title: 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.
authors.affiliation: Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, United States.|Department of Psychiatry, Harvard Medical School, Boston, United States.
authors.forename: Elif
authors.identifier: http://orcid.org/0000-0002-1804-6811
authors.initials: E
authors.lastname: Engin
authors.affiliation: Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, United States.|Department of Psychiatry, Harvard Medical School, Boston, United States.
authors.forename: Kiersten S
authors.initials: KS
authors.lastname: Smith
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, United States.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Section of Comparative Medicine, Yale School of Medicine, New Haven, United States.
authors.forename: David
authors.initials: D
authors.lastname: Nagy
authors.affiliation: Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, United States.|Department of Psychiatry, Harvard Medical School, Boston, United States.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Foster
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, United States.|Cellular Neurobiology Laboratory, McLean Hospital, Belmont, United States.|Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Tsvetkov
authors.affiliation: Institute for Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Keist
authors.affiliation: Institute for Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Crestani
authors.affiliation: Institute for Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Fritschy
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, United States.|Cellular Neurobiology Laboratory, McLean Hospital, Belmont, United States.
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Bolshakov
authors.affiliation: Section of Comparative Medicine, Yale School of Medicine, New Haven, United States.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Hajos
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Heldt
authors.affiliation: Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, United States.|Department of Psychiatry, Harvard Medical School, Boston, United States.
authors.forename: Uwe
authors.initials: U
authors.lastname: Rudolph
mesh_terms: D000818:Animals; D001007:Anxiety; D001931:Brain Mapping; D005239:Fear; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D009415:Nerve Net; D011963:Receptors, GABA-A / Q000235:genetics
chemical_list: D011963:Receptors, GABA-A
keywords: GABAA receptor; anxiety; diazepam; fear; hippocampus; mouse; neuroscience; theta oscillations