CAREER: Noradrenergic Regulation of Hippocampal Interneurons

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The research supported by this CAREER award examines the role of the naturally occurring neurotransmitter norepinephrine (NE) in the brain and its effects on the physiological functions of interneurons. The excitatory networks of higher brain structures, such as the hippocampus, consist primarily of relay neurons. The activity of these cells is controlled by local inhibitory synaptic interactions, mediated by a small number of specialized cells called interneurons. These interneurons are a diverse group of cells, each presumably responsible for a distinct form of synaptic inhibition. The hippocampus receives a large input of NE-containing fibers, many of which appear to form contacts with interneurons, suggesting that the noradrenergic system may regulate synaptic inhibition through direct actions on interneurons. NE has been implicated in the regulation of sleep, arousal, learning and memory, but our understanding of how different subsets of NE-responsive interneurons modulate these neural processes is incomplete.Evidence suggests that NE differentially regulates at least two discrete, functionally defined, subpopulations of inhibitory hippocampal interneurons. To test this hypothesis, this CAREER project will use an interdisciplinary approach combining electrophysiological, molecular-biological and neuroimaging techniques in the in-vitro rat hippocampus to (i) characterize the effects of NE on different populations of interneurons, (ii) identify the receptors mediating these NE responses, and (iii) determine the morphological profile of interneurons affected by NE. In addition to extending our basic understanding of how NE modulates interneuron function, the information derived from this project may yield important insights into the mechanisms underlying certain cognitive and behavioral states.This investigator will integrate education with his research efforts by developing and teaching in undergraduate- and graduate-level neuroscience courses, and participating in outreach programs to encourage more high-school and undergraduate students (especially women and minorities) to consider and pursue careers in science. As part of the continued mentoring, a team of students will be trained to conduct the proposed research. In addition, benefiting both students and other faculty, the investigator will help establish and direct an electrophysiology core facility. Thus, this CAREER award will not only advance our understanding of how NE affects hippocampal network function, but also allow for high-quality training and research facilities, providing stimulating educational experiences for both present and future generations of neuroscientists.