Takao K. Hensch, PhD
Director of Conte Center at Harvard
Professor of Molecular and Cellular Biology, Harvard University
Professor of Neurology, Boston Children's Hospital and Harvard Medical School
Director, Child Brain Development (CIFAR), Director, IRCN (UTIAS)
Lab website: http://henschlab.mcb.harvard.edu/
Much of our adult behavior reflects the neural circuits sculpted by experience in infancy and early childhood. At no other time in life does the surrounding environment so potently shape brain function – from basic motor skills, sensation or sleep to higher cognitive processes like language. How this plasticity waxes and wanes with age carries an impact far beyond neuroscience, including education policy, therapeutic approaches to developmental disorders or strategies for recovery from brain injury in adulthood.
Our laboratory explores the mechanisms underlying critical periods of brain development. Research is aimed at the interface between cell biology and neuroscience - applying cellular/molecular techniques to elucidate complex neural systems. We have achieved the first direct control over critical period timing in the visual system (Hensch 2005). By manipulating inhibitory transmission in the neocortex, amblyopic effects of deprivation are delayed (by gene-targeted reduction of GABA synthesis) or accelerated (by cortical infusion of a positive GABA receptor modulator, diazepam).
A major goal now is to establish the generality of this principle of excitatory-inhibitory balance across brain regions and systems. Remarkably, a specific, local inhibitory circuit may drive critical period onset in visual cortex. Downstream of this trigger lies an extracellular proteolytic cascade and structural reorganizations, which ultimately consolidate plasticity.
As part of the Conte Center, we are using behavioral and electrophysiological approaches to investigate critical periods in the development of prefrontal circuits, which may be altered in mental illness. By examining mouse models of disorders such as autism or schizophrenia, or of early life stress, and integrating our functional data on critical period plasticity with connectomic and genomic data from collaborating labs, we hope to understand more holistically how brain development is disrupted in mental illness.
About Professor Hensch
Takao K. Hensch is joint professor of Neurology, Harvard Medical School at Children's Hospital Boston, and professor of Molecular and Cellular Biology at Harvard’s Center for Brain Science. After undergraduate studies with Dr. J Allan Hobson at Harvard, he was a student of Dr. Masao Ito at the University Tokyo (MPH) and Fulbright fellow with Dr. Wolf Singer at the Max-Planck Institute for Brain Research, prior to receiving a Ph.D. in neuroscience working with Dr. Michael Stryker at the University of California San Francisco in 1996. He then helped to launch the RIKEN Brain Science Institute as lab head for neuronal circuit development and served as group director (and now special advisor) before returning to the United States in 2006. Dr. Hensch has received several honors, including the Society for Neuroscience Young Investigator Award both in Japan (2001 Tsukahara Prize) and the US (2005), an NIH Director's Pioneer Award (2007), and most recently the Mortimer Sackler MD Prize (2016) for Distinguished Achievement in Developmental Psychobiology; How Early Life Experiences Shape Brain Function (Columbia University Medical Center Press Release and Weill Cornell Press Release). He currently directs an NIMH Silvio O. Conte Center for Basic Mental Health Research at Harvard. He is co-chief editor of Frontiers in Neural Circuits and serves on the editorial board of various other journals, including the Journal of Neuroscience, Neural Development, Neuroscience Research, and Neuron.
Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients.
Artoni P, Piffer A, Vinci V, LeBlanc J, Nelson CA, Hensch TK, Fagiolini M.
Proc Natl Acad Sci U S A. 2019 Jul 22. pii: 201820847. doi: 10.1073/pnas.1820847116. [Epub ahead of print]
Impaired cortico-striatal excitatory transmission triggers epilepsy.
Miyamoto H, Tatsukawa T, Shimohata A, Yamagata T, Suzuki T, Amano K, Mazaki E, Raveau M, Ogiwara I, Oba-Asaka A, Hensch TK, Itohara S, Sakimura K, Kobayashi K, Kobayashi K, Yamakawa K.
Nat Commun. 2019 Apr 23;10(1):1917.
Deletion of Neuronal GLT-1 in Mice Reveals Its Role in Synaptic Glutamate Homeostasis and Mitochondrial Function.
McNair LF, Andersen JV, Aldana BI, Hohnholt MC, Nissen JD, Sun Y, Fischer KD, Sonnewald U, Nyberg N, Webster SC, Kapur K, Rimmele TS, Barone I, Hawks-Mayer H, Lipton JO, Hodgson NW, Hensch TK, Aoki CJ, Rosenberg PA, Waagepetersen HS.
J Neurosci. 2019 Jun 19;39(25):4847-4863.
NMDA 2A receptors in parvalbumin cells mediate sex-specific rapid ketamine response on cortical activity.
Picard N, Takesian A, Fagiolini M, Hensch T
Mol Psychiatry. 2019 Jan 29. doi: 10.1038/s41380-018-0341-9. [Epub ahead of print]
Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity.
Sun H, Takesian AE, Wang TT, Lippman-Bell JJ, Hensch TK, Jensen FE.
Cell Reports 2018 23(9): 2533-2540.
Nav1.2 haplodeficiency in excitatory neurons causes absence-like seizures in mice.
Ikuo Ogiwara et al.
Communications Biology. 2018;(96)2018
Inhibitory circuit gating of auditory critical-period plasticity.
Takesian AE, Bogart LJ, Lichtman JW, Hensch TK.
Nature Neuroscience. 2018 21(2): 218-227
Critical periods in amblyopia.
Hensch TK and Quinlan EM
Vis Neurosci. 2018;Jan; 35: E014
Social Origins of Developmental Risk for Mental and Physical Illness.
Cameron JL, Eagleson KL, Fox NA, Hensch TK, Levitt P.
J. Neurosci. 2017 37(45): 10783-10791.
Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.
Steullet P, Cabungcal JH, Coyle J, Didriksen M, Gill K, Grace AA, Hensch TK, LaMantia AS, Lindemann L, Maynard TM, Meyer U, Morishita H, O’Donnell P, Puhl M, Cuenod M, Do KQ.
Mol Psychiatry. 2017 Mar 21 doi: 10.1038/mp.2017.47
Genetic Otx2 Mis-localization delays critical period plasticity across brain regions.
Lee HH, Bernard C, Ye Z, Acampora D, Simeon A, Prochiantz A, DeNardo AA, Hensch TK.
Mol Psychiatry, 2017; 1-9
Chondroitin Sulfate is Required For Onset and Offset of Critical Period Plasticity in Visual Cortex.
Hou X, Yoshioka N, Tsukano H, Sakai A, et al.
Sci Rep, 2016; 7(1):12646
Trajectory of Parvalbumin Cell Impairment and Loss of Cortical Inhibition in Traumatic Brain Injury
Hsieh T-H, Lee H, Hameed MQ, Pascual-Leone A, Hensch T, Rotenberg A.
Cerebral Cortex, 2016; 1-16
The Power of the Infant Brain
Scientific American. February 2016; 64-69.
Restoration of Visual Function by Enhancing Conduction in Regenerated Axons.
Bei F, Lee H, Liu X, Gunner G, Jin H, Ma L, Wang C, Hou I, Hensch TK, Frank E,
Sanes JR, Chen C, Fagiolini M, He Z. Cell. 2016 Jan 14; 164: 219-232.
Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors.
Lennartsson A, Arner E, Fagiolini M, Saxena A, Andersson R, Takahashi H, Noro Y, Sng J, Sandelin A, Hensch TK, Carninci P.
Epigenetics Chromatin. 2015; Dec 14;8:55.
Defects in Synaptic Plasticity, Reduced NMDA-Receptor Transport, and Instability of Postsynaptic Density Proteins in Mice Lacking Microtubule-Associated Protein 1A.
Takei Y, Kikkawa YS, Atapour N, Hensch TK, Hirokawa N.
J Neurosci. 2015 Nov 25;35(47):15539-54.
Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons.
Ye Z, Mostajo-Radji MA, Brown JR, Rouaux C, Tomassy GS, Hensch TK, Arlotta P.
Neuron. 2015 Nov 4; 88(3):475-483.
Cell-specific regulation of NMDA receptor maturation by MECP2 in cortical circuits.
Mierau SB, Patrizi A, Hensch TK, Fagiolini M.
Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.
Do KQ, Cuenod M, Hensch TK.
Schizophr Bull. 2015 Jun 1. pii: sbv065. [Epub ahead of print]
Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates.
Gurnot C, Martin-Subero I, Mah SM, Weikum W, Goodman SJ, Brain U, Werker JF, Kobor MS, Esteller M, Oberlander TF, Hensch TK.
Epigenetics. 2015 Apr 18:1-12. [Epub ahead of print]
Clock Genes Control Cortical Critical Period Timing.
Kobayashi Y, Ye Z, Hensch TK.
Neuron. 2015 Apr 8;86(1):264-75.
Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons.
Morishita H, Cabungcal JH, Chen Y, Do KQ, Hensch TK.
Biol Psychiatry. 2015 Jan 24. [Epub ahead of print]
Critical periods in speech perception: new directions.
Werker JF, Hensch TK.
Annu Rev Psychol. 2015 Jan 3;66:173-96.
Sensory Integration in Mouse Insular Cortex Reflects GABA Circuit Maturation.
Gogolla N, Takesian AE, Feng G, Fagiolini M, Hensch TK.
Neuron. 2014 Aug 20;83(4):894-905.
Bistable parvalbumin circuits pivotal for brain plasticity.
Cell. 2014 Jan 16;156(1-2):17-9.
Valproate reopens critical-period learning of absolute pitch.
Gervain J, Vines BW, Chen LM, Seo RJ, Hensch TK, Werker JF, Young AH.
Front Syst Neurosci, 2013 Dec 3.
Balancing plasticity/stability across brain development.
Takesian AE, Hensch TK.
Prog Brain Res. 2013;207:3-34.
A Theory of the Transition to Critical Period Plasticity: Inhibition Selectively Suppresses Spontaneous Activity.
Toyoizumi T, Miyamoto H, Yazaki-Sugiyama Y, Atapour N, Hensch TK, Miller KD.
Neuron. 2013 Oct 2; 80(1):51-63.
Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity.
Spatazza J, Lee HH, Di Nardo AA, Tibaldi L, Joliot A, Hensch TK, Prochiantz A.
Cell Reports. Epub 2013 June 13.
Perineuronal nets protect fast-spiking interneurons against oxidative stress.
Cabungcal JH, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch TK, Do KQ.
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9130-5.
NMDA Receptor Regulation Prevents Regression of Visual Cortical Function in the Absence of Mecp2.
Durand S, Patrizi A, Quast KB, Hachigian L, Pavlyuk R, Saxena A, Carninci P, Hensch TK, Fagiolini M.
Neuron. 2012 Dec 20;76(6):1078-90.
Critical period for acoustic preference in mice.
Yang EJ, Lin EW, Hensch TK.
Proc Natl Acad Sci U S A. 2012 Oct 16;109 Suppl 2:17213-20.
Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception.
Weikum WM, Oberlander TF, Hensch TK, Werker JF.
Proc Natl Acad Sci U S A. 2012 Oct 16;109 Suppl 2:17221-7.
IN THE NEWS:
External Press Coverage
BBC World Service: The Forum
2015 Interview for Special on Plasticity
The Elastic Brain
2015 Aeon Magazine article
A Pill For ‘Brain Youth’?
2014 NPR On Point with Tom Ashbrook Interview
Toward a Pill That Helps Us Learn as Fast as Kids
2014 Article in The Atlantic
Neurodevelopment: Unlocking the brain
2012 Nature news feature
Damaged Baby Brains—and a Video-Game Fix
2012 Chronicle of Higher Education blog Percolator
Understanding the Brain's "Brake Pedal" in Neural Plasticity
2011 Scientific American article
Vision problems in Rett syndrome could serve as biomarker
2011 Simons Foundation Autism Research Initiative story
"Lazy Eye" Treatments Provide New Insight on Brain Plasticity
2009 Scientific American article
Making an Old Brain Young
2008 Technology Review article
Plasticity: more than meets the eye
2008 Dana Foundation story
Shaping Neural Circuits by Early Experience
Prof. Hensch’s talk at the 2011 National Academy of Sciences Sackler Colloquium
Critical Periods and Brain Development
Prof. Hensch's talk at the 2011 One Mind for Research Symposium on Perception
Harvard & Children's Hospital Boston Stories
Clock genes time brain development
2015 Molecular and Cellular Biology Department news
Sensory processing problems in autism: Mice reveal brain mechanisms, treatment potential
2014 Boston Children’s research and innovations blog
Help for halting autism symptoms
2014 Harvard Gazette story
Choroid plexus a source of key factor in brain plasticity
2013 Molecular and Cellular Biology Department news
Visionary research on Rett syndrome
2012 Boston Children’s research and innovations blog
Shaping Music Preference in Mice
2012 Molecular and Cellular Biology Department news
Neurons in youth
2011 Harvard Gazette story on establishment of Conte Center
Breaking into the autistic brain
2010 Children’s Hospital Boston feature
Alzheimer’s drugs for lazy eye
2010 Children’s Hospital Boston blog Vector
Trigger for brain plasticity identified
2008 Children’s Hospital Boston news story