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Trends in Genetics : TIG Jan 2024Proprioception - the sense of body position in space - is intimately linked to motor control. Here, we briefly review the current knowledge of the proprioceptive system...
Proprioception - the sense of body position in space - is intimately linked to motor control. Here, we briefly review the current knowledge of the proprioceptive system and how advances in the genetic characterisation of proprioceptive sensory neurons in mice promise to dissect its role in health and disease.
Topics: Mice; Animals; Proprioception; Sensory Receptor Cells
PubMed: 37926636
DOI: 10.1016/j.tig.2023.10.006 -
World Journal of Clinical Cases Mar 2021Clinical studies have found that patients withcervical degenerative disease are usually accompanied by dizziness. Anterior cervical surgery can eliminate not only... (Review)
Review
Clinical studies have found that patients withcervical degenerative disease are usually accompanied by dizziness. Anterior cervical surgery can eliminate not only chronic neck pain, cervical radiculopathy or myelopathy, but also dizziness. Immunohistochemical studies show that a large number of mechanoreceptors, especially Ruffini corpuscles, are present in degenerated cervical discs. The available evidence suggests a key role of Ruffini corpuscles in the pathogenesis of dizziness caused by cervical degenerative disease (. cervical discogenic dizziness). Disc degeneration is characterized by an elevation of inflammatory cytokines, which stimulates the mechanoreceptors in degenerated discs and results in peripheral sensitization. Abnormal cervical proprioceptive inputs from the mechanoreceptors are transmitted to the central nervous system, resulting in sensory mismatches with vestibular and visual information and leads to dizziness. In addition, neck pain caused by cervical disc degeneration can play a key role in cervical discogenic dizziness by increasing the sensitivity of muscle spindles. Like cervical discogenic pain, the diagnosis of cervical discogenic dizziness can be challenging and can be made only after other potential causes of dizziness have been ruled out. Conservative treatment is effective for the majority of patients. Existing basic and clinical studies have shown that cervical intervertebral disc degeneration can lead to dizziness.
PubMed: 33850933
DOI: 10.12998/wjcc.v9.i9.2146 -
Experimental Physiology Jan 2024Our objective was to evaluate an ex vivo muscle-nerve preparation used to study mechanosensory signalling by low threshold mechanosensory receptors (LTMRs).... (Review)
Review
Our objective was to evaluate an ex vivo muscle-nerve preparation used to study mechanosensory signalling by low threshold mechanosensory receptors (LTMRs). Specifically, we aimed to assess how well the ex vivo preparation represents in vivo firing behaviours of the three major LTMR subtypes of muscle primary sensory afferents, namely type Ia and II muscle spindle (MS) afferents and type Ib tendon organ afferents. Using published procedures for ex vivo study of LTMRs in mouse hindlimb muscles, we replicated earlier reports on afferent firing in response to conventional stretch paradigms applied to non-contracting, that is passive, muscle. Relative to in vivo studies, stretch-evoked firing for confirmed MS afferents in the ex vivo preparation was markedly reduced in firing rate and deficient in encoding dynamic features of muscle stretch. These deficiencies precluded conventional means of discriminating type Ia and II afferents. Muscle afferents, including confirmed Ib afferents were often indistinguishable based on their similar firing responses to the same physiologically relevant stretch paradigms. These observations raise uncertainty about conclusions drawn from earlier ex vivo studies that either attribute findings to specific afferent types or suggest an absence of treatment effects on dynamic firing. However, we found that replacing the recording solution with bicarbonate buffer resulted in afferent firing rates and profiles more like those seen in vivo. Improving representation of the distinctive sensory encoding properties in ex vivo muscle-nerve preparations will promote accuracy in assigning molecular markers and mechanisms to heterogeneous types of muscle mechanosensory neurons.
Topics: Mice; Animals; Muscle Spindles; Tendons; Signal Transduction; Neurons; Neurons, Afferent
PubMed: 37119460
DOI: 10.1113/EP090763 -
Journal of Oral Science 2017Neurons in the trigeminal mesencephalic nucleus (Vmes) receive deep sensation (proprioception) from jaw-closing muscle spindles and periodontal ligaments and project... (Review)
Review
Neurons in the trigeminal mesencephalic nucleus (Vmes) receive deep sensation (proprioception) from jaw-closing muscle spindles and periodontal ligaments and project primarily to the jaw-closing motoneuron pool (jaw-closing nucleus) of the trigeminal motor nucleus and to the supratrigeminal nucleus. Numerous articles have described the morphology and physiology of the central projections of Vmes afferents originating from the muscle spindles and periodontal ligaments. However, no report has provided a detailed description of projection and synaptic connectivity, especially of single afferents, and their functional implications. In this review, we reanalyze data obtained by single intra-axonal recording and labeling of functionally identified Vmes muscle spindle afferents and periodontal ligament afferents and by electron microscopic observation of their projection features and synaptic organization of boutons, to compare the data for the jaw-closing nucleus and supratrigeminal nucleus. Our analysis shows that each Vmes afferent type has characteristic projection pattern and synaptic feature that may be important in jaw-reflex control.
Topics: Animals; Jaw; Mesencephalon; Neurons; Reflex; Synapses; Trigeminal Nerve
PubMed: 28637975
DOI: 10.2334/josnusd.16-0845 -
Developmental Dynamics : An Official... Apr 2018Motor behaviors are precisely controlled by the integration of sensory and motor systems in the central nervous system (CNS). Proprioceptive sensory neurons, key... (Review)
Review
Motor behaviors are precisely controlled by the integration of sensory and motor systems in the central nervous system (CNS). Proprioceptive sensory neurons, key components of the sensory system, are located in the dorsal root ganglia and project axons both centrally to the spinal cord and peripherally to muscles and tendons, communicating peripheral information about the body to the CNS. Changes in muscle length detected by muscle spindles, and tension variations in tendons conveyed by Golgi tendon organs, are communicated to the CNS through group Ia /II, and Ib proprioceptive sensory afferents, respectively. Group Ib proprioceptive sensory neurons connect with motor neurons indirectly through spinal interneurons, whereas group Ia/II axons form both direct (monosynaptic) and indirect connections with motor neurons. Although monosynaptic sensory-motor circuits between spindle proprioceptive sensory neurons and motor neurons have been extensively studied since 1950s, the molecular mechanisms underlying their formation and upkeep have only recently begun to be understood. We will discuss our current understanding of the molecular foundation of monosynaptic circuit development and maintenance involving proprioceptive sensory neurons and motor neurons in the mammalian spinal cord. Developmental Dynamics 247:581-587, 2018. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Central Nervous System; Humans; Motor Neurons; Proprioception; Sensory Receptor Cells; Spinal Cord
PubMed: 29226492
DOI: 10.1002/dvdy.24611 -
Journal of Anatomy Aug 2015Mechanotransduction by proprioceptive sensory organs is poorly understood. Evidence was recently shown that muscle spindle and hair follicle primary afferents... (Review)
Review
Mechanotransduction by proprioceptive sensory organs is poorly understood. Evidence was recently shown that muscle spindle and hair follicle primary afferents (lanceolates) constantly release glutamate from synaptic-like vesicles (SLVs) within the terminals. The secreted glutamate activates a highly unusual metabotropic glutamate receptor (mGluR) to modulate the firing rate (spindles) and SLV recycling (lanceolates). This receptor has yet to be isolated and sequenced. To further investigate this receptor's pharmacology, ligands selective for classical mGluRs have been recently characterised for their ability to alter stretch-evoked spindle firing and SLV endocytosis in these different endings. Here, it is described how the results of these screens facilitated the development of novel compounds to be used in the process of isolating and sequencing of this non-canonical mGluR. This study shows how the compounds were tested for their ability to alter stretch-evoked afferent firing in muscle spindles and SLV endocytosis in the lanceolate endings of hair follicles to ensure they maintained their ability to bind to the receptor. For the development of novel compounds, kainate was chosen as the parent ligand due to its potency and ease of chemical modification. Novel kainate derivatives were then synthesised and tested to find potent analogues suitable for 'click-chemistry', an established technique for relatively quick, cheap, stereospecific and high-yield chemical modifications (Angewandte Chemie (International ed. in English), 40, 2001, pp2004). Of the novel kainate analogues developed, unfortunately ZCZ49 and ZCZ50 lost the ability to produce a significant change in spindle stretch-evoked firing. However, ZCZ90 was as potent as kainate, increasing firing by a similar margin at 1 μm (n = 8; P < 0.001). The addition of either a biotin or a fluorescein side group to ZCZ90, using the click-chemistry technique, did not affect the potency and hence these compounds will be used in further studies of the receptor. As well as the development of these compounds, the study found not only many similarities, but also some key differences between the two types of primary mechanosensory endings investigated. These differences must be taken into account in further study. However, they also present an intriguing opportunity for these receptors to be targeted selectively to modulate ending sensitivity as treatments for muscle spasm in multiple sclerosis and spinal cord injury, and possibly even baroreceptor firing to treat hypertension.
Topics: Animals; Endocytosis; Hair Follicle; Mammals; Mechanotransduction, Cellular; Molecular Sequence Data; Muscle Spindles; Neurons, Afferent; Proprioception; Pyridinium Compounds; Quaternary Ammonium Compounds; Receptors, Metabotropic Glutamate; Synaptic Vesicles
PubMed: 26053109
DOI: 10.1111/joa.12319 -
Journal of Neurochemistry Jan 2016Inhibition of BACE1 is being pursued as a therapeutic target to treat patients suffering from Alzheimer's disease because BACE1 is the sole β-secretase that generates... (Review)
Review
Inhibition of BACE1 is being pursued as a therapeutic target to treat patients suffering from Alzheimer's disease because BACE1 is the sole β-secretase that generates β-amyloid peptide. Knowledge regarding other cellular functions of BACE1 is therefore critical for the safe use of BACE1 inhibitors in human patients. Neuregulin-1 (Nrg1) is a BACE1 substrate and BACE1 cleavage of Nrg1 is critical for signaling functions in myelination, remyelination, synaptic plasticity, normal psychiatric behaviors, and maintenance of muscle spindles. This review summarizes the most recent discoveries associated with BACE1-dependent Nrg1 signaling in these areas. This body of knowledge will help to provide guidance for preventing unwanted Nrg1-based side effects following BACE1 inhibition in humans. To initiate its signaling cascade, membrane anchored Neuregulin (Nrg), mainly type I and III β1 Nrg1 isoforms and Nrg3, requires ectodomain shedding. BACE1 is one of such indispensable sheddases to release the functional Nrg signaling fragment. The dependence of Nrg on the cleavage by BACE1 is best manifested by disrupting the critical role of Nrg in the control of axonal myelination, schizophrenic behaviors as well as the formation and maintenance of muscle spindles.
Topics: Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Humans; Models, Molecular; Nervous System Diseases; Neuregulin-1; Signal Transduction
PubMed: 26465092
DOI: 10.1111/jnc.13395 -
Cells, Tissues, Organs 2019We examined the six small lateral rotators of the hip joint, which is one of the most flexible joints and allows kinematically complex motions of the hindlimb, to...
We examined the six small lateral rotators of the hip joint, which is one of the most flexible joints and allows kinematically complex motions of the hindlimb, to elucidate the functional differentiation among these muscles and to test the hypothesis that species-specific characteristics in hindlimb use during locomotion are reflected in the muscle spindle density and in other parameters of the deep small hip joint rotators. For these purposes, we estimated the number of muscle spindles of the superior gemellus muscle (SG), inferior gemellus muscle, quadratus femoris muscle, obturator internus muscle (OI), obturator externus muscle, and piriformis muscle in three Japanese macaques and a gibbon, using 30-µm-thick serial sections throughout each muscle length after azan staining. The numbers of muscle spindles per 10,000 muscle fibers were determined to compare inter-muscle variation. The spindle density was highest in the SG and lowest in the OI in the Japanese macaques, suggesting that the SG, which is attached to the tendon of the OI, functions as a kinesiological monitor of the OI. On the other hand, SG the was missing in the gibbon, and the OI in the gibbon contained more spindles than that in the Japanese macaques. This suggests that the SG and the OI fused into one muscle in the gibbon. We postulate that the relative importance of the deep small hip rotator muscles differs between the Japanese macaques and gibbon and that the gibbon's muscles are less differentiated in terms of the spindle density, probably because this brachiating species uses its hindlimbs less frequently.
Topics: Animals; Haplorhini; Hindlimb; Hylobates; Macaca; Macaca fuscata; Muscle Fibers, Skeletal; Muscle Spindles; Primates; Thigh
PubMed: 31927538
DOI: 10.1159/000504958 -
Anatomical Record (Hoboken, N.J. : 2007) Mar 2024The objective of this study was to analyze the proprioceptive innervation of human lips, especially of the orbicularis oris muscle, since it is classically accepted that...
The objective of this study was to analyze the proprioceptive innervation of human lips, especially of the orbicularis oris muscle, since it is classically accepted that facial muscles lack typical proprioceptors, that is, muscle spindles, but recently this has been doubted. Upper and lower human lips (n = 5) from non-embalmed frozen cadavers were immunostained for detection of S100 protein (to identify nerves and sensory nerve formations), myosin heavy chain (to label muscle fibers within muscle spindles), and the mechano-gated ion channel PIEZO2. No muscle spindles were found, but there was a high density of sensory nerve formations, which were morphologically heterogeneous, and in some cases resemble Ruffini-like and Pacinian sensory corpuscles. The axons of these sensory formations displayed immunoreactivity for PIEZO2. Human lip muscles lack typical proprioceptors but possess a dense sensory innervation which can serve the lip proprioception.
Topics: Humans; Lip; Proprioception; Sensory Receptor Cells; Facial Muscles; Pacinian Corpuscles
PubMed: 37712912
DOI: 10.1002/ar.25324 -
Journal of Anatomy Aug 2015This article summarises progress to date over an exciting and very enjoyable first 15 years of collaboration with Bob Banks. Our collaboration began when I contacted him... (Review)
Review
This article summarises progress to date over an exciting and very enjoyable first 15 years of collaboration with Bob Banks. Our collaboration began when I contacted him with (to me) an unexpected observation that a dye used to mark recycling synaptic vesicle membrane at efferent terminals also labelled muscle spindle afferent terminals. This observation led to the re-discovery of a system of small clear vesicles present in all vertebrate primary mechanosensory nerve terminals. These synaptic-like vesicles (SLVs) have been, and continue to be, the major focus of our work. This article describes our characterisation of the properties and functional significance of these SLVs, combining our complementary skills: Bob's technical expertise and encyclopaedic knowledge of mechanosensation with my experience of synaptic vesicles and the development of the styryl pyridinium dyes, of which the most widely used is FM1-43. On the way we have found that SLVs seem to be part of a constitutive glutamate secretory system necessary to maintain the stretch-sensitivity of spindle endings. The glutamate activates a highly unusual glutamate receptor linked to phospholipase D activation, which we have termed the PLD-mGluR. It has a totally distinct pharmacology first described in the hippocampus nearly 20 years ago but, like the SLVs that were first described over 50 years ago, has since been little researched. Yet, our evidence and literature searches suggest this glutamate/SLV/PLD-mGluR system is a ubiquitous feature of mechanosensory endings and, at least for spindles, is essential for maintaining mechanosensory function. This article summarises how this system integrates with the classical model of mechanosensitive channels in spindles and other mechanosensory nerve terminals, including hair follicle afferents and baroreceptors controlling blood pressure. Finally, in this time when there is an imperative to show translational relevance, I describe how this fascinating system might actually be a useful therapeutic drug target for clinical conditions such as hypertension and muscle spasticity. This has been a fascinating 15-year journey in collaboration with Bob who, as well as having an astute scientific mind, is also a great enthusiast, motivator and friend. I hope this exciting and enjoyable journey will continue well into the future.
Topics: Fluorescent Dyes; Glutamic Acid; Mechanotransduction, Cellular; Muscle Spindles; Nerve Endings; Neurons, Efferent; Pyridinium Compounds; Quaternary Ammonium Compounds; Receptors, Glutamate; Signal Transduction; Synaptic Vesicles
PubMed: 26179025
DOI: 10.1111/joa.12337