Journal article
Cannabinoid receptor 1-expressing neurons in the nucleus accumbens
Proceedings of the National Academy of Sciences - PNAS, Vol.109(40), pp.E2717-E2725
PNAS Plus
10/02/2012
Handle:
https://hdl.handle.net/2376/105690
PMCID: PMC3479600
PMID: 23012412
Abstract
Endocannabinoid signaling critically regulates emotional and motivational states via activation of cannabinoid receptor 1 (CB1) in the brain. The nucleus accumbens (NAc) functions to gate emotional and motivational responses. Although expression of CB1 in the NAc is low, manipulation of CB1 signaling within the NAc triggers robust emotional/motivational alterations related to drug addiction and other psychiatric disorders, and these effects cannot be exclusively attributed to CB1 located at afferents to the NAc. Rather, CB1-expressing neurons in the NAc, although sparse, appear to be critical for emotional and motivational responses. However, the cellular properties of these neurons remain largely unknown. Here, we generated a knock-in mouse line in which CB1-expressing neurons expressed the fluorescent protein td-Tomato (tdT). Using these mice, we demonstrated that tdT-positive neurons within the NAc were exclusively fast-spiking interneurons (FSIs). These FSIs were electrically coupled with each other, and thus may help synchronize populations/ensembles of NAc neurons. CB1-expressing FSIs also form GABAergic synapses on adjacent medium spiny neurons (MSNs), providing feed-forward inhibition of NAc output. Furthermore, the membrane excitability of tdT-positive FSIs in the NAc was up-regulated after withdrawal from cocaine exposure, an effect that might increase FSI-to-MSN inhibition. Taken together with our previous findings that the membrane excitability of NAc MSNs is decreased during cocaine withdrawal, the present findings suggest that the basal functional output of the NAc is inhibited during cocaine withdrawal by multiple mechanisms. As such, CB1-expressing FSIs are targeted by cocaine exposure to influence the overall functional output of the NAc.
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Details
- Title
- Cannabinoid receptor 1-expressing neurons in the nucleus accumbens
- Creators
- Bradley D Winters - Program in NeuroscienceJuliane M Krüger - Molecular NeurobiologyXiaojie Huang - Molecular NeurobiologyZachary R Gallaher - Program in NeuroscienceMasago Ishikawa - Departments ofKrzysztof Czaja - Program in NeuroscienceJames M Krueger - Program in NeuroscienceYanhua H Huang - Program in NeuroscienceOliver M Schlüter - Molecular NeurobiologyYan Dong - Program in Neuroscience
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.109(40), pp.E2717-E2725
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Series
- PNAS Plus
- Publisher
- National Academy of Sciences
- Identifiers
- 99900547064301842
- Language
- English
- Resource Type
- Journal article