The primary goal of my research is to better understand the process of synaptic transmission. Typically, electrical recordings of neurons in the mammalian brain are restricted to postsynaptic neurons and presynaptic activity is inferred from postsynaptic responses. A notable exception is the calyx of Held, which permits patch clamp recording of a CNS nerve terminal to study presynaptic electrical activity. Paired nerve terminal and somatic recordings allow simultaneous measurements of pre- and postsynaptic activity. In addition, I use capacitance recordings to measure changes in membrane area to study the mechanisms of exocytosis and endocytosis. This preparation allows innovative experiments, and collaborations across disciplines. Using the calyx, I recently demonstrated that small currents, physiologically produced in nerve terminals, travel up the axon a significant distance, ~500 µm, to inhibit or facilitate action potential generation (Paradiso and Wu, Nature Neuroscience, 2009). This finding indicates that nerve terminals do not simply receive action potentials, but can also send electrical signals back toward the soma to affect action potential generation. The calyx of Held has been used to study a variety of presynaptic processes such as presynaptic degeneration, nitric oxide signaling, plasticity, presynaptic calcium, and analog signaling. My proposed experiments will determine how currents associated with action potentials affect neurotransmitter release in the presynaptic terminal. These studies will be done at an early and later stage of development to determine if synapse maturation alters the effects of these currents. Future experiments will involve using the calyx of Held, and other nerve terminals, to study presynaptic neuropathology.