Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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Detail(s)
Original language | English |
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Pages (from-to) | 1325–1338 |
Journal / Publication | Neuroscience Bulletin |
Volume | 37 |
Issue number | 9 |
Online published | 18 Jun 2021 |
Publication status | Published - Sept 2021 |
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DOI | DOI |
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85108239197&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(c436c9d1-67b5-4b66-8e67-d7782992e84c).html |
Abstract
A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-NTM) mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze (EPM) and showed reduced social preference in a three-chamber social interaction test. Following EPM tests, c-Fos expression levels indicated that the nucleus accumbens (NAc) was associated with risk-avoidance behavior in DISC1-NTM mice. In addition, in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons (FS) in the NAc were significantly lower in DISC1-NTM mice than in wild-type (WT) mice. In addition, in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin (PV) neurons in the NAc of DISC1-NTM mice than in WT controls. The impairment of risk avoidance in DISC1-NTM mice was rescued using optogenetic tools that activated NAcPV neurons. Finally, inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-NTM mice during tests on the elevated zero maze. Taken together, our findings confirm an impairment in risk avoidance in DISC1-NTM mice and suggest that reduced excitability of NAcPV neurons is responsible.
Research Area(s)
- DISC1, Nucleus accumbens, Parvalbumin, Risk avoidance
Citation Format(s)
Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice. / Zhou, Xinyi; Wu, Bifeng; Liu, Wenhao et al.
In: Neuroscience Bulletin, Vol. 37, No. 9, 09.2021, p. 1325–1338.
In: Neuroscience Bulletin, Vol. 37, No. 9, 09.2021, p. 1325–1338.
Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review
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