PTEN Regulation of Local and Long-Range Connections in Mouse Auditory Cortex

Xiong, Q., Oviedo, H. V., Trotman, L. C., Zador, A. M. (2012) PTEN Regulation of Local and Long-Range Connections in Mouse Auditory Cortex. Journal of Neuroscience, 32 (5). pp. 1643-52. ISSN 0270-6474

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URL: http://www.ncbi.nlm.nih.gov/pubmed/22302806
DOI: 10.1523/jneurosci.4480-11.2012

Abstract

Autism spectrum disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN (phosphatase and tensin homolog deleted on chromosome 10). Through Cre-mediated recombination, we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long-range connectivity using channelrhodopsin-2 revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser-scanning photostimulation showed that local inputs onto PTEN-cko neurons in the auditory cortex were similarly enhanced. The hyperconnectivity caused by PTEN-cko could be blocked by rapamycin, a specific inhibitor of the PTEN downstream molecule mammalian target of rapamycin complex 1. Together, our results suggest that local and long-range hyperconnectivity may constitute a physiological basis for the effects of mutations in PTEN and possibly other ASD candidate genes.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN
diseases & disorders > mental disorders > personality disorders > autism
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL Post Doctoral Fellows
CSHL labs > Trotman lab
CSHL labs > Zador lab
Depositing User: Brian Soldo
Date Deposited: 23 Mar 2012 16:07
Last Modified: 02 May 2013 21:04
PMCID: PMC3532033
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25521

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