Abstract | Modulation of anxiety and fear via distinct intrahippocampal circuits

Open accessCopyright infoDownload PDFDownload figures

Modulation of anxiety and fear via distinct intrahippocampal circuits


Affiliation details

McLean Hospital, United States; Harvard Medical School, United States; The University of Tennessee Health Science Center, United States; Yale School of Medicine, United States; Russian Academy of Sciences, Russia; University of Zurich, Switzerland

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 and 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.

DOI: http://dx.doi.org/10.7554/eLife.14120.001