Novel Paradigms of Hippocampal Neuromodulation

The brain is composed of intricate circuits of neurons that communicate via electrical signals, mediated by fast excitatory or inhibitory neurotransmission on the order of milliseconds. Superimposed over this fundamental layout is a remarkably diverse set of slower signals, functioning on the order of milliseconds to hours. These instructive signals, referred to collectively as neuromodulation, critically regulate fast neurotransmission. Without neuromodulation, we would be unable to survive birth, move, eat, sleep, or love. Despite the importance of neuromodulation, our understanding of it is surprisingly limited, owing principally to several of its biological features: (1) diffuse efferent projections; (2) multiple co- released neuropeptides, with break-down products capable of receptor binding; (3) extremely broad time-scales of effect; and, (4) diverse consequences of neuromodulator action. I have recently discovered that some neuromodulators may govern activity-dependent neural circuit wiring during development. For a subset of neurons, this form of plasticity may persist into the adult. The goal of the current project is to mechanistically dissect and generalize to multiple neural systems this novel form of neuromodulatory state- dependent developmental plasticity.