PT  - JOURNAL ARTICLE
AU  - Qiaojie Xiong
AU  - Hysell V. Oviedo
AU  - Lloyd C. Trotman
AU  - Anthony M. Zador
TI  - PTEN Regulation of Local and Long-Range Connections in Mouse Auditory Cortex
AID  - 10.1523/JNEUROSCI.4480-11.2012
DP  - 2012 Feb 01
TA  - The Journal of Neuroscience
PG  - 1643--1652
VI  - 32
IP  - 5
4099  - http://www.jneurosci.org/content/32/5/1643.short
4100  - http://www.jneurosci.org/content/32/5/1643.full
SO  - J. Neurosci.2012 Feb 01; 32
AB  - 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.