title: Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B(-/-) mice.
abstract: Some autistic individuals exhibit abnormal development of the caudate nucleus and associative cortical areas, suggesting potential dysfunction of cortico-basal ganglia (BG) circuits. Using optogenetic and electrophysiological approaches in mice, we identified a narrow postnatal period that is characterized by extensive glutamatergic synaptogenesis in striatal spiny projection neurons (SPNs) and a concomitant increase in corticostriatal circuit activity. SPNs during early development have high intrinsic excitability and respond strongly to cortical afferents despite sparse excitatory inputs. As a result, striatum and corticostriatal connectivity are highly sensitive to acute and chronic changes in cortical activity, suggesting that early imbalances in cortical function alter BG development. Indeed, a mouse model of autism with deletions in Shank3 (Shank3B(-/-)) shows early cortical hyperactivity, which triggers increased SPN excitatory synapse and corticostriatal hyperconnectivity. These results indicate that there is a tight functional coupling between cortex and striatum during early postnatal development and suggest a potential common circuit dysfunction that is caused by cortical hyperactivity.
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Rui T
authors.initials: RT
authors.lastname: Peixoto
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Wengang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Donyell M
authors.initials: DM
authors.lastname: Croney
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yevgenia
authors.initials: Y
authors.lastname: Kozorovitskiy
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Sabatini
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000503:physiopathology; D002540:Cerebral Cortex / Q000254:growth & development* / Q000502:physiology* / Q000503:physiopathology; D003342:Corpus Striatum / Q000254:growth & development* / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009434:Neural Pathways / Q000254:growth & development / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C492356:Shank3 protein, mouse