PTEN regulation of local and long-range connections in mouse auditory cortex.
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.
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Qiaojie
Q
Xiong
Hysell V
HV
Oviedo
Lloyd C
LC
Trotman
Anthony M
AM
Zador
D000818:Animals; D001303:Auditory Cortex / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse