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      Re-opening Windows: Manipulating Critical Periods for Brain Development

      research-article
      , Ph.D., , Ph.D.
      Cerebrum: the Dana Forum on Brain Science
      The Dana Foundation

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Editor’s note:

          The brain acquires certain skills—from visual perception to language—during critical windows, specific times in early life when the brain is actively shaped by environmental input. Scientists like Takao K. Hensch are now discovering pathways in animal models through which these windows might be re-opened in adults, thus re-awakening a brain’s youth-like plasticity. Such research has implications for brain injury repair, sensory recovery, and neurodevelopmental disorder treatment. In addition, what we know today about these critical windows of development already has enormous implications for social and educational policy .

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          Most cited references32

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          Neocortical excitation/inhibition balance in information processing and social dysfunction.

          Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
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            Rethinking schizophrenia.

            How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world's population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a century, yet there is little evidence that these treatments have substantially improved outcomes for most people with schizophrenia. These current unsatisfactory outcomes may change as we approach schizophrenia as a neurodevelopmental disorder with psychosis as a late, potentially preventable stage of the illness. This 'rethinking' of schizophrenia as a neurodevelopmental disorder, which is profoundly different from the way we have seen this illness for the past century, yields new hope for prevention and cure over the next two decades.
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              Critical period regulation.

              Neuronal circuits are shaped by experience during critical periods of early postnatal life. The ability to control the timing, duration, and closure of these heightened levels of brain plasticity has recently become experimentally accessible, especially in the developing visual system. This review summarizes our current understanding of known critical periods across several systems and species. It delineates a number of emerging principles: functional competition between inputs, role for electrical activity, structural consolidation, regulation by experience (not simply age), special role for inhibition in the CNS, potent influence of attention and motivation, unique timing and duration, as well as use of distinct molecular mechanisms across brain regions and the potential for reactivation in adulthood. A deeper understanding of critical periods will open new avenues to "nurture the brain"-from international efforts to link brain science and education to improving recovery from injury and devising new strategies for therapy and lifelong learning.
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                Author and article information

                Journal
                Cerebrum
                Cerebrum
                Cerebrum
                Cerebrum: the Dana Forum on Brain Science
                The Dana Foundation
                1524-6205
                1943-3859
                Jul-Aug 2012
                29 August 2012
                : 2012
                : 11
                Author notes

                Takao K. Hensch, Ph.D., 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 a Fulbright fellow with Dr. Wolf Singer at the Max-Planck Institute for Brain Research, before 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 in both Japan (2001 Tsukahara Prize) and the United States (2005), as well as an NIH Director’s Pioneer Award (2007). He currently directs the NIMH Silvio O. Conte Center for Basic Mental Health Research at Harvard. He serves on the editorial board of various journals, including Journal of Neuroscience, Journal of Neurodevelopmental Disorders, Neural Development, Neuroscience Research, Frontiers in Neural Circuits, and Neuron.

                Dr. Hensch’s research focuses on critical periods in brain development. By applying cellular and molecular biology techniques to neural systems, his lab identified pivotal inhibitory circuits that orchestrate structural and functional rewiring of connections in response to early sensory experience. His work affects not only the basic understanding of brain development, but also therapeutic approaches to devastating cognitive disorders later in life.

                Parizad M. Bilimoria, Ph.D., is the communications and outreach director for the NIMH Silvio O. Conte Center at Harvard University. She graduated in 2010 from the Program in Neuroscience at Harvard Medical School. Her dissertation focused on signaling pathways that orchestrate the morphological development of neurons in the cerebellum. She became excited about science writing through an internship at the Office of Communications and External Relations at Harvard Medical School and worked as a science writer for the Office of Public Affairs at Children’s Hospital Boston. She has written about the first oral therapy for multiple sclerosis while serving as a medical writer for ETHOS Health Communications. She holds a B.S./M.S. in neuroscience and a minor in creative writing from Brandeis University.

                Article
                cer-11-12
                3574806
                23447797
                aebe8306-ca46-4c65-9b59-31cbc01d4223
                Copyright 2012 The Dana Foundation All Rights Reserved
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