Striatal adenosine A 2A  receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Dysfunction of the striatum is frequently associated with sleep disturbances. However, its role in sleep-wake regulation has been paid little attention even though the striatum densely expresses adenosine A _2A receptors (A _2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A _2AR neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping and immunoelectron microscopy revealed that striatal A _2AR neurons innervated the external globus pallidus (GPe) in a topographically organized manner and preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons. Moreover, lesions of GPe PV neurons abolished the sleep-promoting effect of striatal A _2AR neurons. In addition, chemogenetic inhibition of striatal A _2AR neurons led to a significant decrease of NREM sleep at active period, but not inactive period of mice. These findings reveal a prominent contribution of striatal A _2AR neuron/GPe PV neuron circuit in sleep control.

Related collections

Most cited references 54

Record: found
Abstract: found
Article: not found

Adenosine receptors as drug targets--what are the challenges?

Bertil Fredholm, Jiang-Fan Chen, Holger Eltzschig (2013)

Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors--either directly or indirectly--have now entered the clinic. However, only one adenosine receptor-specific agent--the adenosine A2A receptor agonist regadenoson (Lexiscan; Astellas Pharma)--has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges.

0 comments Cited 143 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Physiology and pharmacology of striatal neurons.

Anatol C. Kreitzer (2008)

The basal ganglia occupy the core of the forebrain and consist of evolutionarily conserved motor nuclei that form recurrent circuits critical for motivation and motor planning. The striatum is the main input nucleus of the basal ganglia and a key neural substrate for procedural learning and memory. The vast majority of striatal neurons are spiny GABAergic projection neurons, which exhibit slow but temporally precise spiking in vivo. Contributing to this precision are several different types of interneurons that constitute only a small fraction of total neuron number but play a critical role in regulating striatal output. This review examines the cellular physiology and modulation of striatal neurons that give rise to their unique properties and function.

0 comments Cited 90 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Adenosine and sleep-wake regulation.

Robert E. Strecker, R Basheer, R W McCarley … (2004)

This review addresses three principal questions about adenosine and sleep-wake regulation: (1) Is adenosine an endogenous sleep factor? (2) Are there specific brain regions/neuroanatomical targets and receptor subtypes through which adenosine mediates sleepiness? (3) What are the molecular mechanisms by which adenosine may mediate the long-term effects of sleep loss? Data suggest that adenosine is indeed an important endogenous, homeostatic sleep factor, likely mediating the sleepiness that follows prolonged wakefulness. The cholinergic basal forebrain is reviewed in detail as an essential area for mediating the sleep-inducing effects of adenosine by inhibition of wake-promoting neurons via the A1 receptor. The A2A receptor in the subarachnoid space below the rostral forebrain may play a role in the prostaglandin D2-mediated somnogenic effects of adenosine. Recent evidence indicates that a cascade of signal transduction induced by basal forebrain adenosine A1 receptor activation in cholinergic neurons leads to increased transcription of the A1 receptor; this may play a role in mediating the longer-term effects of sleep deprivation, often called sleep debt.

0 comments Cited 76 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Rui-Xi Li

Zhi-Li Huang:

ORCID: https://orcid.org/0000-0001-9359-1150

Louis J Ptáček: Role: Reviewing Editor

Journal

Journal ID (nlm-ta): eLife

Journal ID (iso-abbrev): Elife

Journal ID (publisher-id): eLife

Title: eLife

Publisher: eLife Sciences Publications, Ltd

ISSN (Electronic): 2050-084X

Publication date (Electronic): 12 October 2017

Publication date Collection: 2017

Volume: 6

Affiliations

[1 ]deptDepartment of Pharmacology, School of Basic Medical Science Fudan University ShanghaiChina

[2 ]deptState Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science Fudan University ShanghaiChina

[3 ]deptDepartment of Anatomy, Histology and Embryology, School of Basic Medical Science Fudan University ShanghaiChina

[4 ]deptInternational Institute for Integrative Sleep Medicine University of Tsukuba TsukubaJapan

[5 ]deptLaboratory of Neurophysiology, ULB Neuroscience Institute Université Libre de Bruxelles BrusselsBelgium

University of California, San Francisco United States

Author notes

[†]

These authors contributed equally to this work.

Article

Publisher ID: 29055

DOI: 10.7554/eLife.29055

PMC ID: 5655138

PubMed ID: 29022877

License:

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.