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Identification of parvalbumin interneurons as cellular substrate of fear memory persistence

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Item Type:Article
Title:Identification of parvalbumin interneurons as cellular substrate of fear memory persistence
Creators Name:Caliskan, G. and Mueller, I. and Semtner, M. and Winkelmann, A. and Raza, A.S. and Hollnagel, J.O. and Roesler, A. and Heinemann, U. and Stork, O. and Meier, J.C.
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 {beta}3L(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.
Keywords:Contextual Fear Memory, Hippocampus, Interneurons, Memory Extinction, Parvalbumin, Sharp Wave Ripples, Animals, Mice
Source:Cerebral Cortex
ISSN:1047-3211
Publisher:Oxford University Press (U.S.A.)
Volume:26
Number:5
Page Range:2325-2340
Date:May 2016
Official Publication:https://doi.org/10.1093/cercor/bhw001
PubMed:View item in PubMed

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