Sandeep Datta, M.D., Ph.D.
Assistant Professor of Neurobiology
- Datta Lab
The goal of our research is to address a core problem in neurobiology — how is the brain wired to extract information from the environment and convert that information into action? Our laboratory seeks to answer this question by studying the mammalian olfactory system, which affords most animals the ability to detect and appropriately respond to crucial environmental cues. The central hypothesis of our laboratory is that the neural circuits that trigger fixed action pattern behaviors in response to ethologically-relevant odors (such as those from food, predators and mates) are both anatomically and genetically stereotyped; we plan to leverage the invariance of this specific type of neural circuit to understand how odor inputs are coupled to behavioral output centers in higher brain, which in turn will reveal principles used by genes to specify behaviors.
To address these questions we take advantage of an interdisciplinary toolkit that includes both well-established techniques — such as mouse genetics and behavioral analysis — and emerging approaches — such as two-photon laser scanning microscopy and optogenetics. These tools allow us to identify specific purified odorants that drive genetically-programmed behaviors, to define peripheral receptors for these odorants, and to characterize the functional architecture of the neural circuits that translate the activation of a specific receptor in the nose into a particular behavioral response. These circuits include well-characterized components, such as the olfactory epithelium and olfactory bulb, which trigger activity in parts of the mammalian brain whose function is just now beginning to be explored, such as the piriform cortex, the cortical amygdala and olfactory tubercle. Because these hardwired olfactory circuits do not exist in isolation but as part of a complex neural mechanism capable of associative learning and top-down modulation, we also plan to explore how the specific wiring we characterize is impinged upon by neural processes that reflect experience and internal state. Finally, the areas of the cortex implicated in generating innate odor-driven behaviors play potentially important roles in the manifestation of neuropathologies ranging from panic disorder to neurodegeneration. Identifying and characterizing the circuitry that triggers innate odor-driven behaviors will lead to insight into these serious diseases, as well as other disorders related to behavioral valence and motivation.
Behavioral stress accelerates prostate cancer development in mice. January 25, 2013. The Journal of clinical investigation.
Optical highlighter molecules in neurobiology. November 28, 2011. Current opinion in neurobiology.
Detection and avoidance of a carnivore odor by prey. June 20, 2011. Proceedings of the National Academy of Sciences of the United States of America.
Distinct representations of olfactory information in different cortical centres. March 30, 2011. Nature.
A dimorphic pheromone circuit in Drosophila from sensory input to descending output. December 2, 2010. Nature.
The Drosophila pheromone cVA activates a sexually dimorphic neural circuit. February 27, 2008. Nature.
Dual role of proapoptotic BAD in insulin secretion and beta cell survival. January 27, 2008. Nature medicine.
Diverse antiapoptotic signaling pathways activated by vasoactive intestinal polypeptide, epidermal growth factor, and phosphatidylinositol 3-kinase in prostate cancer cells converge on BAD. May 25, 2006. The Journal of biological chemistry.
BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. August 21, 2003. Nature.
Bad-deficient mice develop diffuse large B cell lymphoma. July 22, 2003. Proceedings of the National Academy of Sciences of the United States of America.
Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. November 1, 2002. Developmental cell.
The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. June 1, 2002. Developmental cell.
DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. April 19, 2002. Science (New York, N.Y.).
Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. June 1, 2001. Current opinion in neurobiology.
Cellular survival: a play in three Akts. November 15, 1999. Genes & development.
Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. November 12, 1999. Science (New York, N.Y.).
Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. October 17, 1997. Cell.
Harvard Medical School
Department of Neurobiology, WAB Room 336
200 Longwood Ave
Boston MA 02115