DESCRIPTION (provided by applicant): At excitatory synapses onto CA1 pyramidal cells, short-term plasticity causes synaptic strength to be modulated over a wide range in response to irregular stimulus patterns such as these synapses receive in vivo. This frequency-dependence of synaptic transmission enables computation at synapses, and determines the content of information transmitted between the pre- and post-synaptic cells. Very little is known, however, about short-term plasticity and frequency-dependence of synaptic transmission at excitatory synapses onto CA1 interneurons. Like CA1 pyramidal cells, interneurons in CA1 receive inputs from CA3 pyramidal cells via Schaffer collateral axons. However, the role of interneurons in the hippocampal circuit is quite different. Since these cells provide critical feed forward inhibition to the CA1 pyramidal cells, the frequency-dependence of their excitatory inputs will be crucial in determining the balance of excitation and inhibition in the circuit. The balance between inhibition and excitation is critical to the hippocampus, a brain region that is highly susceptible to epilepsy. Experiments in this proposal use electrophysiology to compare short-term plasticity and the frequency dependence of synaptic transmission at excitatory synapses onto CA1 interneurons vs. pyramidal cells, using traditional stimulus paradigms and temporally complex stimulus patterns based on in vivo recordings of action potential timing. These experiments will provide information about the role of the postsynaptic target cell in determining presynaptic properties, and how the frequency dependence of synaptic transmission is related to neural coding.