Dept.: Professor, Department of Biochemistry; Investigator, HHMI; Adjunct Professor, Genome Sciences
Neuroscience Focus Groups: Behavioral Neuroscience
Our laboratory uses mouse genetic models and viral gene transfer to dissect neural circuits involved in innate behaviors. We start by making genetically engineered mice that target expression of Cre recombinase to genes that are expressed in specific subsets of neurons, typically genes encoding neuropeptides or their receptors. We then stereotaxically inject viruses expressing Cre-dependent genes (e.g., genes encoding fluorescent proteins, genes that allow activation or inhibition of neuron activity by light or chemicals, or genes that prevent all neurotransmission or kill neurons) into brain regions of interest. The aims of these studies are to (a) visualize where the neurons are located and where they project their axons, (b) record the activity of neurons in real time based on calcium-induced fluorescence, (c) evaluate the behavioral/physiological consequences of activating or inhibiting those neurons either transiently or permanently. We use combinations of these techniques to delineate neuronal circuits that control specific behaviors. For example, selective stimulation of neurons that express agouti-related protein (AgRP) promotes feeding, whereas stimulating a different population of neurons that express calcitonin gene-related peptide (CGRP) inhibits feeding. The CGRP neurons that reside in the parabrachial nucleus mediate virtually every threat that we have examined, including real threats (pain, itch, food poisoning) to potential threats (novel food, or cues that have been associated with pain). These CGRP neurons have been shown to mediate the unconditioned stimulus in classical taste- and fear-conditioning experiments. Consequently, they are important for generating taste and fear memories. Current experiments are directed towards identifying the relevant downstream targets of CGRP neurons and discerning how they are involved in mounting appropriate responses to various threats. We are also interested in the functions of other neurons that reside in the parabrachial nucleus that transmit taste, temperature, salt and water balance signals to the forebrain.