Brain-specific loss of a microtubule-binding protein collapsin response mediator protein-2(CRMP2)in the mouse recapitulates many schizophrenia-like behaviors of human patients,possibly resulting from associated develo...Brain-specific loss of a microtubule-binding protein collapsin response mediator protein-2(CRMP2)in the mouse recapitulates many schizophrenia-like behaviors of human patients,possibly resulting from associated developmental deficits in neuronal differentiation,path-finding,and synapse formation.However,it is still unclear how the Crmp2 loss affects neuronal circuit function and plasticity.By conducting in vivo and ex vivo electrophysiological recording in the mouse primary visual cortex(V1),we reveal that CRMP2 exerts a key regulation on the timing of postnatal critical period(CP)for experience-dependent circuit plasticity of sensory cortex.In the developing V1,the Crmp2 deficiency induces not only a delayed maturation of visual tuning functions but also a precocious CP for visual input-induced ocular dominance plasticity and its induction activity–coincident binocular inputs right after eye-opening.Mechanistically,the Crmp2 deficiency accelerates the maturation process of cortical inhibitory transmission and subsequently promotes an early emergence of balanced excitatory-inhibitory cortical circuits during the postnatal development.Moreover,the precocious CP plasticity results in deteriorated binocular depth perception in adulthood.Thus,these findings suggest that the Crmp2 deficiency dysregulates the timing of CP for experience-dependent refinement of circuit connections and further leads to impaired sensory perception in later life.展开更多
基金the National Natural Science Foundation of China(32071025,31921002,and 31730108)the Beijing Municipal Science&Technology Commission(Z181100001518001)+1 种基金the Interdisciplinary Research Fund of Beijing Normal Universitythe Strategic Priority Research Program and Innovation Program of the Chinese Academy of Sciences(XDB32020100)。
文摘Brain-specific loss of a microtubule-binding protein collapsin response mediator protein-2(CRMP2)in the mouse recapitulates many schizophrenia-like behaviors of human patients,possibly resulting from associated developmental deficits in neuronal differentiation,path-finding,and synapse formation.However,it is still unclear how the Crmp2 loss affects neuronal circuit function and plasticity.By conducting in vivo and ex vivo electrophysiological recording in the mouse primary visual cortex(V1),we reveal that CRMP2 exerts a key regulation on the timing of postnatal critical period(CP)for experience-dependent circuit plasticity of sensory cortex.In the developing V1,the Crmp2 deficiency induces not only a delayed maturation of visual tuning functions but also a precocious CP for visual input-induced ocular dominance plasticity and its induction activity–coincident binocular inputs right after eye-opening.Mechanistically,the Crmp2 deficiency accelerates the maturation process of cortical inhibitory transmission and subsequently promotes an early emergence of balanced excitatory-inhibitory cortical circuits during the postnatal development.Moreover,the precocious CP plasticity results in deteriorated binocular depth perception in adulthood.Thus,these findings suggest that the Crmp2 deficiency dysregulates the timing of CP for experience-dependent refinement of circuit connections and further leads to impaired sensory perception in later life.
