A common hub for sleep and motor control in the substantia nigra

Science ◽  
2020 ◽  
Vol 367 (6476) ◽  
pp. 440-445 ◽  
Author(s):  
Danqian Liu ◽  
Weifu Li ◽  
Chenyan Ma ◽  
Weitong Zheng ◽  
Yuanyuan Yao ◽  
...  

The arousal state of the brain covaries with the motor state of the animal. How these state changes are coordinated remains unclear. We discovered that sleep–wake brain states and motor behaviors are coregulated by shared neurons in the substantia nigra pars reticulata (SNr). Analysis of mouse home-cage behavior identified four states with different levels of brain arousal and motor activity: locomotion, nonlocomotor movement, quiet wakefulness, and sleep; transitions occurred not randomly but primarily between neighboring states. The glutamic acid decarboxylase 2 but not the parvalbumin subset of SNr γ-aminobutyric acid (GABA)–releasing (GABAergic) neurons was preferentially active in states of low motor activity and arousal. Their activation or inactivation biased the direction of natural behavioral transitions and promoted or suppressed sleep, respectively. These GABAergic neurons integrate wide-ranging inputs and innervate multiple arousal-promoting and motor-control circuits through extensive collateral projections.

Author(s):  
Wolfgang L�scher ◽  
Ulrich Ebert ◽  
Holger Lehmann ◽  
Christoph Rosenthal ◽  
Guido Nikkhah

2015 ◽  
Vol 114 (4) ◽  
pp. 2500-2508 ◽  
Author(s):  
L. Sosulina ◽  
C. Strippel ◽  
H. Romo-Parra ◽  
A. L. Walter ◽  
T. Kanyshkova ◽  
...  

Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior. Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE). Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl). In GFP-positive neurons within CEl, SP caused a membrane depolarization and increase in input resistance, associated with an increase in action potential firing frequency. Under voltage-clamp conditions, the SP-specific membrane current reversed at −101.5 ± 2.8 mV and displayed inwardly rectifying properties indicative of a membrane K+ conductance. Moreover, SP responses were blocked by the neurokinin type 1 receptor (NK1R) antagonist L-822429 and mimicked by the NK1R agonist [Sar9,Met(O2)11]-SP. Immunofluorescence staining confirmed localization of NK1R in GFP-positive neurons in CEl, predominantly in PKCδ-negative neurons (80%) and in few PKCδ-positive neurons (17%). Differences in SP responses were not observed between the major types of CEl neurons (late firing, regular spiking, low-threshold bursting). In addition, SP increased the frequency and amplitude of GABAergic synaptic events in CEl neurons depending on upstream spike activity. These data indicate a NK1R-mediated increase in excitability and GABAergic activity in CEl neurons, which seems to mostly involve the PKCδ-negative subpopulation. This influence can be assumed to increase reciprocal interactions between CElon and CEloff pathways, thereby boosting the medial CE (CEm) output pathway and contributing to the anxiogenic-like action of SP in the amygdala.


2000 ◽  
Vol 12 (1) ◽  
pp. 78-97 ◽  
Author(s):  
E. P. Loeb ◽  
S. F. Giszter ◽  
P. Saltiel and E. Bizzi ◽  
F. A. Mussa-Ivaldi

Cognitive approaches to motor control typically concern sequences of discrete actions without taking into account the stunning complexity of the geometry and dynamics of the muscles. This begs the question: Does the brain convert the intricate, continuous-time dynamics of the muscles into simpler discrete units of actions, and if so, how? One way for the brain to form discrete units of behavior from muscles is through the synergistic co-activation of muscles. While this possibility has long been known, the composition of potential muscle synergies has remained elusive. In this paper, we have focused on a method that allowed us to examine and compare the limb stabilization properties of all possible muscle combinations. We found that a small set (as few as 23 out of 65,536) of all possible combinations of 16 limb muscles are robust with respect to activation noise: these muscle combinations could stabilize the limb at predictable, restricted portions of the workspace in spite of broad variations in the force output of their component muscles. The locations at which the robust synergies stabilize the limb are not uniformly distributed throughout the leg's workspace, but rather, they cluster at four workspace areas. The simulated robust synergies are similar to the actual synergies we have previously found to be generated by activation of the spinal cord. Thus, we have developed a new analytical method that enabled us to select a few muscle synergies with interesting properties out of the set of possible muscle combinations. Beyond this, the identification of robustness as a common property of the synergies in simple motor behaviors will open the way to the study of dynamic stability, which is an important and distinct property of the vertebrate motor-control system.


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