Picower Professor Mark Bear

Mark Bear

Picower Professor of Neuroscience

Contact Info

Office: 46-3301
Phone: 617-324-7002
Email: mbear@mit.edu
Website: Bear Lab

Administrative Assistant

Jessica Buckey
Office: 46-3301
Phone: 617-324-7003

How is the brain modified by experience, deprivation and disease?

Our overarching interest is in the question of how experience and deprivation modify synaptic connections in the brain. Experience-dependent synaptic plasticity is the physical substrate of memory, sculpts connections during postnatal development to determine the capabilities and limitations of brain functions, is responsible for the reorganization of the brain after damage, and is vulnerable in numerous psychiatric and neurological diseases and contributes to their symptoms.

Historically, our major efforts to address this question have been focused on the visual cortex and hippocampus. The visual cortex is a site of robust experience-dependent synaptic plasticity, exemplified by the consequences of temporary monocular deprivation (MD) during childhood. MD sets in motion a stereotyped choreography of synaptic modification whereby the deprived-eye inputs to visual cortex rapidly lose strength and, with a delay, the open-eye inputs undergo a compensatory gain in strength. The behavioral consequence of this plasticity is severe visual impairment in the deprived eye. In humans, this condition is called amblyopia, responsible for loss of vision in over 1% of the world population. Thus, the visual cortex is an excellent preparation to connect the elementary molecular mechanisms of synaptic plasticity to their behavioral consequences. Further, insights into how synapses depress or potentiate have potential clinical applications for the treatment of amblyopia.

The hippocampus is a cortical structure that is critical to forms of learning and memory. The simple cellular architecture of the hippocampus also makes it amenable to electrophysiological investigations of synaptic plasticity that are much more difficult in other parts of the brain. In the early 1990’s we applied insights gained from a theoretical analysis of synaptic plasticity to establish a phenomenon called homosynaptic long-term depression (LTD). LTD is the functional inverse of long-term synaptic potentiation (LTP). Although LTD and LTP are expressed at synapses throughout the brain, they are particularly robust at the Schaffer collateral synapses in the CA1 region of hippocampus. The hippocampus is therefore an excellent preparation to dissect the molecular basis of bidirectional synaptic plasticity. Insights gained here can not only be applied to synaptic modifications elsewhere in the brain, they are also relevant to understanding the basis of hippocampus-dependent memory storage and diseases of cognition.

In the course of studying LTD we made a discovery that has turned out to have major therapeutic significance for human developmental brain disorders that cause autism. One form of hippocampal LTD is triggered by activation of metabotropic glutamate receptor 5 (mGluR5) and requires immediate translation of mRNAs at synapses. In the course of studying this type of synaptic plasticity, we discovered that protein synthesis (and LTD) downstream of mGluR5 is exaggerated in the mouse model of fragile X (FX). Human FX is caused by the silencing of the FMR1 gene, and is the most common inherited form of intellectual disability and autism. Insight gained by the study of LTD suggested that exaggerated protein synthesis downstream of mGluR5 might be pathogenic, and contribute to many symptoms of the disease. Subsequent tests of the “mGluR theory” have shown that inhibition of mGluR5 can correct multiple mutant phenotypes in animal models of fragile X ranging from mouse to fruit fly. Human clinical trials were initiated based on the strength of this science, and results to date indicate that treatments can be developed to substantially benefit this patient population. The mGluR theory has contributed to a major paradigm shift that genetic diseases of brain development, historically viewed as untreatable, may be ameliorated or corrected with appropriate therapy.

Current work in the laboratory is focused on two related themes: (1) mechanisms and regulation of naturally occurring synaptic plasticity in visual cortex, and (2) pathophysiology of genetically defined developmental brain disorders. We primarily study mouse models, and we use a broad range of methods that include but are not limited to brain slice electrophysiology and biochemistry, in vivo electrophysiology and 2-photon functional and structural imaging, and behavioral analysis. Our lab is “question oriented” rather than “method oriented”. We will apply any technology that is needed to address the questions of greatest interest.

Mark F. Bear received his Ph.D. in neurobiology from Brown University. He took postdoctoral training from Wolf Singer at the Max Planck Institute for Brain Research in Frankfurt, Germany, and from Leon Cooper at Brown. He joined the faculty of the Brown University School of Medicine in 1985 and was named a Howard Hughes Medical Investigator in 1996. At Brown, he was awarded the 2000 Elizabeth H. Leduc Award for teaching excellence in the life sciences, and the Class of 2000 Barrett Hazeltine Citation for teaching excellence. In 2003, he was appointed Picower Professor of Neuroscience at The Picower Institute for Learning and Memory in the Department of Brain and Cognitive Sciences at MIT.

  • 2018 Beckman-Argyros Vision Research Award
  • Alfred P. Sloan Award
  • United States Office of Naval Research Young Investigator Award
  • Society for Neuroscience Young Investigator Award
  • Brown University Class of 2000 Barrett Hazeltine Citation for Teaching Excellence
  • William and Enid Rosen Award for Outstanding Contributions to Understanding Fragile X Syndrome, National Fragile X Foundation
  • Pioneer Award, FRAXA Research Foundation
  • Award for Outstanding Contributions to the Study of Metabotropic Glutamate Receptors, 7th International mGluR Meeting, Taormina, Italy
  • Ray Fuller Award, American Society for Pharmacology and Experimental Therapeutics
Featured publications are below. For a full list visit the lab website linked above.

December 6, 2016
Fong MF, Mitchell DE, Duffy KR, Bear MF. Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):14139-14144.
January 19, 2015
Cooke SF, Komorowski RW, Kaplan ES, Gavornik JP, Bear MF, Nat Neurosci. 2015 Feb;18(2):262-71.
March 23, 2014
Gavornik JP, Bear MF, Nat Neurosci. 2014 May;17(5):732-7
January 23, 2013
Emily K. Osterweil, Shih-Chieh Chuang, Alexander A. Chubykin, Michael Sidorov, Riccardo Bianchi, Robert K.S. Wong, Mark F. Bear, . Neuron. 2013;77(2):243-250
November 23, 2011
Auerbach, B.D., Osterweil, E.K., and Bear, M.F., Nature. 2011; 480, 63-68

Study probing visual memory, amblyopia unveils many-layered mystery

December 13, 2019
Research Findings
Plasticity underlying amblyopia found in visual cortex layer 4

Memory and its meaning

October 7, 2019
News Feature
25 Years of Picower Institute research

Antidepressant restores youthful flexibility to aging inhibitory neurons in mice

August 20, 2018
Research findings
Neural plasticity, dendrite growth decline with age, study finds

Beckman Foundation Names Mark Bear as 2018 Beckman-Argyros Vision Research Award Winner

August 7, 2018
Picower People
Newly Funded Research Supports Recovery from Amblyopia

The Developing Brain

July 11, 2018
News feature
Development research yields discoveries, insights, innovations

"What made me aware I wanted to study the brain?"

March 18, 2018
Brain Awareness Week 2018
Picower Institute researchers discuss their early inspiration

Improved Social Interaction and Cognition in Mouse Models of Autism Spectrum Disorder

October 26, 2017
Research Findings
Studies in mice show promise for human treatment of 16p11.2 deletion syndrome

Creating new treatments for amblyopia

November 21, 2016
Research Findings
Study finds decreasing activity in the eye can help overcome visual impairment.

Kiki Chu
Lab Manager

Hector Jose De Jesus-Cortes
Postdoctoral Researcher

Peter Finnie
Postdoctoral Researcher

Ming-fai Fong
Postdoctoral Researcher

Dustin Hayden
Graduate Student

Arnold Heynen
Senior Research Scientist

Erin Hickey
Research Tech

Taekeun Kim
Graduate Student

Patrick McCamphill
Postdoctoral Researcher

Daniel Montgomery
Graduate Student

Emily Osterweil
Research Affiliate

Antonina Palisano
Administrative Assistant

David Stoppel
Postdoctoral Researcher

Aurore Thomazeau
Postdoctoral Researcher

Ingrid Van Welie
Research Scientist

Massachusetts Institute of Technology
43 Vassar Street, Bldg. 46-1303
Cambridge, MA 02139
(+1) 617-324-0305
(+1) 617-452-2588