A sensitive period for GABAergic interneurons in the dentate gyrus in modulating sensorimotor gating

Nannan Guo, Kaichi Yoshizaki, Ryuichi Kimura, Fumikazu Suto, Yuchio Yanagawa, Noriko Osumi

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34 Citations (Scopus)


Developmental perturbations during adolescence have been hypothesized to be a risk factor for the onset of several neuro psychiatric diseases. However the physiological alterations that result from such insults are incompletely understood. We investigated whether a defined perturbation during adolescence affected hippocampus-dependent sensorimotor gating functions, a proposed endophenotype in several psychiatric diseases, most notably schizophrenia. The developmental perturbation was induced during adolescence in mice using an antimitotic agent, methyl azoxymethanol acetate (MAM), during postnatal weeks (PW) 4-6. MAM-treated mice showed a decrease in hippocampal neurogenesis immediately after treatment, which was restored by PW10 in adulthood. However, the mice treated with MAM during adolescent stages exhibited a persistent sensorimotor gating deficiency and are duction in prepulse inhibition-related activation of hippocampal and prefrontal neurons in adulthood. Cellular analyses found a reduction of GABAergic inhibitory neurons and abnormal dendritic morphology of immature neurons in the dentate gyrus (DG). Interestingly, bilateral infusion of muscimol, a GABAAreceptor agonist, into the DG region reversed the prepulse inhibition abnormality in MAM-treated mice. Furthermore, the behavioral deficits together with the decrease in the number of GABAergic neurons in this MAM model were rescued by exposure to an enriched environment during a defined critical adolescent period.These observations suggest a possible role for GABAergicinterneurons in the DG during adolescence. This role may be related to the establishment of neural circuitry required for sensorimotor gating. It is plausible that changes in neuro genesis during this window may affect the survival of GABAergicinterneurons, although this link needs to be causally addressed.

Original languageEnglish
Pages (from-to)6691-6704
Number of pages14
JournalJournal of Neuroscience
Issue number15
Publication statusPublished - 2013 Apr 10


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