Pten loss results in inappropriate excitatory connectivity.

Autor: Skelton PD; Department of Molecular and Systems Biology, Dartmouth Geisel School of Medicine, Hanover, NH, 03755, USA., Frazel PW; Department of Molecular and Systems Biology, Dartmouth Geisel School of Medicine, Hanover, NH, 03755, USA., Lee D; Department of Neurosciences, Cleveland Clinic, Cleveland, OH, 44195, USA., Suh H; Department of Neurosciences, Cleveland Clinic, Cleveland, OH, 44195, USA., Luikart BW; Department of Molecular and Systems Biology, Dartmouth Geisel School of Medicine, Hanover, NH, 03755, USA. Bryan.W.Luikart@Dartmouth.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2019 Nov; Vol. 24 (11), pp. 1627-1640. Date of Electronic Publication: 2019 Apr 09.
DOI: 10.1038/s41380-019-0412-6
Abstrakt: Pten mutations are associated with autism spectrum disorder. Pten loss of function in neurons increases excitatory synaptic connectivity, contributing to an imbalance between excitation and inhibition. We aimed to determine whether Pten loss results in aberrant connectivity in neural circuits. We compared postnatally generated wild-type and Pten knockout granule neurons integrating into the dentate gyrus using a variety of methods to examine their connectivity. We found that postsynaptic Pten loss provides an advantage to dendritic spines in competition over a limited pool of presynaptic boutons. Retrograde monosynaptic tracing with rabies virus reveals that this results in synaptic contact with more presynaptic partners. Using independently excitable opsins to interrogate multiple inputs onto a single neuron, we found that excess connectivity is established indiscriminately from among glutamatergic afferents. Therefore, Pten loss results in inappropriate connectivity whereby neurons are coupled to a greater number of synaptic partners.
Databáze: MEDLINE
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