scholarly journals Sleep and Motor Control by a Basal Ganglia Circuit

2018 ◽  
Author(s):  
Danqian Liu ◽  
Chenyan Ma ◽  
Weitong Zheng ◽  
Yuanyuan Yao ◽  
Yang Dan

AbstractFrom invertebrates to humans, a defining feature of sleep is behavioral immobility(Campbell and Tobler, 1984; Hendricks et al., 2000; Shaw et al., 2000). In mammals, diminished electromyographic (EMG) activity is a major criterion for both rapid eye movement (REM) and non-REM (NREM) sleep. However, the relationship between sleep and motor control at the neuronal level remains poorly understood. Here we show that regions of the basal ganglia long known to be essential for motor suppression also play a key role in sleep generation. Optogenetic or chemogenetic activation of GABAergic neurons in mouse substantia nigra pars reticulata (SNr) strongly increased both REM and NREM sleep, whereas their inactivation suppressed sleep and increased wakefulness. Analysis of natural home-cage behavior showed that mice transition sequentially through several behavioral states: locomotion, non-locomotor movement, quiet wakefulness, and sleep. Activation/inactivation of SNr neurons promoted/suppressed sleep by biasing the direction of progression through the natural behavioral sequence. Virus-mediated circuit tracing showed that SNr GABAergic neurons project to multiple wake-promoting monoaminergic cell groups in addition to the thalamus and mesencephalic locomotor region, and activating each projection promoted sleep. Within the thalamus, direct optogenetic inactivation of glutamatergic neurons is sufficient to enhance sleep, but the effect is largely restricted to the regions receiving SNr projection. Furthermore, a major source of excitatory inputs to the SNr is the subthalamic nucleus (STN), and activation of neurotensin-expressing glutamatergic neurons in the STN also promoted sleep. Together, these results demonstrate a key role of the STN-SNr basal ganglia pathway in sleep generation and reveal a novel circuit mechanism linking sleep and motor control.

2020 ◽  
Author(s):  
Anes Ju ◽  
Beatriz Fernandez-Arroyo ◽  
Yifan Wu ◽  
Débora Jacky ◽  
Anna Beyeler

Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75-80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73-82%). These observations suggest that most glutamatergic neurons can respond to 5‑HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Anes Ju ◽  
Beatriz Fernandez-Arroyo ◽  
Yifan Wu ◽  
Débora Jacky ◽  
Anna Beyeler

Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5-HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potentials within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5-HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5-HT1A or 5-HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5-HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75–80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73–82%). These observations suggest that most glutamatergic neurons can respond to 5-HT through 5-HT1A or 5-HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.


Author(s):  
Adriane Guillaumin ◽  
Gian Pietro Serra ◽  
François Georges ◽  
Åsa Wallén-Mackenzie

AbstractThe subthalamic nucleus is important achieve intended movements. Loss of its normal function is strongly associated with several movement disorders. Classical basal ganglia models postulate that two parallel pathways, the direct and indirect pathways, exert opposing control over movement, with the subthalamic nucleus part of the indirect pathway through which competing motor programs are prevented. The subthalamic nucleus is regulated by both inhibitory and excitatory projections but experimental evidence for its role in motor control has remained sparse. The objective here was to tease out the selective impact of the subthalamic nucleus on several motor parameters required to achieve intended movement, including locomotion, balance and motor coordination. Optogenetic excitation and inhibition using both bilateral and unilateral stimulations of the subthalamic nucleus were implemented in freely-moving mice. The results demonstrate that selective optogenetic inhibition of the subthalamic nucleus enhances locomotion while its excitation reduces locomotion. These findings lend experimental support to basal ganglia models in terms of locomotion. However, further analysis of subthalamic nucleus excitation revealed grooming and disturbed gait. Selective excitation also caused reduced motor coordination, independent of grooming, in advanced motor tasks. This study contributes experimental evidence for a regulatory role of the subthalamic nucleus in motor control.HighlightsBilateral optogenetic excitation of the subthalamic nucleus in freely-moving mice reduces forward locomotion while optogenetic inhibition leads to its increase.Unilateral optogenetic excitation and inhibition of the subthalamic nucleus cause opposite rotational behavior.Bilateral optogenetic excitation, but not inhibition, of the subthalamic nucleus induces jumping and self-grooming behavior.Engaged in advanced motor tasks, bilateral optogenetic excitation causes mice to lose motor coordination.The results provide experimental support for predictions by the basal ganglia motor model on the role of the subthalamic nucleus in locomotion, and identifies a causal role for the subthalamic nucleus in self-grooming.


2018 ◽  
Author(s):  
Fabrice Arcizet ◽  
Richard J. Krauzlis

AbstractThe basal ganglia are important for action selection. They are also implicated in perceptual and cognitive functions that seem far removed from motor control. Here, we tested whether the role of the basal ganglia in selection extends to non-motor aspects of behavior by recording neuronal activity in the caudate nucleus while animals performed a covert spatial attention task. We found that caudate neurons strongly select the spatial location of the relevant stimulus throughout the task even in the absence of any overt action. This spatially selective activity was dependent on task and visual conditions, and could be dissociated from goal-directed actions. Caudate activity was also sufficient to correctly identify every epoch in the covert attention task. These results provide a novel perspective on mechanisms of attention by demonstrating that the basal ganglia are involved in spatial selection and tracking of behavioral states even in the absence of overt orienting movements.


Author(s):  
Lijuan Hou ◽  
Jimin Zhang ◽  
Xinwei Wang ◽  
Fei Gong ◽  
Xue Sun
Keyword(s):  

2020 ◽  
Author(s):  
Anes Ju ◽  
Beatriz Fernandez-Arroyo ◽  
Yifan Wu ◽  
Débora Jacky ◽  
Anna Beyeler

Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75-80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73-82%). These observations suggest that most glutamatergic neurons can respond to 5‑HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.


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