DREADD in parvalbumin interneurons of the dentate gyrus modulates anxiety, social interaction and memory extinction.
2016
Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory,
such as spatial working memory. However, how PV-positive interneurons in the subregions of the
hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible
activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs
(DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which
co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq
ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received
bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective
activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior
in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PVpositive
interneurons appears to impair social interaction to novelty, but has no effect on social motivation.
However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3DGq
is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of
PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear
extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is
critical for regulation of the anxiety, social interaction and fear extinction. These results improve our
fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
58
References
65
Citations
NaN
KQI