Bernardo L. Sabatini
Department of Neurobiology, Harvard Medical School
Investigator, Howard Hughes Medical Institute
The main focus of my research laboratory is to understand the development and regulation of synapses in the brain and the relationship of these processes to behavior and disease.
In the first few years of life, humans tremendously expand their behavior repertoire and gain the ability to engage in complex, learned, and reward-driven actions. Similarly, in the few weeks after birth, mice gain the ability to perform sophisticated spatial navigation, forage independently for food, and to engage in reward reinforcement learning. Our laboratory seeks to uncover the mechanisms of synapse and circuit plasticity that permit new behaviors to be learned and refined. We are interested both in the developmental changes that occur after birth that make learning possible as well in the circuit changes that are triggered by the process of learning. We examine these processes in the cerebral cortex, the hippocampus, and the basal ganglia, crucial structures for the processing of sensory information, for associative learning and spatial navigation, and for goal-direct locomotion. In order to accomplish these studies, we rely heavily on optical approaches to examine and manipulate synapses and circuits in relatively intact brain tissue and we design and build microscopes as necessary for our research. Studies are typically performed in brain slices or awake-behaving mice and utilize a variety of genetic, biochemical, and electrophysiological approaches. Lastly, we use these same approaches and the knowledge gained from the study of normal circuit development to uncover perturbations of cell and synapse function that may contribute to human neuro-psychiatric disorders, including autism, Parkinson‘s disease, and Alzheimer‘s disease.
Our studies include analysis of:
The biophysical processes that control the function of individual synapses.
The mechanisms of regulation of synapses and neurons by neuromodulators such as dopamine, acetylcholine, and peptides.
The relationship between synaptic plasticity and behavior.
The role of perturbed synapse function in human neuropsychiatric diseases such as autism, Parkinson’s and Alzheimer’s.
Our studies are performed in the mammalian brain and we focus on the analysis of hippocampus, cortex, and basal ganglia. Recently, the analysis of the basal ganglia has become a major focus of the laboratory and we hope to perform a comprehensive analysis of the questions above in this brain structure. Lastly, as necessary for our studies, we develop novel optical, electrophysiological, and behavioral approaches to carry out the proposed work.
Wallace ML, Saunders A, Huang KW, Philson AC, Goldman M, Macosko EZ, McCarroll SA, Sabatini BL. Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia. Neuron. 2017;94 (1) :138-152.
Pisanello F, Mandelbaum G, Pisanello M, Oldenburg IA, Markowitz JE, Peterson RE, Patria DA, Haynes TM, Emara MS, Spagnolo B, et al. Dynamic illumination of spatially restricted or large brain volumes via a single tapered optical fiber. Nature Neuroscience. 2017;20 (8) :1180-1190.
Hou XH, Hyun M, Taranda J, Huang KW, Todd E, Feng D, Atwater E, Croney D, Zeidel ML, Osten P, et al. Central Control Circuit for Context-Dependent Micturition. Cell. 2016;167 (1) :73-86.
Kong D, Dagon Y, Campbell JN, Guo Y, Yang Z, Yi X, Aryal P, Wellenstein K, Kahn BB, Sabatini BL, et al. A Postsynaptic AMPK→p21-Activated Kinase Pathway Drives Fasting-Induced Synaptic Plasticity in AgRP Neurons. Neuron. 2016;91 (1) :25-33.
Straub C, Saulnier JL, Bègue A, Feng DD, Huang KW, Sabatini BL. Principles of Synaptic Organization of GABAergic Interneurons in the Striatum. Neuron. 2016;92 (1) :84-92.
Peixoto RT, Wang W, Croney DM, Kozorovitskiy Y, Sabatini BL. Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B(-/-) mice. Nature Neuroscience. 2016;19 (5) :716-724.
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