Neuronal circuits produce reliable and consistent functional output throughout life despite constant molecular turnover, developmental growth, and a changing environment. How these networks homeostatically regulate their activity levels to remain within functional bounds has important implications for development, recovery from injury, learning, memory, and pathological conditions such as epilepsy, where regulation mechanisms may be malfunctioning. Homeostatic synaptic plasticity is one method that neuronal circuits may employ to maintain stable electrical activity. In this proposal, we use the pyloric central pattern generating circuit of the crab Cancer borealis as a model network of stable, rhythmic activity to characterize the underlying changes in synaptic strength that occur at a particular synapse in the network, the lateral pyloric (LP) neuron to pyloric dilator (PD) neuron synapse, over the course of a long-term intracellular recording (>6 hours, up to 12 hours). When compared with synaptic strength profiles gathered during long-term activity manipulations via current injection into the PD neuron, we can determine if and to what extent homeostatic synaptic plasticity is involved in maintaining this circuit's patterned electrical output. We can then model the synaptic dynamics observed in the living system computationally to see if this form of synaptic plasticity is necessary and/or sufficient for stable network output. PUBLIC HEALTH RELEVANCE: Because this research will elucidate fundamental synaptic properties in small neural networks and will extend an already useful network model, the experiments proposed in this application will produce results that are significant in many branches of nervous system study and will be of interest to a wide range of scientists and engineers. For example, activity-dependent homeostatic regulation of synapses has significant implications for development, learning, and memory, as well as neurological disorders marked by aberrant neuronal activity, such as epilepsy, where these regulation mechanisms may be malfunctioning.