Picower Professor Mark Bear

Mark Bear

Picower Professor of Neuroscience
Investigator in The Picower Institute for Learning and Memory
Professor in Brain and Cognitive Sciences
Massachusetts Institute of Technology

Contact Info

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

Administrative Assistant

Nina Palisano
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.

Julius Axelrod Prize 2023

Beckman-Argyros Vision Award 2018

IPSEN Foundation Neuroscience Prize 2015

Ray Fuller Award, American Society for Pharmacology and Experimental Therapeutics, 2012

Award for Outstanding Contributions to the Study of Metabotropic Glutamate Receptors, 7th International mGluR Meeting, Taormina, Italy, 2011

Pioneer Award, FRAXA Research Foundation, 2011

William and Enid Rosen Award for Outstanding Contributions to Understanding Fragile X Syndrome, National Fragile X Foundation, 2006

Brown University Elizabeth H. Leduc Award for Teaching Excellence, 2000

Brown University Class of 2000 Barrett Hazeltine Citation for Teaching Excellence

Fogarty Senior International Fellowship, 1993

Society for Neuroscience Young Investigator Award, 1993

United States Office of Naval Research Young Investigator Award, 1988

Alfred P. Sloan Award, 1987​

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

Mark Bear wins SfN’s Julius Axelrod Prize

October 30, 2023
Picower People
Society for Neuroscience Award recognizes Professor Mark Bear’s synaptic plasticity research, its translation to potential amblyopia and autism treatments, and his career of mentorship.

Resolving a seeming contradiction, study advances understanding of visual recognition memory

September 27, 2023
Research Findings
Scientists have invested decades in piecing together how our vision is so good at recognizing what’s familiar. A new study overcomes an apparent discrepancy in data to reveal a new insight into how it works.

Spring break tours give high schoolers a chance to see science up close

March 31, 2023
Picower Events
Teens from area high schools got the chance to learn about advanced biology and brain research on field trips to MIT

Bear elected member of National Academy of Medicine

October 17, 2022
Picower People
Academy recognizes Mark Bear’s influential fundamental research on how experience shapes the brain and its relevance to neurodevelopmental diseases.

For high schoolers, summer starts with extra exposure to biomedical science

June 23, 2022
Picower People
Just before school was out for summer, high school students from Everett and Lawrence toured life sciences research labs at MIT to get information and inspiration

The model remodeler

March 14, 2022
Research Feature
A Picower Institute primer on ‘plasticity,’ the brain’s amazing ability to constantly adapt to and learn from experience

'Risky' Research

December 20, 2021
Research Feature
How bold new neuroscience research projects get off the ground

Study shows fragile X treatment can incur resistance, suggests ways around it

September 29, 2021
Research Findings
While the brain acquires resistance to continuous treatment with mGluR5 inhibitor drugs, lasting effects may still arise if dosing occurs intermittently and during a developmental critical period

Novel approach reverses amblyopia in animals

September 1, 2021
Research Findings
By temporarily suspending retinal activity in the non-amblyopic eye of animal models, neuroscientists restrengthened the visual response in the amblyopic eye, even at ages after the critical period when patch therapy fails

Summer students thrive in Picower labs

August 11, 2021
Picower People
Undergraduates from colleges across the country gain scientific training, mentorship and experience as participants in the MIT Summer Research Program

Kiki Chu
Lab Manager

Hector Jose De Jesus-Cortes
Postdoctoral Researcher

Peter Finnie
Postdoctoral Researcher

Ming-fai Fong
Postdoctoral Researcher

Dustin Hayden
Graduate Student

Max Heinrich
Graduate Student

Arnold Heynen
Senior Research Scientist

Erin Hickey
Research Tech

Patrick McCamphill
Postdoctoral Researcher

Daniel Montgomery
Graduate Student

Madison Leet
Graduate Student

Francis Reilly-Andujar
Graduate Student

Sara Simpson
Graduate Student

David Stoppel
Postdoctoral Researcher

Ingrid Van Welie
Research Scientist

Joyce Wang
Graduate Student

Eddie Weng, Ph.D.
Research Scientist

Athene Wilson-Glover
Administrative Assistant