Sandeep Robert Datta, PhD

Department of Neurobiology, Harvard Medical School

The goal of the Datta laboratory is to address how is the brain extracts information from the environment and converts that information into action.

 

Animals in the real world have to adapt to changes in sensory cues on timescales of 1s-10s of milliseconds with behavioral responses organized at timescales of 10s-100s of milliseconds. Every time the animal changes its pose or moves its body, its sensory world is reset and has to be sampled anew. From these complex and inter-dependent sensorimotor dynamics arise adaptive patterns of moment-to-moment action that enable animals to interact with the environment in a meaningful manner. Revealing how the brain addresses this challenge requires understanding how neural codes for sensation and action are built, how they interact, and how they are decoded to facilitate the generation of organized and goal-oriented behaviors that evolve coherently over time.

 

The main hypothesis of the laboratory is that we can gain leverage on this physiological problem by studying neural circuits that underlie stimulus-driven innate behaviors. Given that olfaction is the primary sense used by most animals to communicate with their environment, we focus on characterizing those circuits that enable animals to detect and respond to olfactory cues. Sensory information propagating through this system can drive complex solitary and social behaviors, alter neuroendocrine states and act as unconditioned stimuli to facilitate learning. To understand how information about these sensory cues is translated into action, we study corticostriatal circuits responsible for expressing behavioral components and sequences, and we ask how sensory information modulates the function of these circuits. The motor behaviors elicited by odors both in the real world and in the laboratory are rich in dynamics, and offer a powerful window into how the brain creates adaptive patterns of action.

 

Although our perspective has been deeply shaped by ethology, we work in the lab and not the field. Therefore, much of our work is about bringing the field to the lab — studying mice in as naturalistic a context as we possibly can — in the belief that understanding the brain requires exploring those purposes for which the brain evolved. We use the entire armamentarium of modern neuroscience techniques, ranging from molecular genetics to machine learning, from large-scale electrophysiology to 3D behavioral imaging. Our work has identified new molecular receptors for ethologically-relevant odors, novel circuits that couple together innate and learned behaviors, organizational principles that govern the organization of sensory information in brain networks, and an underlying syntactical structure to action that is organized on the millisecond timescale, and is explicitly represented by corticostriatial circuits. Current work in the lab focuses on developing closed-loop systems that allow us to manipulate neural activity in response to freely-expressed behaviors, decoding — prying open the circuits that choose which action an animal expresses at any given moment in time, and asking how sensory information percolates into those circuits to influence the global statistics of behavior — and on better understanding how action influences sensation. By using ethology as a lever, we hope to address the fundamental problem of how the brain enables animals to interact with the world.

The Lab

Stan Pashkovski

Postdoctoral Fellow

David Bran

Graduate Student

Maria (Masha) Bloom

Graduate Student

Winthrop Gillis

Graduate Student

Neha Bhagat

Lab Manager

Veroniki (Veronica) Nikolaki

Lab Technician

Tatsuya Tsukahara

Postdoctoral Fellow

Emalee Peterson

Research Assistant

Jeffrey Markowitz

Postdoctoral Fellow

Johanna Rajotte

Co-op Student

Maya Jay

Graduate Student

Caleb Weinreb

Postdoctoral Fellow

Jeffrey Wood

Co-op Student

Alia Newman-Boulle

Co-op Student

Rockwell Anyoha

Graduate Student

Alexandra Bespalko

Co-op Student

Ayman Zeine

Senior Computer Scientist

Slater Sharp

Graduate Student

Utsab Majumdar

Visiting Master's Student

Selected Publications

Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
SR Datta, H Dudek, X Tao, S Masters, H Fu, Y Gotoh, ME Greenberg
Cell 91 (2), 231-241

Cellular survival: a play in three Akts SR Datta, A Brunet, ME Greenberg Genes & development 13 (22), 2905-2927

 

Regulation of neuronal survival by the serine-threonine protein kinase Akt
Henryk Dudek, Sandeep Robert Datta, Thomas F Franke, Morris J Birnbaum, Ryoji Yao, Geoffrey M Cooper, Rosalind A Segal, David R Kaplan, Michael E Greenberg
Science 275 (5300), 661-665

 

Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms
A Bonni, A Brunet, AE West, SR Datta, MA Takasu, ME Greenberg
Science 286 (5443), 1358-1362

 

Transcription-dependent and-independent control of neuronal survival by the PI3K–Akt signaling pathway
A Brunet, SR Datta, ME Greenberg
Current opinion in neurobiology 11 (3), 297-305

 

DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein
Hien Tran, Anne Brunet, Jill M Grenier, Sandeep R Datta, Albert J Fornace, Peter S DiStefano, Lillian W Chiang, Michael E Greenberg
Science 296 (5567), 530-534

 

14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation
SR Datta, A Katsov, L Hu, A Petros, SW Fesik, MB Yaffe, ME Greenberg
Molecular cell 6 (1), 41-51

 

BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis
Nika N Danial, Colette F Gramm, Luca Scorrano, Chen-Yu Zhang, Stefan Krauss, Ann M Ranger, Sandeep Robert Datta, Michael E Greenberg, Lawrence J Licklider, Bradford B Lowell, Steven P Gygi, Stanley J Korsmeyer
Nature 424 (6951), 952-956

 

The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt
Sandrine Humbert, Elzbieta A Bryson, Fabrice P Cordelières, Nathan C Connors, Sandeep R Datta, Steven Finkbeiner, Michael E Greenberg, Frédéric Saudou
Developmental cell 2 (6), 831-837

 

Distinct representations of olfactory information in different cortical centres
DL Sosulski, ML Bloom, T Cutforth, R Axel, SR Datta
Nature 472 (7342), 213-216

 

Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis
Sandeep Robert Datta, Ann M Ranger, Michael Z Lin, James Fitzhugh Sturgill, Yong-Chao Ma, Chris W Cowan, Pieter Dikkes, Stanley J Korsmeyer, Michael E Greenberg
Developmental cell 3 (5), 631-643

 

A BRAIN Initiative Research Team

Funded by NINDS U19NS112953

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