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Cell Jan 2023The cortex influences movement by widespread top-down projections to many nervous system regions. Skilled forelimb movements require brainstem circuitry in the medulla;...
The cortex influences movement by widespread top-down projections to many nervous system regions. Skilled forelimb movements require brainstem circuitry in the medulla; however, the logic of cortical interactions with these neurons remains unexplored. Here, we reveal a fine-grained anatomical and functional map between anterior cortex (AC) and medulla in mice. Distinct cortical regions generate three-dimensional synaptic columns tiling the lateral medulla, topographically matching the dorso-ventral positions of postsynaptic neurons tuned to distinct forelimb action phases. Although medial AC (MAC) terminates ventrally and connects to forelimb-reaching-tuned neurons and its silencing impairs reaching, lateral AC (LAC) influences dorsally positioned neurons tuned to food handling, and its silencing impairs handling. Cortico-medullary neurons also extend collaterals to other subcortical structures through a segregated channel interaction logic. Our findings reveal a precise alignment between cortical location, its function, and specific forelimb-action-tuned medulla neurons, thereby clarifying interaction principles between these two key structures and beyond.
Topics: Mice; Animals; Movement; Neurons; Forelimb; Brain Stem
PubMed: 36608651
DOI: 10.1016/j.cell.2022.12.009 -
Nature Reviews. Neuroscience Jan 2006Oligodendrocyte precursors first arise in a restricted ventral part of the embryonic spinal cord and migrate laterally and dorsally from there. Later, secondary sources... (Review)
Review
Oligodendrocyte precursors first arise in a restricted ventral part of the embryonic spinal cord and migrate laterally and dorsally from there. Later, secondary sources develop in the dorsal cord. Normally, the ventrally-derived precursors compete with and suppress their dorsal counterparts. There are also ventral and dorsal sources in the forebrain, but here the more dorsal precursors prevail and the ventral-most lineage is eliminated during postnatal life. How do the different populations compete and what is the outcome of the competition? Do different embryonic origins signify different functional subgroups of oligodendrocyte?
Topics: Animals; Cell Differentiation; Central Nervous System; Embryonic Development; Oligodendroglia; Stem Cells
PubMed: 16371946
DOI: 10.1038/nrn1826 -
Current Biology : CB Nov 2023The elephant trunk operates as a muscular hydrostat and is actuated by the most complex musculature known in animals. Because the number of trunk muscles is unclear, we...
The elephant trunk operates as a muscular hydrostat and is actuated by the most complex musculature known in animals. Because the number of trunk muscles is unclear, we performed dense reconstructions of trunk muscle fascicles, elementary muscle units, from microCT scans of an Asian baby elephant trunk. Muscle architecture changes markedly across the trunk. Trunk tip and finger consist of about 8,000 extraordinarily filigree fascicles. The dexterous finger consists exclusively of microscopic radial fascicles pointing to a role of muscle miniaturization in elephant dexterity. Radial fascicles also predominate (at 82% volume) the remainder of the trunk tip, and we wonder if radial muscle fascicles are of particular significance for fine motor control of the dexterous trunk tip. By volume, trunk-shaft muscles comprise one-third of the numerous, small radial muscle fascicles; two-thirds of the three subtypes of large longitudinal fascicles (dorsal longitudinals, ventral outer obliques, and ventral inner obliques); and a small fraction of transversal fascicles. Shaft musculature is laterally, but not radially, symmetric. A predominance of dorsal over ventral radial muscles and of ventral over dorsal longitudinal muscles may result in a larger ability of the shaft to extend dorsally than ventrally and to bend inward rather than outward. There are around 90,000 trunk muscle fascicles. While primate hand control is based on fine control of contraction by the convergence of many motor neurons on a small set of relatively large muscles, evolution of elephant grasping has led to thousands of microscopic fascicles, which probably outnumber facial motor neurons.
Topics: Animals; Elephants; Muscle, Skeletal; Motor Neurons
PubMed: 37757829
DOI: 10.1016/j.cub.2023.09.007 -
Frontiers in Immunology 2023Encephalitis is a devastating neurologic disorder with high morbidity and mortality. Autoimmune causes are roughly as common as infectious ones. N-methyl-D-aspartic acid...
BACKGROUND AND OBJECTIVES
Encephalitis is a devastating neurologic disorder with high morbidity and mortality. Autoimmune causes are roughly as common as infectious ones. N-methyl-D-aspartic acid receptor (NMDAR) encephalitis (NMDARE), characterized by serum and/or spinal fluid NMDAR antibodies, is the most common form of autoimmune encephalitis (AE). A translational rodent NMDARE model would allow for pathophysiologic studies of AE, leading to advances in the diagnosis and treatment of this debilitating neuropsychiatric disorder. The main objective of this work was to identify optimal active immunization conditions for NMDARE in mice.
METHODS
Female C57BL/6J mice aged 8 weeks old were injected subcutaneously with an emulsion of complete Freund's adjuvant, killed and dessicated , and a 30 amino acid peptide flanking the NMDAR GluN1 subunit N368/G369 residue targeted by NMDARE patients' antibodies. Three different induction methods were examined using subcutaneous injection of the peptide emulsion mixture into mice in 1) the ventral surface, 2) the dorsal surface, or 3) the dorsal surface with reimmunization at 4 and 8 weeks (boosted). Mice were bled biweekly and sacrificed at 2, 4, 6, 8, and 14 weeks. Serum and CSF NMDAR antibody titer, mouse behavior, hippocampal cell surface and postsynaptic NMDAR cluster density, and brain immune cell entry and cytokine content were examined.
RESULTS
All immunized mice produced serum and CSF NMDAR antibodies, which peaked at 6 weeks in the serum and at 6 (ventral and dorsal boosted) or 8 weeks (dorsal unboosted) post-immunization in the CSF, and demonstrated decreased hippocampal NMDAR cluster density by 6 weeks post-immunization. In contrast to dorsally-immunized mice, ventrally-induced mice displayed a translationally-relevant phenotype including memory deficits and depressive behavior, changes in cerebral cytokines, and entry of T-cells into the brain at the 4-week timepoint. A similar phenotype of memory dysfunction and anxiety was seen in dorsally-immunized mice only when they were serially boosted, which also resulted in higher antibody titers.
DISCUSSION
Our study revealed induction method-dependent differences in active immunization mouse models of NMDARE disease. A novel ventrally-induced NMDARE model demonstrated characteristics of AE earlier compared to dorsally-induced animals and is likely suitable for most short-term studies. However, boosting and improving the durability of the immune response might be preferred in prolonged longitudinal studies.
Topics: Mice; Female; Animals; Emulsions; Mice, Inbred C57BL; Encephalitis; Antibodies; Receptors, N-Methyl-D-Aspartate; Vaccination; Disease Models, Animal; Autoimmune Diseases of the Nervous System
PubMed: 37520559
DOI: 10.3389/fimmu.2023.1177672 -
Surgical Neurology International 2021The epidural ligaments (ELs) (of Hofmann) were described as fibrous bands interconnecting the ventrolateral spinal dura and the posterior longitudinal ligament below L1.... (Review)
Review
BACKGROUND
The epidural ligaments (ELs) (of Hofmann) were described as fibrous bands interconnecting the ventrolateral spinal dura and the posterior longitudinal ligament below L1. They are hardly ever discussed in the literature or considered in hypothesis-driven basic science experiments or spine biomechanical models.
METHODS
Intraoperative photographs were obtained to illustrate a group of posterolateral spinal ELs. In addition, electronic database searches (PubMed, Ovid Embase, and SCOPUS) were utilized to summarize the anatomy, and relevant clinical and surgical factors impacting these ELs.
RESULTS
ELs attach circumferentially at most spinal levels. They anchor the nerve root sleeves ventrally, and therefore, may play a role in the some idiopathic neurologic deficits (e.g., postoperative radiculopathies, C5 palsies) in patients without radiological compression. The posterolateral ELs originate on the dura dorsal to the nerve root sleeves and insert on the ipsilateral lamina, interlaminar ligament, and facet capsule. They appear to be continuous with the peridural membrane, a fibrovascular sheath that surrounds the thecal sac and serves as a scaffold for the internal vertebral venous plexus of Batson and epidural fat.
CONCLUSION
The spinal ELs should be divided sharply during surgery to prevent durotomies, especially in patients with advanced spondylosis and facet arthropathy. Disconnecting these ligaments releases the thecal sac laterally and ventrally, allowing for medial mobilization when performing discectomies or for working in the ventral epidural space.
PubMed: 33598349
DOI: 10.25259/SNI_894_2020 -
TheScientificWorldJournal Jun 2010Knowledge of penile embryology and anatomy is essential to any pediatric urologist in order to fully understand and treat congenital anomalies. Sex differentiation of... (Review)
Review
Knowledge of penile embryology and anatomy is essential to any pediatric urologist in order to fully understand and treat congenital anomalies. Sex differentiation of the external genitalia occurs between the 7th and 17th weeks of gestation. The Y chromosome initiates male differentiation through the SRY gene, which triggers testicular development. Under the influence of androgens produced by the testes, external genitalia then develop into the penis and scrotum. Dorsal nerves supply penile skin sensation and lie within Buck's fascia. These nerves are notably absent at the 12 o'clock position. Perineal nerves supply skin sensation to the ventral shaft skin and frenulum. Cavernosal nerves lie within the corpora cavernosa and are responsible for sexual function. Paired cavernosal, dorsal, and bulbourethral arteries have extensive anastomotic connections. During erection, the cavernosal artery causes engorgement of the cavernosa, while the deep dorsal artery leads to glans enlargement. The majority of venous drainage occurs through a single, deep dorsal vein into which multiple emissary veins from the corpora and circumflex veins from the spongiosum drain. The corpora cavernosa and spongiosum are all made of spongy erectile tissue. Buck's fascia circumferentially envelops all three structures, splitting into two leaves ventrally at the spongiosum. The male urethra is composed of six parts: bladder neck, prostatic, membranous, bulbous, penile, and fossa navicularis. The urethra receives its blood supply from both proximal and distal directions.
Topics: Humans; Male; Penis
PubMed: 20602076
DOI: 10.1100/tsw.2010.112 -
Journal of Neuroendocrinology May 2019The adult hypothalamus is subdivided into distinct domains: pre-optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to... (Review)
Review
The adult hypothalamus is subdivided into distinct domains: pre-optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to regulate homeostasis. The embryonic origins and the development of hypothalamic neurones, however, remain enigmatic. Here, we summarise recent studies in model organisms that challenge current views of hypothalamic development, which traditionally have attempted to map adult domains to correspondingly located embryonic domains. Instead, new studies indicate that hypothalamic neurones arise from progenitor cells that undergo anisotropic growth, expanding to a greater extent than other progenitors, and grow in different dimensions. We describe in particular how a multipotent Shh Fgf10-expressing progenitor population gives rise to progenitors throughout the basal hypothalamus that grow anisotropically and sequentially: first, a subset displaced rostrally give rise to anterior-ventral/tuberal neuronal progenitors; then a subset displaced caudally give rise to mammillary neuronal progenitors; and, finally, a subset(s) displaced ventrally give rise to tuberal infundibular glial progenitors. As this occurs, stable populations of Shh and Fgf10 progenitors form. We describe current understanding of the mechanisms that induce Shh /Fgf10 progenitors and begin to direct their differentiation to anterior-ventral/tuberal neuronal progenitors, mammillary neuronal progenitors and tuberal infundibular progenitors. Taken together, these studies suggest a new model for hypothalamic development that we term the "anisotropic growth model". We discuss the implications of the model for understanding the origins of adult hypothalamic neurones.
Topics: Animals; Fibroblast Growth Factor 10; Hedgehog Proteins; Humans; Hypothalamus; Models, Neurological; Neural Stem Cells; Neurons
PubMed: 31050853
DOI: 10.1111/jne.12727 -
The Journal of Neuroscience : the... Feb 2021Mossy cells (MCs) of the dentate gyrus (DG) are a major group of excitatory hilar neurons that are important for regulating activity of dentate granule cells. MCs are...
Mossy cells (MCs) of the dentate gyrus (DG) are a major group of excitatory hilar neurons that are important for regulating activity of dentate granule cells. MCs are particularly intriguing because of their extensive longitudinal connections within the DG. It has generally been assumed that MCs in the dorsal and ventral DG have similar patterns of termination in the inner one-third of the dentate molecular layer. Here, we demonstrate that axonal projections of MCs in these two regions are considerably different. MCs in dorsal and ventral regions were labeled selectively with Cre-dependent eYFP or mCherry, using two transgenic mouse lines (including both sexes) that express Cre-recombinase in MCs. At four to six weeks following unilateral labeling of MCs in the ventral DG, a dense band of fibers was present in the inner one-fourth of the molecular layer and extended bilaterally throughout the rostral-caudal extent of the DG, replicating the expected distribution of MC axons. In contrast, following labeling of MCs in the dorsal DG, the projections were more diffusely distributed. At the level of transfection, fibers were present in the inner molecular layer, but they progressively expanded into the middle molecular layer and, most ventrally, formed a distinct band in this region. Optical stimulation of these caudal fibers expressing ChR2 demonstrated robust EPSCs in ipsilateral granule cells and enhanced the effects of perforant path stimulation in the ventral DG. These findings suggest that MCs in the dorsal and ventral DG differ in the distribution of their axonal projections and possibly their function. Mossy cells (MCs), a major cell type in the hilus of the dentate gyrus (DG), are unique in providing extensive longitudinal and commissural projections throughout the DG. Although it has been assumed that all MCs have similar patterns of termination in the inner molecular layer of the DG, we discovered that the axonal projections of dorsal and ventral MCs differ. While ventral MC projections exhibit the classical pattern, with dense innervation in the inner molecular layer, dorsal MCs have a more diffuse distribution and expand into the middle molecular layer where they overlap and interact with innervation from the perforant path. These distinct locations and patterns of axonal projections suggest that dorsal and ventral MCs may have different functional roles.
Topics: Animals; Axons; Dentate Gyrus; Excitatory Postsynaptic Potentials; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mossy Fibers, Hippocampal; Optogenetics
PubMed: 33268544
DOI: 10.1523/JNEUROSCI.2455-20.2020