Modulation of anxiety and fear via distinct intrahippocampal circuits

Elif Engin, Kiersten S. Smith, Yudong Gao, David Nagy, Rachel A. Foster, Evgeny Tsvetkov, Ruth Keist, Florence Crestani, Jean Marc Fritschy, Vadim Y. Bolshakov, Mihaly Hajos, Scott A. Heldt, Uwe Rudolph

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere14120
Issue numberMARCH2016
StatePublished - Mar 14 2016
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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