RRC ID 35755
Author Tropea D, Molinos I, Petit E, Bellini S, Nagakura I, O'Tuathaigh C, Schorova L, Mitchell KJ, Waddington J, Sur M, Gill M, Corvin AP.
Title Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro.
Journal Transl Psychiatry
Abstract Major neuropsychiatric disorders are genetically complex but share overlapping etiology. Mice mutant for rare, highly penetrant risk variants can be useful in dissecting the molecular mechanisms involved. The gene disrupted in schizophrenia 1 (DISC1) has been associated with increased risk for neuropsychiatric conditions. Mice mutant for Disc1 display morphological, functional and behavioral deficits that are consistent with impairments observed across these disorders. Here we report that Disc1 L100P mutants are less able to reorganize cortical circuitry in response to stimulation in vivo. Molecular analysis reveals that the mutants have a reduced expression of PSD95 and pCREB in visual cortex and fail to adjust expression of such markers in response to altered stimulation. In vitro analysis shows that mutants have impaired functional reorganization of cortical neurons in response to selected forms of neuronal stimulation, but there is no altered basal expression of synaptic markers. These findings suggest that DISC1 has a critical role in the reorganization of cortical plasticity and that this phenotype becomes evident only under challenge, even at early postnatal stages. This result may represent an important etiological mechanism in the emergence of neuropsychiatric disorders.
Volume 6(1)
Pages e712
Published 2016-1-12
DOI 10.1038/tp.2015.206
PII tp2015206
PMID 26756905
PMC PMC5068880
MeSH Animals Behavior, Animal / physiology* Brain / physiopathology* Disease Models, Animal In Vitro Techniques Mice Mice, Inbred C57BL Mutation / genetics Nerve Tissue Proteins / genetics* Neuronal Plasticity / genetics* Neuronal Plasticity / physiology Schizophrenia / genetics Schizophrenia / physiopathology*
IF 5.28
Times Cited 6
Mice RBRC02324