Board of Honors Tutors
James Quattrochi
Harvard Medical School
Assistant Professor of Neuroscience
Associate of Dunster House
Senior Fellow of Francis Weld Peabody Society
Department: Department of Psychiatry
Office: MMHI/HMS Neuroscience S128
74 Fenwood
Boston MA 02115
Phone: 617-232-8621/617-626-9480
Fax: 508-300-5639
jq@hms.harvard.edu
MBB Areas of Interest:
autonomic processes during sleep
brain mapping (3-D image reconstruction)
consciousness
electrophysiology
gene expression
interfaculty collaboration in instructional technologies
mind-body experience
mind-brain interaction
nanosphere pharmacology
REM sleep-wake control
MBB Undergraduate Tracks:
Cognitive Neuroscience Track
Neurobiology Track
Description of Research Interests:
Cellular and molecular mechanisms of REM sleep control. The cholinergic system, particularly the cell groups of the laterodorsal and pedunculopontine tegmental nuclei within the brain stem pontomesencephalic tegmentum, is actively involved in the timing and quantity of rapid eye movement (REM) sleep. Recent work in our laboratory has lead to two important discoveries: 1) cholinergically induced long-term enhancement of REM sleep; and 2) long-term enhancement of ponto-geniculo-occipital (PGO) waves that are a distinguishing phasic component of REM. Our focus is to determine which neurons demonstrate unique patterns of neuronal activity in association with a single point source injection of the cholinergic agonist carbachol into the caudolateral brain stem that produces these long-term effects. Our central hypothesis is that cholinergic activation of sites in the caudolateral pontomesencephalic tegmentum alters the postsynaptic excitability of the REM sleep and PGO networks by stimulating the prolonged expression of early genes that potentiates these long-term effects. Our model system of the caudolateral brain stem as a REM sleep regulatory region is tested by using pharmacologically active, epifluorescent nanosphere probes that we developed for labeling afferent neurons following pharmacological stimulation of the brain. We then determine the pattern of activation of neurons as evidenced by c-fos gene expression during these long-term behavioral state effects. Connectivity among neurons that are activated, the neurotransmitters they contain, and the signaling induction path of CREB-mediated transcription are being examined using a combination of c-fos and pCREB immunohistochemistry with anterograde dextran and retrograde nanosphere labeling. The effects on these long-term phenomena following suppression of Fos mRNA are also being studied by performing in vivo microinjections of c-fos antisense oligonucleotides. These studies should provide a basis for understanding the cellular and molecular mechanisms by which neurons in the caudolateral brain stem activate state-dependent neuronal networks involved in the long-lasting maintenance of REM sleep and PGO activity. The implications extend beyond sleep to all adaptive behavioral states in which neuronal systems must react in a unified way to reset their activation levels and to how acute synaptic events in one part of the brain trigger alterations in gene product at remote sites.
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