title: NEURODEVELOPMENT. Adult cortical plasticity depends on an early postnatal critical period.
abstract: Development of the cerebral cortex is influenced by sensory experience during distinct phases of postnatal development known as critical periods. Disruption of experience during a critical period produces neurons that lack specificity for particular stimulus features, such as location in the somatosensory system. Synaptic plasticity is the agent by which sensory experience affects cortical development. Here, we describe, in mice, a developmental critical period that affects plasticity itself. Transient neonatal disruption of signaling via the C-terminal domain of "disrupted in schizophrenia 1" (DISC1)—a molecule implicated in psychiatric disorders—resulted in a lack of long-term potentiation (LTP) (persistent strengthening of synapses) and experience-dependent potentiation in adulthood. Long-term depression (LTD) (selective weakening of specific sets of synapses) and reversal of LTD were present, although impaired, in adolescence and absent in adulthood. These changes may form the basis for the cognitive deficits associated with mutations in DISC1 and the delayed onset of a range of psychiatric symptoms in late adolescence.
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, CF23 3AX, UK.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Greenhill
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD 20852, USA.
authors.forename: Konrad
authors.initials: K
authors.lastname: Juczewski
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, CF23 3AX, UK.
authors.forename: Annelies M
authors.initials: AM
authors.lastname: de Haan
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, CF23 3AX, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Seaton
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, CF23 3AX, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Fox
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, CF23 3AX, UK. sbinrh@cardiff.ac.uk.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hardingham
mesh_terms: D017668:Age of Onset; D000818:Animals; D002540:Cerebral Cortex / Q000254:growth & development* / Q000503:physiopathology; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D001523:Mental Disorders / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D013629:Tamoxifen