Locomotion is regulated by distributed circuits and achieved by the concerted activation of body musculature. While the basic properties of executive circuits in the spinal cord are fairly well understood, the precise mechanisms by which the brain impacts locomotion are much less clear. This Review discusses recent work unraveling the cellular identity, connectivity, and function of supraspinal circuits. We focus on their involvement in the regulation of the different phases of locomotion and their interaction with spinal circuits. Dedicated neuronal populations in the brainstem carry locomotor instructions, including initiation, speed, and termination. To align locomotion with behavioral needs, brainstem output structures are recruited by midbrain and forebrain circuits that compute and infer volitional, innate, and context-dependent locomotor properties. We conclude that the emerging logic of supraspinal circuit organization helps to understand how locomotor programs from exploration to hunting and escape are regulated by the brain.

Summary The mesencephalic locomotor region (MLR) is a key midbrain center with roles in locomotion. Despite extensive studies and clinical trials aimed at therapy-resistant Parkinson’s disease (PD), debate on its function remains. Here, we reveal the existence of functionally diverse neuronal populations with distinct roles in control of body movements. We identify two spatially intermingled glutamatergic populations separable by axonal projections, mouse genetics, neuronal activity profiles, and motor functions. Most spinally projecting MLR neurons encoded the full-body behavior rearing. Loss- and gain-of-function optogenetic perturbation experiments establish a function for these neurons in controlling body extension. In contrast, Rbp4-transgene-positive MLR neurons project in an ascending direction to basal ganglia, preferentially encode the forelimb behaviors handling and grooming, and exhibit a role in modulating movement. Thus, the MLR contains glutamatergic neuronal subpopulations stratified by projection target exhibiting roles in action control not restricted to locomotion.

Background: In addition to insulin-sensitizing effects, adiponectin influences several mechanisms involved in pulmonary arterial hypertension (PAH) pathobiology. Insulin resistance has been associated with PAH, and elevated adiponectin levels have been described in left heart failure (HF) as a response to the increased metabolic stress. No studies have been performed in right HF or PAH patients. Hypothesis: Compared to healthy controls, PAH patients have a different plasma adipocytokine profile, higher insulin resistance, and higher inflammatory systemic activation. Methods: A case-control study was conducted in PAH patients individually matched for sex, age, and body mass index. We characterized the clinical features, functional status (6-minute walking test), and hemodynamic profile of cases (n = 25). We measured insulin resistance (homeostasis model assessment and high-density lipoprotein/triglycerides ratio), inflammatory systemic activation (high-sensitivity C-reactive protein), and plasma adipocytokine profile (adiponectin, leptin, visfatin, and resistin) in cases and controls. Results: PAH patients had significantly higher adiponectin levels than controls (12.4 ± 6.9 vs 8.1 ± 4.5 μg/mL; P < 0.05) and higher high-sensitivity C-reactive protein (2.96 ± 3.2 vs 1.08 ± 1.1; P < 0.05). No statistically significant differences were found in plasma levels of leptin, visfatin, and resistin between groups. Conclusions: Adiponectin levels are increased in PAH patients compared to controls. Further studies are needed to study the potential role of adiponectin as a PAH biomarker.

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