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Journal of Neurodevelopmental Disorders

, Volume 1, Issue 3, pp 224–236

First Online: 11 July 2009Received: 14 February 2009Accepted: 23 June 2009

Abstract

The inhibitory GABAergic system has been implicated in multiple neuropsychiatric diseases such as schizophrenia and autism. The Dlx homeobox transcription factor family is essential for development and function of GABAergic interneurons. Mice lacking the Dlx1 gene have postnatal subtype-specific loss of interneurons and reduced IPSCs in their cortex and hippocampus. To ascertain consequences of these changes in the GABAergic system, we performed a battery of behavioral assays on the Dlx1 mutant mice, including zero maze, open field, locomotor activity, food intake, rotarod, tail suspension, fear conditioning assays context and trace, prepulse inhibition, and working memory related tasks spontaneous alteration task and spatial working memory task. Dlx1 mutant mice displayed elevated activity levels in open field, locomotor activity, and tail suspension tests. These mice also showed deficits in contextual and trace fear conditioning, and possibly in prepulse inhibition. Their learning deficits were not global, as the mutant mice did not differ from the wild-type controls in tests of working memory. Our findings demonstrate a critical role for the Dlx1 gene, and likely the subclasses of interneurons that are affected by the lack of this gene, in behavioral inhibition and associative fear learning. These observations support the involvement of particular components of the GABAergic system in specific behavioral phenotypes related to complex neuropsychiatric diseases.

KeywordsBehavior Fear conditioning Associative learning Prepulse inhibition Hyperactivity Interneuron Inhibitory GABAergic Calretinin Neuropsychiatric disease AbbreviationsITIinter-trial interval

CSconditioned stimulus

USunconditioned stimulus

SPLsound pressure level

PFCprefrontal cortex

mPFCmedial prefrontal cortices

DHdorsal hippocampus

VHventral hippocampus

Electronic supplementary materialThe online version of this article doi:10.1007-s11689-009-9025-8 contains supplementary material, which is available to authorized users.

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Autor: Rong Mao - Damon T. Page - Irina Merzlyak - Carol Kim - Laurence H. Tecott - Patricia H. Janak - John L. R. Rubenstein

Fuente: https://link.springer.com/







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