Modulation of anxiety and fear via distinct intrahippocampal circuits.

Abstract:

: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 α2 subunit, we demonstrate that inhibition of the principal neurons of the dentate gyrus or CA3 via α2-containing GABAA receptors (α2GABAARs) 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.

journal_name

Elife

journal_title

eLife

authors

Engin E,Smith KS,Gao Y,Nagy D,Foster RA,Tsvetkov E,Keist R,Crestani F,Fritschy JM,Bolshakov VY,Hajos M,Heldt SA,Rudolph U

doi

10.7554/eLife.14120

subject

Has Abstract

pub_date

2016-03-14 00:00:00

pages

e14120

issn

2050-084X

journal_volume

5

pub_type

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