Xiong, Q., Oviedo, H. V., Trotman, L. C., Zador, A. M. (February 2012) PTEN Regulation of Local and Long-Range Connections in Mouse Auditory Cortex. Journal of Neuroscience, 32 (5). pp. 1643-52. ISSN 0270-6474
Preview |
PDF (Paper)
Trotman and Zador J Neurosci 2012.pdf - Published Version Download (2MB) | Preview |
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: | 1 February 2012 |
| Date Deposited: | 23 Mar 2012 16:07 |
| Last Modified: | 02 May 2013 21:04 |
| PMCID: | PMC3532033 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/25521 |
Actions (login required)
 |
Administrator's edit/view item |