Pten knockdown in vivo increases excitatory drive onto dentate granule cells

117Citations
Citations of this article
155Readers
Mendeley users who have this article in their library.

Abstract

Some cases of autism spectrum disorder have mutations in the lipid phosphatase, phosphatase and tensin homolog on chromosome 10 (Pten). Tissue specific deletion of Pten in the hippocampus and cortex of mice causes anatomical and behavioral abnormalities similar to human autism. However, the impact of reductions in Pten on synaptic and circuit function remains unexplored. We used in vivo stereotaxic injections of lentivirus expressing a short hairpin RNA to knock down Pten in mouse neonatal and young adult dentate granule cells. We then assessed the morphology and synaptic physiology between 2 weeks and 4 months later. Confocal imaging of the hippocampus revealed a marked increase in granule cell size and an increase in dendritic spine density. The onset of morphological changes occurred earlier in neonatal mice than in young adults. We used whole-cell recordings from granule cells in acute slices to assess synaptic function after Pten knockdown. Consistent with the increase in dendritic spines, the frequency of excitatory miniature and spontaneous postsynaptic currents increased. However, there was little or no effect on IPSCs. Thus, Pten knockdown results in an imbalance between excitatory and inhibitory synaptic activity. Because reductions in Pten affected mature granule cells as well as developing granule cells, we suggest that the disruption of circuit function by Pten hypofunction may be ongoing well beyond early development. Copyright © 2011 the authors.

Cite

CITATION STYLE

APA

Luikart, B. W., Schnell, E., Washburn, E. K., Bensen, A. S. L., Tovar, K. R., & Westbrook, G. L. (2011). Pten knockdown in vivo increases excitatory drive onto dentate granule cells. Journal of Neuroscience, 31(11), 4345–4354. https://doi.org/10.1523/JNEUROSCI.0061-11.2011

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free