Pten knockdown in vivo increases excitatory drive onto dentate granule cells

Bryan W. Luikart, Eric Schnell, Eric K. Washburn, AeSoon L. Bensen, Kenneth R. Tovar, Gary Westbrook

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)4345-4354
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number11
DOIs
StatePublished - Mar 16 2011

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Dendritic Spines
Phosphoric Monoester Hydrolases
Young Adult
Hippocampus
Chromosomes, Human, Pair 10
Lentivirus
Synaptic Potentials
Patch-Clamp Techniques
Autistic Disorder
Cell Size
Small Interfering RNA
Lipids
Mutation
Injections
Drive
Autism Spectrum Disorder
Tensins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pten knockdown in vivo increases excitatory drive onto dentate granule cells. / Luikart, Bryan W.; Schnell, Eric; Washburn, Eric K.; Bensen, AeSoon L.; Tovar, Kenneth R.; Westbrook, Gary.

In: Journal of Neuroscience, Vol. 31, No. 11, 16.03.2011, p. 4345-4354.

Research output: Contribution to journalArticle

Luikart, Bryan W. ; Schnell, Eric ; Washburn, Eric K. ; Bensen, AeSoon L. ; Tovar, Kenneth R. ; Westbrook, Gary. / Pten knockdown in vivo increases excitatory drive onto dentate granule cells. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 11. pp. 4345-4354.
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