the mechanisms underlying sensitization, a simple form of non-associative learning, the memory for which has both short- (minutes) and long- (days) term forms. The first aim is to investigate biophysical correlates of long-term sensitization and the interactions between long-term sensitization and the processes that underlie the synaptic profile. Particular attention will be paid to the "synaptic profile," which is defined as the monosynaptic PSPs produced in a motor neuron by a brief burst of activity in a presynaptic sensory neuron. Such a burst of activity mimics the response of the system to behaviorally relevant stimuli. Moreover, the synaptic profile simultaneously engages several processes that regulate synaptic transmission and plasticity. Thus, investigating the synaptic profile has provided new insights to the mechanisms of synaptic plasticity. These insights were not revealed previously by studies that used the more traditional approach of investigating synaptic responses to a single presynaptic spike. The specific objectives of the first aim are: 1) Characterize additional correlates of long-term sensitization, such as changes in the synaptic profile and presynaptic spike waveform and cellular changes following one vs. four days of training; 2) Investigate the role of the growth factor TGF-beta in the expression of long-term sensitization; and 3) Examine the contribution of persistently active kinases to the expression of long-term sensitization. The second aim is to investigate the role of the synaptic vesicle protein synapsin and its phosphorylation in short and long-term synaptic plasticity at sensorimotor synapses. The specific objectives of the second aim are: 1) Examine the functional role of synapsin and its phosphorylation in short-term homo- and hetero-synaptic plasticity; 2) Investigate the regulation of the subcellular localization of synapsin by 5-HT; and 3) Investigate the role of synapsin in long-term plasticity. The third aim is designed to examine possible contribution of postsynaptic processes to the synaptic profile and its modulation. The specific objectives of the third aim are: 1) Investigate the contribution of receptor desensitization to the synaptic profile; 2) Determine the ways in which heterosynaptic modulation modifies the processes that underlie the synaptic profile; and 3) Determine the role of desensitization in the synaptic facilitation underlying long-term sensitization.