Format

Send to

Choose Destination
See comment in PubMed Commons below
J Physiol. 2012 Feb 15;590(4):763-76. doi: 10.1113/jphysiol.2011.219907. Epub 2011 Nov 28.

Rapid reversal of impaired inhibitory and excitatory transmission but not spine dysgenesis in a mouse model of mental retardation.

Author information

  • 1School of Clinical and Experimental Medicine (Neuronal Networks Group), College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Abstract

Intellectual disability affects 2-3% of the population: those due to mutations of the X-chromosome are a major cause of moderate to severe cases (1.8/1000 males). Established theories ascribe the cellular aetiology of intellectual disability to malformations of dendritic spines. Recent work has identified changes in synaptic physiology in some experimental models. Here, we investigated the pathophysiology of a mouse model of intellectual disability using electrophysiological recordings combined with confocal imaging of dentate gyrus granule neurons. Lack of oligophrenin-1 resulted in reductions in dendritic tree complexity and mature dendritic spine density and in evoked and spontaneous EPSCs and IPSCs. In the case of inhibitory transmission, the physiological change was associated with a reduction in the readily releasable pool and vesicle recycling which impaired the efficiency of inhibitory synaptic transmission. Acute inhibition of the downstream signalling pathway of oligophrenin-1 fully reversed the functional changes in synaptic transmission but not the dendritic abnormalities. The impaired inhibitory (as well as excitatory) synaptic transmission at frequencies associated with cognitive function suggests a cellular mechanism for the intellectual disability, because cortical oscillations associated with cognition normally depend on inhibitory neurons firing on every cycle.

PMID:
22124149
PMCID:
PMC3381309
DOI:
10.1113/jphysiol.2011.219907
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center