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The connectivity patterns of neurons sustaining the functionality of spinal locomotor circuits rely on the specification of hundreds of motor neuron and interneuron subtypes precisely arrayed within the embryonic spinal cord. Knowledge acquired by developmental biologists on the molecular mechanisms underpinning this process in vivo has supported the development of 2D and 3D differentiation strategies to generate spinal neuronal diversity from mouse and human pluripotent stem cells (PSCs). Here, we review recent breakthroughs in this field and the perspectives opened up by models of in vitro embryogenesis to approach the mechanisms underlying neuronal diversification and the formation of functional mouse and human locomotor circuits. Beyond serving fundamental investigations, these new approaches should help engineering neuronal circuits differentially impacted in neuromuscular disorders, such as amyotrophic lateral sclerosis or spinal muscular atrophies, and thus open new avenues for disease modeling and drug screenings.
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http://dx.doi.org/10.1016/j.conb.2020.12.002 | DOI Listing |
Eur J Neurosci
September 2025
Department of Neuroanatomy, Yokohama City University School of Medicine, Yokohama, Japan.
Pelvic visceromotor functions such as micturition are regulated by coordinated autonomic and somatic motor pathways from the central nervous system. The parasympathetic system induces detrusor muscle contraction while the somatic system facilitates relaxation of the external urethral sphincter, ensuring synchronized and efficient bladder emptying during the voiding process. This study explores the relationship between Barrington's nucleus corticotropin-releasing hormone (CRH)-ergic projections and the formation of perineural nets (PNNs) among spinal motoneurons, particularly parasympathetic preganglionic neurons in the intermediolateral nucleus (IML) and Onuf's nucleus during the maturation of the neural circuitry controlling pelvic visceromotor functions.
View Article and Find Full Text PDFNeurobiol Dis
September 2025
Mudanjiang Collaborative Innovation Center for development and application of Northern Medicine Resources, Mudanjiang, PR China; Institute of Neural Tissue Engineering, Mudanjiang Medical University, Mudanjiang, Heilongjiang, PR China. Electronic address:
Spinal cord injury (SCI) causes irreversible motor deficits due to disrupted lumbar circuitry. However, transcriptional mechanisms in distal lumbar circuits are poorly understood. We identify POU6F1 as a critical transcriptional regulator in spinal lumbar segment (SLS, L3-L5) motor circuit regeneration.
View Article and Find Full Text PDFNeural Regen Res
September 2025
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Spinal V3 interneurons are glutamatergic neurons that are distributed among the dorsal, intermediate, and ventral spinal cord. They are involved in broad neural circuit connections in the central nervous system. Functionally, they play important roles in locomotion, such as the maintenance of robust and balanced gaits during walking.
View Article and Find Full Text PDFRes Sq
August 2025
UC San Francisco.
Paradoxical kinesia-the temporary alleviation of motor deficits by powerful, urgent stimuli in Parkinson's disease (PD)-remains poorly understood at the neural circuit level. Through chemo-genetic ablation of tyrosine hydroxylase-expressing neurons in larval zebrafish and brain-wide calcium imaging under head-fixed, tail-free conditions, we uncovered a neural mechanism underlying this phenomenon. While catecholamine (CA)-deficient larvae exhibited severe locomotor deficits during free swimming, they showed paradoxical recovery of tail movements during whole-brain neural activity imaging.
View Article and Find Full Text PDFBehav Neurosci
September 2025
University of Vermont, Department of Psychological Science.
Pituitary adenylate cyclase-activating polypeptide (PACAP, ) is a highly conserved neuropeptide that plays essential roles in numerous physiological functions, and central PACAP signaling has been associated with mechanisms regulating stress-induced psychopathologies. PACAP binds to several receptor subtypes, including PAC1 (), VPAC1 (), and VPAC2 (), to activate several signaling cascades that can alter neuronal excitability and enhance indices of neuroplasticity, and much of our prior work has suggested that the anxiogenic effects of bed nucleus of the stria terminalis (BNST) PACAP depend on the activation of PAC1 receptors. To complement our previous work that evaluated the roles of BNST PACAP expression and secretion in anxiety-related responses, we employed in the current work chemogenetic approaches in male PAC1-Ires-Cre mice to directly and specifically modulate the activities of BNST PAC1 receptor-expressing neurons.
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