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Neuropsychopharmacology. 2014 Jul;39(8):1880-92. doi: 10.1038/npp.2014.35. Epub 2014 Feb 14.

Chemogenetic inactivation of ventral hippocampal glutamatergic neurons disrupts consolidation of contextual fear memory.

Author information

1
Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
2
1] Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA [2] Department of Pharmacology, Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
3
1] Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA [2] Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
4
1] Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA [2] Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC, USA [3] Program in Neuroscience, University of North Carolina, Chapel Hill, NC, USA [4] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA [5] Division of Chemical Biology and Medicinal Chemistry, School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA [6] NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, NC, USA.

Abstract

Synaptic consolidation is a process thought to consolidate memory in the brain. Although lesion studies have mainly implicated the hippocampus (HPC) in this process, it is unknown which cell type(s) or regions of the HPC might be essential for synaptic consolidation. To selectively and reversibly suppress hippocampal neuronal activity during this process, we developed a new Gi-DREADD (hM4Di) transgenic mouse for in vivo manipulation of neuronal activity in freely moving animals. We found that CA1 pyramidal neurons could be dose-dependently inactivated by clozapine-n-oxide (CNO). Inactivation of hippocampal neurons within 6 h immediately after conditioned fear training successfully impaired the consolidation of contextual memory, without disturbing cued memory. To anatomically define the brain subregion critical for the behavioral effects, hM4Di viral vectors were transduced and selectively expressed in the glutamatergic neurons in either the dorsal or ventral HPC. Significantly, we found that selective inactivation of ventral but not dorsal glutamatergic hippocampal neurons suppressed the synaptic consolidation of contextual memory.

PMID:
24525710
PMCID:
PMC4059896
DOI:
10.1038/npp.2014.35
[Indexed for MEDLINE]
Free PMC Article
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