Brain Plasticity
Inhibitory Neurons Controlling Brain Plasticity. A class of inhibitory interneurons called “PV-cells”, which orchestrate the timing of critical periods of brain development. Here PV-cells of the mouse cortex have been labelled using Brainbow technology. {Courtesy of Luke Bogart, Dawen Cai, Jeff Lichtman & Takao Hensch}
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—or ability of the brain to change—waxes and wanes with age carries an impact far beyond neuroscience, including education policy, therapeutic approaches to developmental disorders, and strategies for recovery from brain injury in adulthood.
Windows of heightened plasticity in the course of brain development are called “critical periods.” In 1998, Professor Hensch and colleagues achieved the first direct control over critical periods in the visual system, delaying or accelerating the critical period responsible for balanced representation of left and right eye inputs in the visual cortex. Since then the Hensch Lab has identified pivotal brain molecules, cells, and circuits that orchestrate critical periods and rewire neural connections in response to environmental experience—particularly early sensory experience.
As part of the Conte Center, the lab is now using behavioral and electrophysiological readouts to characterize critical periods in the maturation of prefrontal circuits. The focus is on the role of one type of inhibitory neuron within these circuits, the PV-cell—as PV-cells are thought to control the timing of critical periods and exhibit defects in psychiatric disorders such as autism and schizophrenia. The role of PV-cells in prefrontal development and plasticity will be studied both in normal laboratory mice and mouse models of early life stress or mental illness, especially in relation to fear and anxiety behaviors. This functional data will ultimately be integrated with morphologic and genetic data from the Connectome and Imprintome projects carried out by the Lichtman, Arlotta, and Feng labs.
Recent Publications:
Critical period regulation across multiple timescales.
Reh RK, Dias BG, Nelson CA, Kaufer D, Werker JF, Kolb B, Levine JD, Hensch TK.
Proc Natl Acad Sci U S A. 2020 Sep 22;117:23242-23251. doi: 10.1073/pnas.1820836117. pubmed.
Single-nucleus RNA sequencing of mouse auditory cortex reveals critical period triggers and brakes.
Kalish BT, Barkat TR, Diel EE, Zhang EJ, Greenberg ME, Hensch TK.
Proc Natl Acad Sci U S A. 2020, 117:11744-11752. pubmed
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. September 22, 2020. 117:23298-23303 doi: 10.1073/pnas.1820847116. pubmed
CRISPR/dCas9-based Scn1a gene activation in inhibitory neurons ameliorates epileptic and behavioral phenotypes of Dravet syndrome model mice.
Yamagata T, Raveau M, Kobayashi K, Miyamoto H, Tatsukawa T, Ogiwara I, Itohara S, Hensch TK, Yamakawa K.
Neurobiol Dis. 2020 May 21;141:104954 pubmed
Reduced perceptual narrowing in synesthesia.
Maurer D, Ghloum JK, Gibson LC, Watson MR, Chen LM, Akins K,
Enns JT, Hensch TK, Werker JF.
Proc Natl Acad Sci U S A. 2020 May 5;117:10089-10096 pubmed
Ceftriaxone Treatment Preserves Cortical Inhibitory Interneuron Function via Transient Salvage of GLT-1 in a Rat Traumatic Brain Injury Model.
Hameed MQ, Hsieh TH, Morales-Quezada L, Lee HHC, Damar U, MacMullin PC, Hensch TK, Rotenberg A.
Cereb Cortex. 2019, 29:4506-4518. pubmed
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;39:4847-4863. PubMed
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;10:1917. Pubmed
Critical Period Regulation by Thyroid Hormones: Potential Mechanisms and Sex-Specific Aspects. Batista G, Hensch TK.
Front. Mol. Neurosci., 05 April 2019. 12:77. doi: 10.3389/fnmol.2019.00077 Pubmed
Structural maturation of cortical perineuronal nets and their perforating synapses revealed by superresolution imaging.
Sigal YM, Bae H, Bogart LJ, Hensch TK, Zhuang X.
Proc Natl Acad Sci U S A. 2019 Apr 2;116:7071-7076. Pubmed
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 Jun;24:828-838. Pubmed
Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.
Do KQ, Cuenod M, Hensch TK.
Schizophr Bull. 2015 Jul;41:835-46. pii: sbv065. PubMed
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;10:361-72. PubMed
Clock Genes Control Cortical Critical Period Timing.
Kobayashi Y, Ye Z, Hensch TK.
Neuron. 2015 Apr 8;86:264-75. PubMed
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 Sep 15;78:396-402. PubMed
Critical periods in speech perception: new directions.
Werker JF, Hensch TK.
Annu Rev Psychol. 2015 Jan 3;66:173-96. PubMed
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. doi: 10.1016/j.neuron.2014.06.033. PubMed
Bistable parvalbumin circuits pivotal for brain plasticity.
Hensch TK.
Cell. 2014 Jan 16;156(1-2):17-9. PubMed
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 | doi: 10.3389/fnsys.2013.00102
Balancing plasticity/stability across brain development.
Takesian AE, Hensch TK.
Prog Brain Res. 2013;207:3-34. PubMed
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. PubMed
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. PubMed
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. PubMed
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. PubMed
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. PubMed