| First Author | Xiong Q | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 5 | Pages | 1643-52 |
| PubMed ID | 22302806 | Mgi Jnum | J:181347 |
| Mgi Id | MGI:5311071 | Doi | 10.1523/JNEUROSCI.4480-11.2012 |
| Citation | Xiong Q, et al. (2012) PTEN regulation of local and long-range connections in mouse auditory cortex. J Neurosci 32(5):1643-52 |
| abstractText | 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. |
