title: SYNGAP1 links the maturation rate of excitatory synapses to the duration of critical-period synaptic plasticity.
abstract: Critical periods of developmental plasticity contribute to the refinement of neural connections that broadly shape brain development. These windows of plasticity are thought to be important for the maturation of perception, language, and cognition. Synaptic properties in cortical regions that underlie critical periods influence the onset and duration of windows, although it remains unclear how mechanisms that shape synapse development alter critical-period properties. In this study, we demonstrate that inactivation of a single copy of syngap1, which causes a surprisingly common form of sporadic, non-syndromic intellectual disability with autism in humans, induced widespread early functional maturation of excitatory connections in the mouse neocortex. This accelerated functional maturation was observed across distinct areas and layers of neocortex and directly influenced the duration of a critical-period synaptic plasticity associated with experience-dependent refinement of cortical maps. These studies support the idea that genetic control over synapse maturation influences the duration of critical-period plasticity windows. These data also suggest that critical-period duration links synapse maturation rates to the development of intellectual ability.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Clement
authors.forename: Emin D
authors.initials: ED
authors.lastname: Ozkan
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aceti
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Miller
authors.forename: Gavin
authors.initials: G
authors.lastname: Rumbaugh
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000502:physiology; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D003423:Critical Period, Psychological; D003627:Data Interpretation, Statistical; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D019579:Neocortex / Q000254:growth & development / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012919:Social Behavior; D013569:Synapses / Q000502:physiology*; D013788:Thalamus / Q000254:growth & development / Q000502:physiology; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C484512:Syngap1 protein, mouse; D020703:ras GTPase-Activating Proteins