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 Heldt, Uwe Rudolph

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere14120
JournaleLife
Volume5
Issue numberMARCH2016
DOIs
StatePublished - Mar 14 2016

Fingerprint

GABA-A Receptors
Neurons
Fear
Anxiety
Modulation
Networks (circuits)
Diazepam
Mountings
Brain
Cells
Pyramidal Cells
Dentate Gyrus
Hippocampus
Research
Population
Inhibition (Psychology)

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Engin, E., Smith, K. S., Gao, Y., Nagy, D., Foster, R. A., Tsvetkov, E., ... Rudolph, U. (2016). Modulation of anxiety and fear via distinct intrahippocampal circuits. eLife, 5(MARCH2016), [e14120]. https://doi.org/10.7554/eLife.14120.001

Modulation of anxiety and fear via distinct intrahippocampal circuits. / Engin, Elif; Smith, Kiersten S.; Gao, Yudong; Nagy, David; Foster, Rachel A.; Tsvetkov, Evgeny; Keist, Ruth; Crestani, Florence; Fritschy, Jean Marc; Bolshakov, Vadim Y.; Hajos, Mihaly; Heldt, Scott; Rudolph, Uwe.

In: eLife, Vol. 5, No. MARCH2016, e14120, 14.03.2016.

Research output: Contribution to journalArticle

Engin, E, Smith, KS, Gao, Y, Nagy, D, Foster, RA, Tsvetkov, E, Keist, R, Crestani, F, Fritschy, JM, Bolshakov, VY, Hajos, M, Heldt, S & Rudolph, U 2016, 'Modulation of anxiety and fear via distinct intrahippocampal circuits', eLife, vol. 5, no. MARCH2016, e14120. https://doi.org/10.7554/eLife.14120.001
Engin E, Smith KS, Gao Y, Nagy D, Foster RA, Tsvetkov E et al. Modulation of anxiety and fear via distinct intrahippocampal circuits. eLife. 2016 Mar 14;5(MARCH2016). e14120. https://doi.org/10.7554/eLife.14120.001
Engin, Elif ; Smith, Kiersten S. ; Gao, Yudong ; Nagy, David ; Foster, Rachel A. ; Tsvetkov, Evgeny ; Keist, Ruth ; Crestani, Florence ; Fritschy, Jean Marc ; Bolshakov, Vadim Y. ; Hajos, Mihaly ; Heldt, Scott ; Rudolph, Uwe. / Modulation of anxiety and fear via distinct intrahippocampal circuits. In: eLife. 2016 ; Vol. 5, No. MARCH2016.
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