title: Identification of Parvalbumin Interneurons as Cellular Substrate of Fear Memory Persistence.
abstract: Parvalbumin-positive (PV) basket cells provide perisomatic inhibition in the cortex and hippocampus and control generation of memory-related network activity patterns, such as sharp wave ripples (SPW-R). Deterioration of this class of fast-spiking interneurons has been observed in neuropsychiatric disorders and evidence from animal models suggests their involvement in the acquisition and extinction of fear memories. Here, we used mice with neuron type-targeted expression of the presynaptic gain-of-function glycine receptor RNA variant GlyR α3L(185L)to genetically enhance the network activity of PV interneurons. These mice showed reduced extinction of contextual fear memory but normal auditory cued fear memory. They furthermore displayed increase of SPW-R activity in area CA3 and CA1 and facilitated propagation of this particular network activity pattern, as determined in ventral hippocampal slice preparations. Individual freezing levels during extinction and SPW-R propagation were correlated across genotypes. The same was true for parvalbumin immunoreactivity in the ventral hippocampus, which was generally augmented in the GlyR mutant mice and correlated with individual freezing levels. Together, these results identify PV interneurons as critical cellular substrate of fear memory persistence and associated SPW-R activity in the hippocampus. Our findings may be relevant for the identification and characterization of physiological correlates for posttraumatic stress and anxiety disorders.
authors.affiliation: Institute for Neurophysiology, Charité Universitätsmedizin Berlin, Berlin 14195, Germany.|Institute of Biology, Department of Genetics and Molecular Neurobiology, Otto-von-Guericke-University, Magdeburg 39120, Germany.
authors.forename: Gürsel
authors.initials: G
authors.lastname: Çaliskan
authors.affiliation: Institute of Biology, Department of Genetics and Molecular Neurobiology, Otto-von-Guericke-University, Magdeburg39120, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Müller
authors.affiliation: Division Cell Physiology, Zoological Institute, Braunschweig38106, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Semtner
authors.affiliation: Division Cell Physiology, Zoological Institute, Braunschweig 38106, Germany.|RNA editing and Hyperexcitability Disorders Helmholtz Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Winkelmann
authors.affiliation: Institute of Biology, Department of Genetics and Molecular Neurobiology, Otto-von-Guericke-University, Magdeburg39120, Germany.
authors.forename: Ahsan S
authors.initials: AS
authors.lastname: Raza
authors.affiliation: Institute for Neurophysiology, Charité Universitätsmedizin Berlin, Berlin 14195, Germany.|Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Hollnagel
authors.affiliation: Institute for Neurophysiology, Charité Universitätsmedizin Berlin, Berlin14195, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Rösler
authors.affiliation: Institute for Neurophysiology, Charité Universitätsmedizin Berlin, Berlin14195, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Heinemann
authors.affiliation: Institute of Biology, Department of Genetics and Molecular Neurobiology, Otto-von-Guericke-University, Magdeburg 39120, Germany.|Center for Behavioral Brain Sciences, Magdeburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stork
authors.affiliation: Division Cell Physiology, Zoological Institute, Braunschweig 38106, Germany.|RNA editing and Hyperexcitability Disorders Helmholtz Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany.
authors.forename: Jochen C
authors.initials: JC
authors.lastname: Meier
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D003214:Conditioning, Classical; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010320:Parvalbumins / Q000378:metabolism*
chemical_list: D010320:Parvalbumins
keywords: contextual fear memory; hippocampus; interneurons; memory extinction; parvalbumin; sharp wave ripples