Journal
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
Volume 1, Issue 3, Pages 224-236Publisher
BIOMED CENTRAL LTD
DOI: 10.1007/s11689-009-9025-8
Keywords
Behavior; Fear conditioning; Associative learning; Prepulse inhibition; Hyperactivity; Interneuron; Inhibitory; GABAergic; Calretinin; Neuropsychiatric disease
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Funding
- Simons Foundation
- Autism Consortium
- National Eye Institute Kirschstein-NRSA Fellowship [1 F32 EY017243]
- Nancy Lurie Marks Family Foundation
- state of California
- Nina Ireland
- NIMH R37 [MH049428]
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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 wildtype 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.
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