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Striatal adenosine A_2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus.

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.

SUBMITTER: Yuan XS

PROVIDER: S-EPMC5655138 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus.

Yuan Xiang-Shan XS Wang Lu L Dong Hui H Qu Wei-Min WM Yang Su-Rong SR Cherasse Yoan Y Lazarus Michael M Schiffmann Serge N SN d'Exaerde Alban de Kerchove AK Li Rui-Xi RX Huang Zhi-Li ZL

eLife 20171012

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 A2A receptors (A2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A2AR neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping an ...[more]

PMID: 29022877

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Project description:Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction.Significance statementUntil recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the markers parvalbumin and Npas1. Our study provides evidence that parvalbumin and Npas1 neurons have different topologies within the basal ganglia.

Dataset Information

Striatal adenosine A_2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus.

Publications

Striatal adenosine A<sub>2A</sub> receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus.

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