Journal
CEREBRAL CORTEX
Volume 26, Issue 5, Pages 2325-2340Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhw001
Keywords
contextual fear memory; hippocampus; interneurons; memory extinction; parvalbumin; sharp wave ripples
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Funding
- Bundesministerium fur Bildung and Forschung BMBF (Era-Net NEURON II CIPRESS)
- Helmholtz Association [VH-NG-246]
- excellence cluster NeuroCure
- Deutsche Forschungsgemeinschaft DFG [SFB-TR3 TPB5, SFB779 TPB5, SPP 1784 ME2075/7-1, He1128/16-1]
- German Israeli Project Cooperation
- German Research Foundation (DIP) project
- Hertie Foundation
- Technical University Braunschweig, Germany
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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 intemeurons 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 alpha 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.
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