Research Topics
| MARK BEARSummaryAffiliation: Massachusetts Institute of Technology Country: USA Publications
Research Grants
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Publications
The pathophysiology of fragile X (and what it teaches us about synapses)Asha L Bhakar
Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Annu Rev Neurosci 35:417-43. 2012..This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way...
The mGluR theory of fragile X mental retardationMark F Bear
The Picower Center for Learning and Memory, Howard Hughes Medical Institute and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Trends Neurosci 27:370-7. 2004..The theory suggests new directions for basic research as well as novel therapeutic approaches for the treatment of humans with fragile X, the most frequent inherited cause of mental retardation and an identified cause of autism...- Fragile X: translation in actionMark F Bear
Department of Brain and Cognitive Sciences, Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Neuropsychopharmacology 33:84-7. 2008..Insights gained by the study of synaptic plasticity in animal models of fragile X have suggested novel therapeutic approaches, not only for human fragile X but also for autism and mental retardation of unknown etiology... - Therapeutic implications of the mGluR theory of fragile X mental retardationM F Bear
The Picower Center for Learning and Memory, Howard Hughes Medical Institute and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, 02139, USA
Genes Brain Behav 4:393-8. 2005..Abnormal mGluR signaling could be responsible for remarkably diverse psychiatric and neurological symptoms in fragile X syndrome, including delayed cognitive development, seizures, anxiety, movement disorders and obesity... 
Anatomical origins of ocular dominance in mouse primary visual cortexJ E Coleman
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Howard Hughes Medical Institute, Massachusetts Institute of Technology 46 3301, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
Neuroscience 161:561-71. 2009..Together, our findings establish that the relative density of feed-forward dLGN inputs determines the C/I response ratio of mouse binocular V1...- Altered synaptic plasticity in a mouse model of fragile X mental retardationKimberly M Huber
Department of Neuroscience, Howard Hughes Medical Institute, Brown University, Providence, RI 02912, USA
Proc Natl Acad Sci U S A 99:7746-50. 2002..This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome... - New views of Arc, a master regulator of synaptic plasticityJason D Shepherd
Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Nat Neurosci 14:279-84. 2011.... - Correction of fragile X syndrome in miceGul Dolen
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Neuron 56:955-62. 2007..Our results demonstrate that mGluR5 contributes significantly to the pathogenesis of the disease, a finding that has significant therapeutic implications for fragile X and related developmental disorders... - Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndromeEmily K Osterweil
Department of Brain and Cognitive Sciences, Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Neurosci 30:15616-27. 2010..These results suggest that the ERK1/2 pathway, and other neurotransmitter systems that stimulate protein synthesis via ERK1/2, represent additional therapeutic targets for FXS... - Synaptic plasticity in an altered stateBenjamin D Philpot
Howard Hughes Medical Institute, Department of Neuroscience, Brown University, Box 1953, Providence, RI 02912, USA
Neuron 33:665-7. 2002..The authors provide convincing evidence that the activation history of a synapse determines both the ability of a synapse to depress and the mechanism of depression... - Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndromeGul Dolen
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
J Physiol 586:1503-8. 2008..Since a reduction of mGluR5 signalling can reverse fragile X phenotypes, these studies provide a compelling rationale for the use of mGluR5 antagonists for the treatment of fragile X and related disorders... - Activation of mGluR5 induces rapid and long-lasting protein kinase D phosphorylation in hippocampal neuronsDilja D Krueger
Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, 46 3301, Cambridge, MA 02139, USA
J Mol Neurosci 42:1-8. 2010..These findings have important implications for the study of the molecular mechanisms underlying mGluR-dependent synaptic plasticity... - Essential role for a long-term depression mechanism in ocular dominance plasticityBong June Yoon
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 106:9860-5. 2009..These data suggest that AMPAR internalization is essential for the loss of synaptic strength caused by sensory deprivation in visual cortex... - Courting a cure for fragile XGul Dolen
Howard Hughes Medical Institute, The Picower Center for Learning and Memory, Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Neuron 45:642-4. 2005..As a test of this theory, McBride et al. show that in a Drosophila model for Fragile X syndrome, treatment with mGluR antagonists can rescue short-term memory, courtship, and mushroom body defects... - Rapid structural remodeling of thalamocortical synapses parallels experience-dependent functional plasticity in mouse primary visual cortexJason E Coleman
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
J Neurosci 30:9670-82. 2010..Our results support the hypothesis that the rapid plasticity of TC synapses is a key step in the sequence of events that shift OD in visual cortex... - Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expressionMarcie Colledge
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
Neuron 40:595-607. 2003..These data suggest that ubiquitination of PSD-95 through an Mdm2-mediated pathway is critical in regulating AMPA receptor surface expression during synaptic plasticity... - Bidirectional synaptic plasticity: from theory to realityMark F Bear
Howard Hughes Medical Institute, Department of Neuroscience, Brown University, Providence, RI 02912, USA
Philos Trans R Soc Lond B Biol Sci 358:649-55. 2003..The knowledge of these molecular mechanisms now promises to reveal when and how sensory experience modifies synapses in the cerebral cortex... - Toward fulfilling the promise of molecular medicine in fragile X syndromeDilja D Krueger
The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Annu Rev Med 62:411-29. 2011..The insights gained from FXS and other autism-related single-gene disorders may also assist in identifying molecular mechanisms and potential treatment approaches for idiopathic autism... - Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortexGordon B Smith
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Philos Trans R Soc Lond B Biol Sci 364:357-67. 2009..This review will discuss evidence supporting this three-stage model, along with outstanding issues in the field... - Cannabinoid receptor blockade reveals parallel plasticity mechanisms in different layers of mouse visual cortexCheng Hang Liu
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Neuron 58:340-5. 2008.... - Thalamic activity that drives visual cortical plasticityMONICA L LINDEN
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Cambridge, Massachusetts, USA
Nat Neurosci 12:390-2. 2009..Our findings substantially alter the interpretation of previous studies and define the afferent activity patterns that trigger cortical plasticity... - The ratio of NR2A/B NMDA receptor subunits determines the qualities of ocular dominance plasticity in visual cortexKathleen K A Cho
Picower Institute for Learning and Memory, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 106:5377-82. 2009..These data support the hypothesis that a reduction in the NR2A/B ratio during monocular deprivation is permissive for the compensatory potentiation of non-deprived inputs... - Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivationCortina L McCurry
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Nat Neurosci 13:450-7. 2010..These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex... - Relative contribution of feedforward excitatory connections to expression of ocular dominance plasticity in layer 4 of visual cortexLena A Khibnik
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Neuron 66:493-500. 2010..The results show that the rapid OD shift following MD is strongly expressed at the level of thalamocortical synaptic transmission... - Evidence for altered NMDA receptor function as a basis for metaplasticity in visual cortexBenjamin D Philpot
Howard Hughes Medical Institute and The Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Neurosci 23:5583-8. 2003..Finally, we show that an in vivo manipulation that rapidly downregulates NMDA receptor function in the visual cortex, brief light exposure, also rapidly reverses the effect of dark-rearing on LTD... - Loss of the fragile X mental retardation protein decouples metabotropic glutamate receptor dependent priming of long-term potentiation from protein synthesisBenjamin D Auerbach
Department of Brain and Cognitive Sciences, Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Neurophysiol 104:1047-51. 2010.... - Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1Albert Y Hung
The Institute of Physical and Chemical Research RIKEN Massachusetts Institute of Technology Neuroscience Research Center, Cambridge, Massachusetts 02139, USA
J Neurosci 28:1697-708. 2008.... - Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depressionEric M Snyder
Howard Hughes Medical Institute, The Picower Center for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Biol Chem 280:16962-8. 2005..These data indicate that synaptic anchoring of PKA through association with AKAPs plays an important role in the regulation of AMPA receptor surface expression and synaptic plasticity... - How monocular deprivation shifts ocular dominance in visual cortex of young miceMikhail Y Frenkel
Howard Hughes Medical Institute, The Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Neuron 44:917-23. 2004..Understanding how MI and MD differentially affect activity in the visual system of young mice may provide key insight into how the critical period ends... - Bidirectional modifications of visual acuity induced by monocular deprivation in juvenile and adult ratsKaren Iny
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Neurosci 26:7368-74. 2006..These findings suggest that the bidirectional changes in visually evoked responses after MD are behaviorally meaningful and that significant plasticity is exhibited well into adulthood... - Instructive effect of visual experience in mouse visual cortexMikhail Y Frenkel
The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Neuron 51:339-49. 2006..SRP requires NMDA receptor activation and is prevented by viral delivery of a peptide that interferes with AMPA receptor trafficking. SRP may reveal the mechanisms involved in certain forms of perceptual learning... - Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivationArnold J Heynen
Howard Hughes Medical Institute, The Picower Center for Learning and Memory, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Nat Neurosci 6:854-62. 2003..The mechanisms of LTD, about which there is now a detailed understanding, therefore contribute to visual cortical plasticity... - Learning induces long-term potentiation in the hippocampusJonathan R Whitlock
Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Science 313:1093-7. 2006..Because the learning-induced synaptic potentiation occluded HFS-induced LTP, we conclude that inhibitory avoidance training induces LTP in CA1... - Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortexRobert A Crozier
Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Science, Massachusetts Institute of Technology, 177 Massachusetts Avenue, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 104:1383-8. 2007..Occlusion experiments suggest that both mechanisms contribute to the loss of visual responsiveness after monocular deprivation... - NMDA receptor-dependent ocular dominance plasticity in adult visual cortexNathaniel B Sawtell
Howard Hughes Medical Institute, The Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Neuron 38:977-85. 2003..These insights may force a revision in how data on ocular dominance plasticity in mutant mice have been interpreted... - Group I metabotropic glutamate receptors: a role in neurodevelopmental disorders?Maria Vincenza Catania
Institute of Neurological Sciences, National Research Council CNR, Vl Regina Margherita 6, Catania, 95123, Italy
Mol Neurobiol 35:298-307. 2007..Drugs that block the activity of group I mGlu receptors (in particular, mGlu5 receptors) are potentially helpful for the treatment of Fragile X syndrome and perhaps other neurodevelopmental disorders... - Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1Sean M Gallagher
Center for Basic Neuroscience, Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA
J Neurosci 24:4859-64. 2004..These results point to ERK as an important regulator of mGluR-LTD and a potential mechanism for mGluR regulation of synaptic protein synthesis... - A morphological correlate of synaptic scaling in visual cortexWes Wallace
Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA
J Neurosci 24:6928-38. 2004..Thus, not all effects of dark rearing can be reversed by subsequent visual experience, even when the experience occurs during the third postnatal week... - LTP and LTD: an embarrassment of richesRobert C Malenka
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA
Neuron 44:5-21. 2004..Here we review those forms of LTP and LTD for which mechanisms have been most firmly established. Examples are provided that show how these mechanisms can contribute to experience-dependent modifications of brain function... - Stimulus for rapid ocular dominance plasticity in visual cortexCynthia D Rittenhouse
Department of Neuroscience, Brown University, Providence, Rhode Island, USA
J Neurophysiol 95:2947-50. 2006..The quality rather than the quantity of retinal illumination is the key factor for ocular dominance plasticity. These data have implications for both the mechanism and treatment of amblyopia... - Activity-dependent regulation of NR2B translation contributes to metaplasticity in mouse visual cortexWendy S Chen
Department of Neuroscience, Brown University, Box 1953, Providence, RI 02912, USA
Neuropharmacology 52:200-14. 2007..Translation of NR2A is not regulated in this manner. Therefore, the differential translational regulation of NR2A and NR2B may contribute to experience-dependent modification of NMDAR subunit composition... - Obligatory role of NR2A for metaplasticity in visual cortexBenjamin D Philpot
Curriculum in Neurobiology, Neuroscience Center, and Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, 105 Mason Farm Road, Chapel Hill, NC 27599, USA
Neuron 53:495-502. 2007..These data support the hypothesis that experience-dependent changes in NR2A/B are functionally significant and yield a mechanism for an adjustable synaptic modification threshold in visual cortex... - A unified model of NMDA receptor-dependent bidirectional synaptic plasticityHarel Z Shouval
Institute for Brain and Neural Systems, Brown University, Providence, RI 02912, USA
Proc Natl Acad Sci U S A 99:10831-6. 2002..The key assumptions and consequences of the model can be tested experimentally; further, the model provides the foundation for a unified theory of N-methyl-d-aspartate receptor-dependent synaptic plasticity...
Research Grants
- Training Program in the Neurobiology of Learning and MemoryMARK BEAR; Fiscal Year: 2007..To solve these problems, the next generation of neuroscientists will require the broad and interdisciplinary training our program is designed to provide. Funds are requested for five years to support six trainees. ..
- Mechanism/Function of Familial Mental Retardation Protein in Neuronal DevelopmentMARK BEAR; Fiscal Year: 2007..abstract not available ..
- EXPERIENCE DEPENDENT VISUAL CORTICAL DEVELOPMENTMark F Bear; Fiscal Year: 2010....
- EXPERIENCE DEPENDENT VISUAL CORTICAL DEVELOPMENTMARK BEAR; Fiscal Year: 2009....
- EXPERIENCE DEPENDENT VISUAL CORTICAL DEVELOPMENTMARK BEAR; Fiscal Year: 2001..These experiments promise to establish, for the first time in any system, which LTP and naturally occurring synaptic plasticity utilize common mechanisms. ..
- EXPERIENCE DEPENDENT VISUAL CORTICAL DEVELOPMENTMARK BEAR; Fiscal Year: 2004..These experiments promise to establish that LTP and naturally occurring synaptic plasticity utilize common mechanisms. ..
- Mechanisms and Functions of FMRP in Neuronal DevelopmentMark F Bear; Fiscal Year: 2010..Further insight gained by the studies in animal models of fragile X are likely to suggest novel therapeutic approaches, not only for human fragile X, but also for autism and mental retardation of unknown etiology. ..