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Publication : Modulation of anxiety and fear via distinct intrahippocampal circuits.

First Author  Engin E Year  2016
Journal  Elife Volume  5
Pages  e14120 PubMed ID  26971710
Mgi Jnum  J:231149 Mgi Id  MGI:5767015
Doi  10.7554/eLife.14120 Citation  Engin E, et al. (2016) Modulation of anxiety and fear via distinct intrahippocampal circuits. Elife 5:e14120
abstractText  Recent findings indicate a high level of specialization at the level of microcircuits and cell populations within brain structures with regards to the control of fear and anxiety. The hippocampus, however, has been treated as a unitary structure in anxiety and fear research despite mounting evidence that different hippocampal subregions have specialized roles in other cognitive domains. Using novel cell-type- and region-specific conditional knockouts of the GABAA receptor alpha2 subunit, we demonstrate that inhibition of the principal neurons of the dentate gyrus or CA3 via alpha2-containing GABAA receptors (alpha2GABAARs) is required to suppress anxiety, while the inhibition of CA1 pyramidal neurons is required to suppress fear responses. We further show that the diazepam-modulation of hippocampal theta activity shows certain parallels with our behavioral findings, suggesting a possible mechanism for the observed behavioral effects. Thus, our findings demonstrate a double dissociation in the regulation of anxiety versus fear by hippocampal microcircuitry.
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