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Proc Natl Acad Sci U S A. 2016 Jun 7;113(23):6550-5. doi: 10.1073/pnas.1605019113. Epub 2016 May 20.

Medial septal GABAergic projection neurons promote object exploration behavior and type 2 theta rhythm.

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Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-308, Korea;
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095-6948;
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-930, Korea;
Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan;
Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan;
Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 136-791, Korea;
Graduate School of New Drug Discovery & Development, Chungnam National University, Daejeon 305-764, Korea;
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-308, Korea;


Exploratory drive is one of the most fundamental emotions, of all organisms, that are evoked by novelty stimulation. Exploratory behavior plays a fundamental role in motivation, learning, and well-being of organisms. Diverse exploratory behaviors have been described, although their heterogeneity is not certain because of the lack of solid experimental evidence for their distinction. Here we present results demonstrating that different neural mechanisms underlie different exploratory behaviors. Localized Cav3.1 knockdown in the medial septum (MS) selectively enhanced object exploration, whereas the null mutant (KO) mice showed enhanced-object exploration as well as open-field exploration. In MS knockdown mice, only type 2 hippocampal theta rhythm was enhanced, whereas both type 1 and type 2 theta rhythm were enhanced in KO mice. This selective effect was accompanied by markedly increased excitability of septo-hippocampal GABAergic projection neurons in the MS lacking T-type Ca(2+) channels. Furthermore, optogenetic activation of the septo-hippocampal GABAergic pathway in WT mice also selectively enhanced object exploration behavior and type 2 theta rhythm, whereas inhibition of the same pathway decreased the behavior and the rhythm. These findings define object exploration distinguished from open-field exploration and reveal a critical role of T-type Ca(2+) channels in the medial septal GABAergic projection neurons in this behavior.


Cav3.1 T-type Ca2+ channel; exploratory behaviors; hippocampal theta rhythm; medial septum; septo-hippocampal GABAergic neurons

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