Neurons of the mammalian brain, including the human brain, receive inputs from many different classes of other neurons. The integrative response to these various inputs determines the time course of action potential firing in the cell, its internal biochemical state, and the induction of plasticity. Thus integration of signals from multiple neurons determines both information transfer between cells and the long-term plasticity of circuits. Nevertheless, how signals arriving at multiple classes of synapses interact to determine neural responses is unclear. We propose to address this question using optical approaches to manipulate synaptic activity while reading out biochemical and electrical signals in the recipient cell. These results will inform the basic mechanisms of information processing in the brain. In addition, since specific classes of synapses are perturbed in human disease or are targeted for treatment of disease, these studies will allow us to understand the integrative mechanism of disease and its therapy.

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Brain cells communicate via the release of neurotransmitters such as glutamate, GABA and dopamine that modulate the electrical and biochemical state of each cell. Each neurotransmitter has typically been studied in isolation even though the response of the cell depends on interactions between many signaling molecules. We will use novel tools to understand the process of integration of signals from multiple neurotransmitters and mechanisms by which neural function is controlled.

National Institute of Health (NIH)
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Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
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Stewart, Randall R
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Harvard Medical School
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