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.
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]
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. doi: 10.1016/j.neuron.2014.06.033.
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 | doi: 10.3389/fnsys.2013.00102
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.