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Takao  Hensch, PhD

Takao Hensch, PhD
Research Center:
F.M. Kirby Neurobiology Center
Program:
Neurobiology Program
Department:
Neurology Research
Hospital Title:
Senior Research Associate in Neurology
Academic Title:
Professor of Neurology, Harvard Medical School
Research Focus Area:
Critical periods in brain development
Contact:
617-919-4650
Contact Via Email
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Research Overview

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.

About Takao Hensch

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) and leads the NUMH Silvio Conte Center on Mental Health Research at Harvard.  See more at Hensch lab webpage.

Publications

Publications powered by Harvard Catalyst Profiles
  1. Hensch TK. THE POWER OF THE INFANT BRAIN. Sci Am. 2016 Feb; 314(2):64-9.
  2. Lennartsson A, Arner E, Fagiolini M, Saxena A, Andersson R, Takahashi H, Noro Y, Sng J, Sandelin A, Hensch TK, Carninci P. Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors. Epigenetics Chromatin. 2015; 8:55.
  3. Takei Y, Kikkawa YS, Atapour N, Hensch TK, Hirokawa N. 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.
  4. Ye Z, Mostajo-Radji MA, Brown JR, Rouaux C, Tomassy GS, Hensch TK, Arlotta P. Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons. Neuron. 2015 Nov 4; 88(3):475-83.
  5. Mierau SB, Patrizi A, Hensch TK, Fagiolini M. Cell-Specific Regulation of N-Methyl-D-Aspartate Receptor Maturation by Mecp2 in Cortical Circuits. Biol Psychiatry. 2016 May 1; 79(9):746-54.
  6. Do KQ, Cuenod M, Hensch TK. Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia. Schizophr Bull. 2015 Jul; 41(4):835-46.
  7. Gurnot C, Martin-Subero I, Mah SM, Weikum W, Goodman SJ, Brain U, Werker JF, Kobor MS, Esteller M, Oberlander TF, Hensch TK. Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates. Epigenetics. 2015; 10(5):361-72.
  8. Kobayashi Y, Ye Z, Hensch TK. Clock genes control cortical critical period timing. Neuron. 2015 Apr 8; 86(1):264-75.
  9. Morishita H, Cabungcal JH, Chen Y, Do KQ, Hensch TK. Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons. Biol Psychiatry. 2015 Sep 15; 78(6):396-402.
  10. Werker JF, Hensch TK. Critical periods in speech perception: new directions. Annu Rev Psychol. 2015 Jan 3; 66:173-96.
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  12. Gogolla N, Takesian AE, Feng G, Fagiolini M, Hensch TK. Sensory integration in mouse insular cortex reflects GABA circuit maturation. Neuron. 2014 Aug 20; 83(4):894-905.
  13. Albers MW, Gilmore GC, Kaye J, Murphy C, Wingfield A, Bennett DA, Boxer AL, Buchman AS, Cruickshanks KJ, Devanand DP, Duffy CJ, Gall CM, Gates GA, Granholm AC, Hensch T, Holtzer R, Hyman BT, Lin FR, McKee AC, Morris JC, Petersen RC, Silbert LC, Struble RG, Trojanowski JQ, Verghese J, Wilson DA, Xu S, Zhang LI. At the interface of sensory and motor dysfunctions and Alzheimer's disease. Alzheimers Dement. 2015 Jan; 11(1):70-98.
  14. Hensch TK. Bistable parvalbumin circuits pivotal for brain plasticity. Cell. 2014 Jan 16; 156(1-2):17-9.
  15. Gervain J, Vines BW, Chen LM, Seo RJ, Hensch TK, Werker JF, Young AH. Valproate reopens critical-period learning of absolute pitch. Front Syst Neurosci. 2013; 7:102.
  16. Kang E, Durand S, LeBlanc JJ, Hensch TK, Chen C, Fagiolini M. Visual acuity development and plasticity in the absence of sensory experience. J Neurosci. 2013 Nov 6; 33(45):17789-96.
  17. Kobayashi Y, Hensch TK. Germline recombination by conditional gene targeting with Parvalbumin-Cre lines. Front Neural Circuits. 2013; 7:168.
  18. Hisatsune C, Miyamoto H, Hirono M, Yamaguchi N, Sugawara T, Ogawa N, Ebisui E, Ohshima T, Yamada M, Hensch TK, Hattori M, Mikoshiba K. 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.
  19. Toyoizumi T, Miyamoto H, Yazaki-Sugiyama Y, Atapour N, Hensch TK, Miller KD. A theory of the transition to critical period plasticity: inhibition selectively suppresses spontaneous activity. Neuron. 2013 Oct 2; 80(1):51-63.
  20. Sanchez-Mut JV, Aso E, Panayotis N, Lott I, Dierssen M, Rabano A, Urdinguio RG, Fernandez AF, Astudillo A, Martin-Subero JI, Balint B, Fraga MF, Gomez A, Gurnot C, Roux JC, Avila J, Hensch TK, Ferrer I, Esteller M. DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease. Brain. 2013 Oct; 136(Pt 10):3018-27.
  21. Ogiwara I, Iwasato T, Miyamoto H, Iwata R, Yamagata T, Mazaki E, Yanagawa Y, Tamamaki N, Hensch TK, Itohara S, Yamakawa K. Nav1.1 haploinsufficiency in excitatory neurons ameliorates seizure-associated sudden death in a mouse model of Dravet syndrome. Hum Mol Genet. 2013 Dec 1; 22(23):4784-804.
  22. Spatazza J, Lee HH, Di Nardo AA, Tibaldi L, Joliot A, Hensch TK, Prochiantz A. Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity. Cell Rep. 2013 Jun 27; 3(6):1815-23.
  23. Cabungcal JH, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch TK, Do KQ. Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proc Natl Acad Sci U S A. 2013 May 28; 110(22):9130-5.
  24. Takesian AE, Hensch TK. Balancing plasticity/stability across brain development. Prog Brain Res. 2013; 207:3-34.
  25. Durand S, Patrizi A, Quast KB, Hachigian L, Pavlyuk R, Saxena A, Carninci P, Hensch TK, Fagiolini M. NMDA receptor regulation prevents regression of visual cortical function in the absence of Mecp2. Neuron. 2012 Dec 20; 76(6):1078-90.
  26. Miyamoto H, Nakamaru-Ogiso E, Hamada K, Hensch TK. Serotonergic integration of circadian clock and ultradian sleep-wake cycles. J Neurosci. 2012 Oct 17; 32(42):14794-803.
  27. Weikum WM, Oberlander TF, Hensch TK, Werker JF. 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.
  28. Bilimoria PM, Hensch TK, Bavelier D. A mouse model for too much TV? Trends Cogn Sci. 2012 Nov; 16(11):529-31.
  29. Hensch TK, Bilimoria PM. Re-opening Windows: Manipulating Critical Periods for Brain Development. Cerebrum. 2012 Jul; 2012:11.
  30. Ito S, Ogiwara I, Yamada K, Miyamoto H, Hensch TK, Osawa M, Yamakawa K. Mouse with Nav1.1 haploinsufficiency, a model for Dravet syndrome, exhibits lowered sociability and learning impairment. Neurobiol Dis. 2013 Jan; 49:29-40.
  31. Beurdeley M, Spatazza J, Lee HH, Sugiyama S, Bernard C, Di Nardo AA, Hensch TK, Prochiantz A. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci. 2012 Jul 4; 32(27):9429-37.
  32. Saxena A, Wagatsuma A, Noro Y, Kuji T, Asaka-Oba A, Watahiki A, Gurnot C, Fagiolini M, Hensch TK, Carninci P. Trehalose-enhanced isolation of neuronal sub-types from adult mouse brain. Biotechniques. 2012 Jun; 52(6):381-5.
  33. Maurer D, Hensch TK. Amblyopia: background to the special issue on stroke recovery. Dev Psychobiol. 2012 Apr; 54(3):224-38.
  34. Barkat TR, Polley DB, Hensch TK. A critical period for auditory thalamocortical connectivity. Nat Neurosci. 2011 Jul 31; 14(9):1189-94.
  35. Morishita H, Miwa JM, Heintz N, Hensch TK. Lynx1, a cholinergic brake, limits plasticity in adult visual cortex. Science. 2010 Nov 26; 330(6008):1238-40.
  36. Yazaki-Sugiyama Y, Kang S, Câteau H, Fukai T, Hensch TK. Bidirectional plasticity in fast-spiking GABA circuits by visual experience. Nature. 2009 Nov 12; 462(7270):218-21.
  37. Hensch TK, Brand AH. Development. Editorial overview. Curr Opin Neurobiol. 2009 Apr; 19(2):109-11.
  38. Sugiyama S, Prochiantz A, Hensch TK. From brain formation to plasticity: insights on Otx2 homeoprotein. Dev Growth Differ. 2009 Apr; 51(3):369-77.
  39. Suzuki T, Miyamoto H, Nakahari T, Inoue I, Suemoto T, Jiang B, Hirota Y, Itohara S, Saido TC, Tsumoto T, Sawamoto K, Hensch TK, Delgado-Escueta AV, Yamakawa K. Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility. Hum Mol Genet. 2009 Mar 15; 18(6):1099-109.
  40. Plessy C, Fagiolini M, Wagatsuma A, Harasawa N, Kuji T, Asaka-Oba A, Kanzaki Y, Fujishima S, Waki K, Nakahara H, Hensch TK, Carninci P. A resource for transcriptomic analysis in the mouse brain. PLoS One. 2008; 3(8):e3012.
  41. Sugiyama S, Di Nardo AA, Aizawa S, Matsuo I, Volovitch M, Prochiantz A, Hensch TK. Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell. 2008 Aug 8; 134(3):508-20.
  42. Morishita H, Hensch TK. Critical period revisited: impact on vision. Curr Opin Neurobiol. 2008 Feb; 18(1):101-7.
  43. Hensch T, Herold U, Diers K, Armbruster D, Brocke B. Reliability of intensity dependence of auditory-evoked potentials. Clin Neurophysiol. 2008 Jan; 119(1):224-36.
  44. Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, Takeuchi T, Itohara S, Yanagawa Y, Obata K, Furuichi T, Hensch TK, Yamakawa K. 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.
  45. Katagiri H, Fagiolini M, Hensch TK. Optimization of somatic inhibition at critical period onset in mouse visual cortex. Neuron. 2007 Mar 15; 53(6):805-12.
  46. Brocke B, Armbruster D, Muller J, Hensch T, Jacob CP, Lesch KP, Kirschbaum C, Strobel A. Serotonin transporter gene variation impacts innate fear processing: Acoustic startle response and emotional startle. Mol Psychiatry. 2006 Dec; 11(12):1106-12.
  47. Illes J, Blakemore C, Hansson MG, Hensch TK, Leshner A, Maestre G, Magistretti P, Quirion R, Strata P. International perspectives on engaging the public in neuroethics. Nat Rev Neurosci. 2005 Dec; 6(12):977-82.
  48. Hensch TK. Critical period plasticity in local cortical circuits. Nat Rev Neurosci. 2005 Nov; 6(11):877-88.
  49. Hensch TK. Recovery in the blink of an eye. Neuron. 2005 Oct 20; 48(2):166-8.
  50. Bellinger FP, Hensch TK. 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.
  51. Hensch TK. Critical period mechanisms in developing visual cortex. Curr Top Dev Biol. 2005; 69:215-37.
  52. Hensch TK, Fagiolini M. Excitatory-inhibitory balance and critical period plasticity in developing visual cortex. Prog Brain Res. 2005; 147:115-24.
  53. Mataga N, Mizuguchi Y, Hensch TK. Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator. Neuron. 2004 Dec 16; 44(6):1031-41.
  54. Möhler H, Fritschy JM, Crestani F, Hensch T, Rudolph U. Specific GABA(A) circuits in brain development and therapy. Biochem Pharmacol. 2004 Oct 15; 68(8):1685-90.
  55. Fagiolini M, Fritschy JM, Löw K, Möhler H, Rudolph U, Hensch TK. Specific GABAA circuits for visual cortical plasticity. Science. 2004 Mar 12; 303(5664):1681-3.
  56. Hensch TK. Critical period regulation. Annu Rev Neurosci. 2004; 27:549-79.
  57. Miyamoto H, Hensch TK. Reciprocal interaction of sleep and synaptic plasticity. Mol Interv. 2003 Oct; 3(7):404-17.
  58. Hirozane-Kishikawa T, Shiraki T, Waki K, Nakamura M, Arakawa T, Kawai J, Fagiolini M, Hensch TK, Hayashizaki Y, Carninci P. Subtraction of cap-trapped full-length cDNA libraries to select rare transcripts. Biotechniques. 2003 Sep; 35(3):510-6, 518.
  59. Hensch TK. Controlling the critical period. Neurosci Res. 2003 Sep; 47(1):17-22.
  60. Iwai Y, Fagiolini M, Obata K, Hensch TK. Rapid critical period induction by tonic inhibition in visual cortex. J Neurosci. 2003 Jul 30; 23(17):6695-702.
  61. Carninci P, Waki K, Shiraki T, Konno H, Shibata K, Itoh M, Aizawa K, Arakawa T, Ishii Y, Sasaki D, Bono H, Kondo S, Sugahara Y, Saito R, Osato N, Fukuda S, Sato K, Watahiki A, Hirozane-Kishikawa T, Nakamura M, Shibata Y, Yasunishi A, Kikuchi N, Yoshiki A, Kusakabe M, Gustincich S, Beisel K, Pavan W, Aidinis V, Nakagawara A, Held WA, Iwata H, Kono T, Nakauchi H, Lyons P, Wells C, Hume DA, Fagiolini M, Hensch TK, Brinkmeier M, Camper S, Hirota J, Mombaerts P, Muramatsu M, Okazaki Y, Kawai J, Hayashizaki Y. Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia. Genome Res. 2003 Jun; 13(6B):1273-89.
  62. Miyamoto H, Katagiri H, Hensch T. Experience-dependent slow-wave sleep development. Nat Neurosci. 2003 Jun; 6(6):553-4.
  63. Mataga N, Nagai N, Hensch TK. Permissive proteolytic activity for visual cortical plasticity. Proc Natl Acad Sci U S A. 2002 May 28; 99(11):7717-21.
  64. Renger JJ, Hartman KN, Tsuchimoto Y, Yokoi M, Nakanishi S, Hensch TK. 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.
  65. Mataga N, Fujishima S, Condie BG, Hensch TK. 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.
  66. Fagiolini M, Hensch TK. Inhibitory threshold for critical-period activation in primary visual cortex. Nature. 2000 Mar 9; 404(6774):183-6.
  67. Hensch TK. Whisking away space in the brain. Neuron. 1999 Nov; 24(3):492-3.
  68. Artola A, Hensch T, Singer W. Calcium-induced long-term depression in the visual cortex of the rat in vitro. J Neurophysiol. 1996 Aug; 76(2):984-94.
  69. Hensch TK, Stryker MP. Ocular dominance plasticity under metabotropic glutamate receptor blockade. Science. 1996 Apr 26; 272(5261):554-7.
  70. Luo L, Hensch TK, Ackerman L, Barbel S, Jan LY, Jan YN. Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines. Nature. 1996 Feb 29; 379(6568):837-40.
  71. Ajima A, Hensch T, Kado RT, Ito M. 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.
  72. Hensch TK, Gordon JA, Brandon EP, McKnight GS, Idzerda RL, Stryker MP. 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.
  73. Fagiolini M, Katagiri H, Miyamoto H, Mori H, Grant SG, Mishina M, Hensch TK. Separable features of visual cortical plasticity revealed by N-methyl-D-aspartate receptor 2A signaling. Proc Natl Acad Sci U S A. 2003 Mar 4; 100(5):2854-9.
  74. Yang EJ, Lin EW, Hensch TK. Critical period for acoustic preference in mice. Proc Natl Acad Sci U S A. 2012 Oct 16; 109 Suppl 2:17213-20.
  75. Hensch TK, Stryker MP. Columnar architecture sculpted by GABA circuits in developing cat visual cortex. Science. 2004 Mar 12; 303(5664):1678-81.
  76. Hackett TA, Barkat TR, O'Brien BM, Hensch TK, Polley DB. Linking topography to tonotopy in the mouse auditory thalamocortical circuit. J Neurosci. 2011 Feb 23; 31(8):2983-95.
  77. Lodato S, Rouaux C, Quast KB, Jantrachotechatchawan C, Studer M, Hensch TK, Arlotta P. Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex. Neuron. 2011 Feb 24; 69(4):763-79.
  78. Hensch TK, Fagiolini M, Mataga N, Stryker MP, Baekkeskov S, Kash SF. Local GABA circuit control of experience-dependent plasticity in developing visual cortex. Science. 1998 Nov 20; 282(5393):1504-8.
  79. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schönbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y. The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2; 309(5740):1559-63.
  80. Bavelier D, Levi DM, Li RW, Dan Y, Hensch TK. Removing brakes on adult brain plasticity: from molecular to behavioral interventions. J Neurosci. 2010 Nov 10; 30(45):14964-71.
  81. Gogolla N, Leblanc JJ, Quast KB, Südhof TC, Fagiolini M, Hensch TK. Common circuit defect of excitatory-inhibitory balance in mouse models of autism. J Neurodev Disord. 2009 Jun; 1(2):172-81.
  82. Bei F, Lee HH, Liu X, Gunner G, Jin H, Ma L, Wang C, Hou L, Hensch TK, Frank E, Sanes JR, Chen C, Fagiolini M, He Z. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell. 2016 Jan 14; 164(1-2):219-32.
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