Takao K. Hensch 교수

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 electri

Sensory experience in early life shapes the mammalian brain. An impairment in the activity-dependent refinement of functional connections within developing visual cortex was identified here in a mouse model. Gene-targeted disruption of one isoform of glutamic acid decarboxylase prevented the competitive loss of responsiveness to an eye briefly deprived of vision, without affecting cooperative mechanisms of synapse modification in vitro. Selective, use-dependent enhancement of fast intracortical

Brain plasticity is dynamically regulated across the life span, peaking during windows of early life. Typically assessed in the physiological range of milliseconds (real time), these trajectories are also influenced on the longer timescales of developmental time (nurture) and evolutionary time (nature), which shape neural architectures that support plasticity. Properly sequenced critical periods of circuit refinement build up complex cognitive functions, such as language, from more primary modal

Experience-dependent brain plasticity typically declines after an early critical period during which circuits are established. Loss of plasticity with closure of the critical period limits improvement of function in adulthood, but the mechanisms that change the brain's plasticity remain poorly understood. Here, we identified an increase in expression of Lynx1 protein in mice that prevented plasticity in the primary visual cortex late in life. Removal of this molecular brake enhanced nicotinic ac

The shift in ocular dominance (OD) of binocular neurons induced by monocular deprivation is the canonical model of synaptic plasticity confined to a postnatal critical period. Developmental constraints on this plasticity not only lend stability to the mature visual cortical circuitry but also impede the ability to recover from amblyopia beyond an early window. Advances with mouse models utilizing the power of molecular, genetic, and imaging tools are beginning to unravel the circuit, cellular, a

The mammalian visual cortex is organized into columns. Here, we examine cortical influences upon developing visual afferents in the cat by altering intrinsic gamma-aminobutyric acid (GABA)-mediated inhibition with benzodiazepines. Local enhancement by agonist (diazepam) infusion did not perturb visual responsiveness, but did widen column spacing. An inverse agonist (DMCM) produced the opposite effect. Thus, intracortical inhibitory circuits shape the geometry of incoming thalamic arbors, suggest

The serine protease, tissue-type plasminogen activator (tPA) is a key regulator of extracellular proteolytic cascades. We demonstrate a requirement for tPA signaling in the experience-dependent plasticity of mouse visual cortex during the developmental critical period. Proteolytic activity by tPA in the binocular zone was typically increased within 2 days of monocular deprivation (MD). This regulation failed to occur in glutamic acid decarboxylase (GAD) 65 knockout mice, an animal model of impai

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (

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, wh