p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli
| Autor: | Naoki Sotogaku, Yukie Kawahara, Yuuki Hanada, Paul Greengard, Akinori Nishi, Yoshinori N. Ohnishi, Mahomi Kuroiwa, Yotam Sagi, Takahide Shuto |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
p11
Dopamine Cholinergic Agents Pharmacology Nucleus accumbens Nucleus Accumbens cholinergic interneuron Cocaine Reward Interneurons Muscarinic acetylcholine receptor medicine Animals Cholinergic neuron Feature: Research Highlights Mice Knockout Chemistry General Neuroscience Dopaminergic 3.1 General Medicine New Research Receptors Muscarinic Acetylcholine Cholinergic Neurons anhedonia Nicotinic agonist Cholinergic Disorders of the Nervous System medicine.drug |
| Zdroj: | eNeuro |
| ISSN: | 2373-2822 |
| Popis: | Visual Abstract A recent study showed that p11 expressed in cholinergic interneurons (CINs) of the nucleus accumbens (NAc) is a key regulator of depression-like behaviors. Dopaminergic neurons projecting to the NAc are responsible for reward-related behaviors, and their function is impaired in depression. The present study investigated the role of p11 in NAc CINs in dopamine responses to rewarding stimuli. The extracellular dopamine and acetylcholine (ACh) levels in the NAc were determined in freely moving male mice using in vivo microdialysis. Rewarding stimuli (cocaine, palatable food, and female mouse encounter) induced an increase in dopamine efflux in the NAc of wild-type (WT) mice. The dopamine responses were attenuated (cocaine) or abolished (food and female mouse encounter) in constitutive p11 knock-out (KO) mice. The dopamine response to cocaine was accompanied by an increase in ACh NAc efflux, whereas the attenuated dopamine response to cocaine in p11 KO mice was restored by activation of nicotinic or muscarinic ACh receptors in the NAc. Dopamine responses to rewarding stimuli and ACh release in the NAc were attenuated in mice with deletion of p11 from cholinergic neurons (ChAT-p11 cKO mice), whereas gene delivery of p11 to CINs restored the dopamine responses. Furthermore, chemogenetic studies revealed that p11 is required for activation of CINs in response to rewarding stimuli. Thus, p11 in NAc CINs plays a critical role in activating these neurons to mediate dopamine responses to rewarding stimuli. The dysregulation of mesolimbic dopamine system by dysfunction of p11 in NAc CINs may be involved in pathogenesis of depressive states. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|