ABOUT THE RESEARCHER

OVERVIEW

Visit the Hensch Laboratory

Takao Hensch examines how early life experience shapes brain function.  Neural circuits are both actively sculpted and vulnerable to disorders during such “critical periods” of development.  Integrating molecular, cellular and systems neuroscience, Hensch has revealed that these periods are themselves plastic and reversible.  Specific, inhibitory (GABA) circuits determine their onset timing, and “brake”-like factors ultimately consolidate this potent rewiring process.  Translational research at Boston Children’s Hospital inspired by his work targets recovery from neurodevelopmental disorders, such as amblyopia, epilepsy and autism spectrum disorders.  See feature article in Nature for details.

BACKGROUND

Takao Hensch received his PhD from UCSF (HHMI Fellow) after training at Harvard, University of Tokyo (MPH) and the Max-Planck Institut (Fulbright Fellow).  He is a recipient of the Young Investigator Award from both the Japanese (2001 Tsukahara Prize) and US (2005) Society for Neuroscience, the NIH Director’s Pioneer Award (2007), the Mortimer D. Sackler, M.D. Prize for Distinguished Achievement in Developmental Psychobiology (2016), and leads the NIMH Silvio Conte Center on Mental Health Research at Harvard.  

PUBLICATIONS

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  1. a2-containing ?-aminobutyric acid type A receptors promote stress resiliency in male mice. Neuropsychopharmacology. 2021 Aug 18. View abstract
  2. "Scrap & build" functional circuits: Molecular and cellular basis of neural remodeling. Neurosci Res. 2021 06; 167:1-2. View abstract
  3. Kv3.1 channels regulate the rate of critical period plasticity. Neurosci Res. 2021 Jun; 167:3-10. View abstract
  4. Distributional learning of speech sound categories is gated by sensitive periods. Cognition. 2021 08; 213:104653. View abstract
  5. Increase in Seizure Susceptibility After Repetitive Concussion Results from Oxidative Stress, Parvalbumin-Positive Interneuron Dysfunction and Biphasic Increases in Glutamate/GABA Ratio. Cereb Cortex. 2020 11 03; 30(12):6108-6120. View abstract
  6. Critical period regulation across multiple timescales. Proc Natl Acad Sci U S A. 2020 09 22; 117(38):23242-23251. View abstract
  7. CRISPR/dCas9-based Scn1a gene activation in inhibitory neurons ameliorates epileptic and behavioral phenotypes of Dravet syndrome model mice. Neurobiol Dis. 2020 07; 141:104954. View abstract
  8. Single-nucleus RNA sequencing of mouse auditory cortex reveals critical period triggers and brakes. Proc Natl Acad Sci U S A. 2020 05 26; 117(21):11744-11752. View abstract
  9. Reduced perceptual narrowing in synesthesia. Proc Natl Acad Sci U S A. 2020 05 05; 117(18):10089-10096. View abstract
  10. Ceftriaxone Treatment Preserves Cortical Inhibitory Interneuron Function via Transient Salvage of GLT-1 in a Rat Traumatic Brain Injury Model. Cereb Cortex. 2019 12 17; 29(11):4506-4518. View abstract
  11. Multispectral tracing in densely labeled mouse brain with nTracer. Bioinformatics. 2019 09 15; 35(18):3544-3546. View abstract
  12. Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients. Proc Natl Acad Sci U S A. 2020 09 22; 117(38):23298-23303. View abstract
  13. Impaired cortico-striatal excitatory transmission triggers epilepsy. Nat Commun. 2019 04 23; 10(1):1917. View abstract
  14. Critical Period Regulation by Thyroid Hormones: Potential Mechanisms and Sex-Specific Aspects. Front Mol Neurosci. 2019; 12:77. View abstract
  15. Deletion of Neuronal GLT-1 in Mice Reveals Its Role in Synaptic Glutamate Homeostasis and Mitochondrial Function. J Neurosci. 2019 06 19; 39(25):4847-4863. View abstract
  16. Structural maturation of cortical perineuronal nets and their perforating synapses revealed by superresolution imaging. Proc Natl Acad Sci U S A. 2019 04 02; 116(14):7071-7076. View abstract
  17. NMDA 2A receptors in parvalbumin cells mediate sex-specific rapid ketamine response on cortical activity. Mol Psychiatry. 2019 06; 24(6):828-838. View abstract
  18. Publisher Correction: Inhibitory circuit gating of auditory critical-period plasticity. Nat Neurosci. 2018 Oct; 21(10):1495. View abstract
  19. Nav1.2 haplodeficiency in excitatory neurons causes absence-like seizures in mice. Commun Biol. 2018; 1:96. View abstract
  20. Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity. Cell Rep. 2018 05 29; 23(9):2533-2540. View abstract
  21. Inhibitory circuit gating of auditory critical-period plasticity. Nat Neurosci. 2018 02; 21(2):218-227. View abstract
  22. Critical periods in amblyopia. Vis Neurosci. 2018 01; 35:E014. View abstract
  23. PERSPECTIVE Critical periods in amblyopia-CORRIGENDUM. Vis Neurosci. 2018 01; 35:E024. View abstract
  24. Trajectory of Parvalbumin Cell Impairment and Loss of Cortical Inhibition in Traumatic Brain Injury. Cereb Cortex. 2017 12 01; 27(12):5509-5524. View abstract
  25. Social Origins of Developmental Risk for Mental and Physical Illness. J Neurosci. 2017 11 08; 37(45):10783-10791. View abstract
  26. Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex. Sci Rep. 2017 10 03; 7(1):12646. View abstract
  27. Genetic Otx2 mis-localization delays critical period plasticity across brain regions. Mol Psychiatry. 2017 05; 22(5):785. View abstract
  28. Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia. Mol Psychiatry. 2017 07; 22(7):936-943. View abstract
  29. Genetic Otx2 mis-localization delays critical period plasticity across brain regions. Mol Psychiatry. 2017 05; 22(5):680-688. View abstract
  30. THE POWER OF THE INFANT BRAIN. Sci Am. 2016 Feb; 314(2):64-9. View abstract
  31. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell. 2016 Jan 14; 164(1-2):219-232. View abstract
  32. Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors. Epigenetics Chromatin. 2015; 8:55. View abstract
  33. Defects in Synaptic Plasticity, Reduced NMDA-Receptor Transport, and Instability of Postsynaptic Density Proteins in Mice Lacking Microtubule-Associated Protein 1A. J Neurosci. 2015 Nov 25; 35(47):15539-54. View abstract
  34. Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons. Neuron. 2015 Nov 04; 88(3):475-83. View abstract
  35. Cell-Specific Regulation of N-Methyl-D-Aspartate Receptor Maturation by Mecp2 in Cortical Circuits. Biol Psychiatry. 2016 May 01; 79(9):746-754. View abstract
  36. Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia. Schizophr Bull. 2015 Jul; 41(4):835-46. View abstract
  37. Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates. Epigenetics. 2015; 10(5):361-72. View abstract
  38. Clock genes control cortical critical period timing. Neuron. 2015 Apr 08; 86(1):264-75. View abstract
  39. Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons. Biol Psychiatry. 2015 Sep 15; 78(6):396-402. View abstract
  40. Critical periods in speech perception: new directions. Annu Rev Psychol. 2015 Jan 03; 66:173-96. View abstract
  41. Sensory integration in mouse insular cortex reflects GABA circuit maturation. Neuron. 2014 Aug 20; 83(4):894-905. View abstract
  42. At the interface of sensory and motor dysfunctions and Alzheimer's disease. Alzheimers Dement. 2015 Jan; 11(1):70-98. View abstract
  43. Bistable parvalbumin circuits pivotal for brain plasticity. Cell. 2014 Jan 16; 156(1-2):17-9. View abstract
  44. Valproate reopens critical-period learning of absolute pitch. Front Syst Neurosci. 2013; 7:102. View abstract
  45. Visual acuity development and plasticity in the absence of sensory experience. J Neurosci. 2013 Nov 06; 33(45):17789-96. View abstract
  46. Germline recombination by conditional gene targeting with Parvalbumin-Cre lines. Front Neural Circuits. 2013; 7:168. View abstract
  47. IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice. Front Neural Circuits. 2013; 7:156. View abstract
  48. A theory of the transition to critical period plasticity: inhibition selectively suppresses spontaneous activity. Neuron. 2013 Oct 02; 80(1):51-63. View abstract
  49. DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease. Brain. 2013 Oct; 136(Pt 10):3018-27. View abstract
  50. Nav1.1 haploinsufficiency in excitatory neurons ameliorates seizure-associated sudden death in a mouse model of Dravet syndrome. Hum Mol Genet. 2013 Dec 01; 22(23):4784-804. View abstract
  51. Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity. Cell Rep. 2013 Jun 27; 3(6):1815-23. View abstract
  52. Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proc Natl Acad Sci U S A. 2013 May 28; 110(22):9130-5. View abstract
  53. Balancing plasticity/stability across brain development. Prog Brain Res. 2013; 207:3-34. View abstract
  54. NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2. Neuron. 2012 Dec 20; 76(6):1078-90. View abstract
  55. Serotonergic integration of circadian clock and ultradian sleep-wake cycles. J Neurosci. 2012 Oct 17; 32(42):14794-803. View abstract
  56. Critical period for acoustic preference in mice. Proc Natl Acad Sci U S A. 2012 Oct 16; 109 Suppl 2:17213-20. View abstract
  57. Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception. Proc Natl Acad Sci U S A. 2012 Oct 16; 109 Suppl 2:17221-7. View abstract
  58. A mouse model for too much TV? Trends Cogn Sci. 2012 Nov; 16(11):529-31. View abstract
  59. Re-opening Windows: Manipulating Critical Periods for Brain Development. Cerebrum. 2012 Jul; 2012:11. View abstract
  60. Mouse with Nav1.1 haploinsufficiency, a model for Dravet syndrome, exhibits lowered sociability and learning impairment. Neurobiol Dis. 2013 Jan; 49:29-40. View abstract
  61. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci. 2012 Jul 04; 32(27):9429-37. View abstract
  62. Trehalose-enhanced isolation of neuronal sub-types from adult mouse brain. Biotechniques. 2012 Jun; 52(6):381-5. View abstract
  63. Amblyopia: background to the special issue on stroke recovery. Dev Psychobiol. 2012 Apr; 54(3):224-38. View abstract
  64. A critical period for auditory thalamocortical connectivity. Nat Neurosci. 2011 Jul 31; 14(9):1189-94. View abstract
  65. Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex. Neuron. 2011 Feb 24; 69(4):763-79. View abstract
  66. Linking topography to tonotopy in the mouse auditory thalamocortical circuit. J Neurosci. 2011 Feb 23; 31(8):2983-95. View abstract
  67. Lynx1, a cholinergic brake, limits plasticity in adult visual cortex. Science. 2010 Nov 26; 330(6008):1238-40. View abstract
  68. Removing brakes on adult brain plasticity: from molecular to behavioral interventions. J Neurosci. 2010 Nov 10; 30(45):14964-71. View abstract
  69. Bidirectional plasticity in fast-spiking GABA circuits by visual experience. Nature. 2009 Nov 12; 462(7270):218-21. View abstract
  70. Development. Editorial overview. Curr Opin Neurobiol. 2009 Apr; 19(2):109-11. View abstract
  71. Common circuit defect of excitatory-inhibitory balance in mouse models of autism. J Neurodev Disord. 2009 Jun; 1(2):172-81. View abstract
  72. From brain formation to plasticity: insights on Otx2 homeoprotein. Dev Growth Differ. 2009 Apr; 51(3):369-77. View abstract
  73. Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility. Hum Mol Genet. 2009 Mar 15; 18(6):1099-109. View abstract
  74. A resource for transcriptomic analysis in the mouse brain. PLoS One. 2008 Aug 20; 3(8):e3012. View abstract
  75. Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell. 2008 Aug 08; 134(3):508-20. View abstract
  76. Critical period revisited: impact on vision. Curr Opin Neurobiol. 2008 Feb; 18(1):101-7. View abstract
  77. Reliability of intensity dependence of auditory-evoked potentials. Clin Neurophysiol. 2008 Jan; 119(1):224-36. View abstract
  78. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci. 2007 May 30; 27(22):5903-14. View abstract
  79. Optimization of somatic inhibition at critical period onset in mouse visual cortex. Neuron. 2007 Mar 15; 53(6):805-12. View abstract
  80. Serotonin transporter gene variation impacts innate fear processing: Acoustic startle response and emotional startle. Mol Psychiatry. 2006 Dec; 11(12):1106-12. View abstract
  81. International perspectives on engaging the public in neuroethics. Nat Rev Neurosci. 2005 Dec; 6(12):977-82. View abstract
  82. Critical period plasticity in local cortical circuits. Nat Rev Neurosci. 2005 Nov; 6(11):877-88. View abstract
  83. Recovery in the blink of an eye. Neuron. 2005 Oct 20; 48(2):166-8. View abstract
  84. The transcriptional landscape of the mammalian genome. Science. 2005 Sep 02; 309(5740):1559-63. View abstract
  85. Differential Distribution of NMDA and AMPA Receptor Activity in Layer II/III in Mouse Primary Visual Cortex. Microsc Microanal. 2005 Aug; 11 Suppl 2:1124-5. View abstract
  86. Critical period mechanisms in developing visual cortex. Curr Top Dev Biol. 2005; 69:215-37. View abstract
  87. Excitatory-inhibitory balance and critical period plasticity in developing visual cortex. Prog Brain Res. 2005; 147:115-24. View abstract
  88. Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator. Neuron. 2004 Dec 16; 44(6):1031-41. View abstract
  89. Specific GABA(A) circuits in brain development and therapy. Biochem Pharmacol. 2004 Oct 15; 68(8):1685-90. View abstract
  90. Columnar architecture sculpted by GABA circuits in developing cat visual cortex. Science. 2004 Mar 12; 303(5664):1678-81. View abstract
  91. Specific GABAA circuits for visual cortical plasticity. Science. 2004 Mar 12; 303(5664):1681-3. View abstract
  92. Critical period regulation. Annu Rev Neurosci. 2004; 27:549-79. View abstract
  93. Reciprocal interaction of sleep and synaptic plasticity. Mol Interv. 2003 Oct; 3(7):404-17. View abstract
  94. Subtraction of cap-trapped full-length cDNA libraries to select rare transcripts. Biotechniques. 2003 Sep; 35(3):510-6, 518. View abstract
  95. Controlling the critical period. Neurosci Res. 2003 Sep; 47(1):17-22. View abstract
  96. Rapid critical period induction by tonic inhibition in visual cortex. J Neurosci. 2003 Jul 30; 23(17):6695-702. View abstract
  97. Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia. Genome Res. 2003 Jun; 13(6B):1273-89. View abstract
  98. Experience-dependent slow-wave sleep development. Nat Neurosci. 2003 Jun; 6(6):553-4. View abstract
  99. Separable features of visual cortical plasticity revealed by N-methyl-D-aspartate receptor 2A signaling. Proc Natl Acad Sci U S A. 2003 Mar 04; 100(5):2854-9. View abstract
  100. Permissive proteolytic activity for visual cortical plasticity. Proc Natl Acad Sci U S A. 2002 May 28; 99(11):7717-21. View abstract
  101. Experience-dependent plasticity without long-term depression by type 2 metabotropic glutamate receptors in developing visual cortex. Proc Natl Acad Sci U S A. 2002 Jan 22; 99(2):1041-6. View abstract
  102. Experience-dependent plasticity of mouse visual cortex in the absence of the neuronal activity-dependent marker egr1/zif268. J Neurosci. 2001 Dec 15; 21(24):9724-32. View abstract
  103. Inhibitory threshold for critical-period activation in primary visual cortex. Nature. 2000 Mar 09; 404(6774):183-6. View abstract
  104. Whisking away space in the brain. Neuron. 1999 Nov; 24(3):492-3. View abstract
  105. Local GABA circuit control of experience-dependent plasticity in developing visual cortex. Science. 1998 Nov 20; 282(5393):1504-8. View abstract
  106. Comparison of plasticity in vivo and in vitro in the developing visual cortex of normal and protein kinase A RIbeta-deficient mice. J Neurosci. 1998 Mar 15; 18(6):2108-17. View abstract
  107. Calcium-induced long-term depression in the visual cortex of the rat in vitro. J Neurophysiol. 1996 Aug; 76(2):984-94. View abstract
  108. Ocular dominance plasticity under metabotropic glutamate receptor blockade. Science. 1996 Apr 26; 272(5261):554-7. View abstract
  109. Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines. Nature. 1996 Feb 29; 379(6568):837-40. View abstract
  110. Differential blocking action of Joro spider toxin analog on parallel fiber and climbing fiber synapses in cerebellar Purkinje cells. Neurosci Res. 1991 Oct; 12(1):281-6. View abstract
  111. The role of cerebellar flocculus in adaptive gain control of ocular reflexes. Acta Otolaryngol Suppl. 1991; 481:234-6. View abstract