Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Fiber types in mammalian skeletal muscles.

We describe the formation, maturation, elimination, maintenance, and regeneration of vertebrate neuromuscular junctions (NMJs), the best studied of all synapses. The NMJ forms in a series of steps that involve the exchange of signals among its three cellular components--nerve terminal, muscle fiber, and Schwann cell. Although essentially any motor axon can form NMJs with any muscle fiber, an additional set of cues biases synapse formation in favor of appropriate partners. The NMJ is functional at birth but undergoes numerous alterations postnatally. One step in maturation is the elimination of excess inputs, a competitive process in which the muscle is an intermediary. Once elimination is complete, the NMJ is maintained stably in a dynamic equilibrium that can be perturbed to initiate remodeling. NMJs regenerate following damage to nerve or muscle, but this process differs in fundamental ways from embryonic synaptogenesis. Finally, we consider the extent to which the NMJ is a suitable model for development of neuron-neuron synapses.

Development of the vertebrate neuromuscular junction.

The Neurology of Eye Movements, Edition 5, by R. John Leigh, M.D. and David S. Zee MD Foreword Chapter 1: A Survey of Eye Movements: Characteristics and Teleology Chapter 2: The Ocular Motor Periphery Chapter 3: The Vestibular-Optokinetic System Chapter 4: The Saccadic System Chapter 5: Smooth Visual Tracking and Fixation Chapter 6: Gaze Holding and The Neural Integrator Chapter 7: The Neural Basis for Conjugate Eye Movements Chapter 8: Eye-Head Movements Chapter 9: Vergence Eye Movements Chapter 10: Diagnosis of Peripheral Ocular Motor Palsies And Strabismus Chapter 11: Diagnosis of Nystagmus and Saccadic Intrusions Chapter 12: Diagnosis and Management of Vestibular Disorders Chapter 13: Disorders of Ocular Motility Due To Disease of the Brainstem, Cerebellum and Diencephalon Chapter 14: Disorders of Ocular Motility With Disease Affecting The Basal Ganglia, Cerebral Cortex, And In Systemic Conditions Appendix A: A Summary Scheme for the Bedside Ocular Motor Examination Appendix B: A Summary of Methods for Measuring Eye Movements Appendix C: Tables of Ocular Motor Findings in Hereditary Ataxias Appendix D: Table of Videos and their Legends

The neurology of eye movements

The evolution of free radicals and oxidative stress

The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where DED is a comorbidity. Prior to diagnosis, it is important to exclude conditions that can mimic DED with the aid of triaging questions. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the conduct of diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin). Meibomian gland dysfunction, lipid thickness/dynamics and tear volume assessment and their severity allow sub-classification of DED (as predominantly evaporative or aqueous deficient) which informs the management of DED. Videos of these diagnostic and sub-classification techniques are available on the TFOS website. It is envisaged that the identification of the key tests to diagnose and monitor DED and its sub-classifications will inform future epidemiological studies and management clinical trials, improving comparability, and enabling identification of the sub-classification of DED in which different management strategies are most efficacious.

TFOS DEWS II Diagnostic Methodology report

Single-unit recordings were made from midbrain areas in monkeys trained to make both conjugate and disjunctive (vergence) eye movements. Previous work had identified cells with a firing rate proportional to the vergence angle, without regard to the direction of conjugate gaze. The present study describes the activity of neurons that burst for disjunctive eye movements. Convergence burst cells display a discrete burst of activity just before and during convergence eye movements. For most of these cells, the profile of the burst is correlated with instantaneous vergence velocity and the number of spikes in the burst is correlated with the size of the vergence movement. Some of these cells also have a tonic firing rate that is positively correlated with vergence angle (convergence burst-tonic cells). Divergence burst cells have similar properties, except that they fire for divergent and not convergent movements. Divergence burst cells are encountered far less often than convergence burst cells. Both convergence and divergence burst cells were found in an area of the mesencephalic reticular formation just dorsal and lateral to the oculomotor nucleus. Convergence burst cells were also recorded in another more dorsal mesencephalic region, rostral to the superior colliculus. Both of the areas also contain cells that encode vergence angle. Models of the vergence system derived from psychophysical data imply the existence of a vergence integrator, the output of which is vergence angle. Some models also suggest the presence of a parallel element that improves the frequency response of the vergence system, but has no effect on the steady-state behavior of the system. Vergence burst cells would be suitable inputs to a vergence integrator. By providing a vergence velocity signal to motoneurons, they may improve the dynamic response of the vergence system. The behavior of vergence burst cells during vergence movements is similar to that of the medium-lead burst cells during saccades. The proposed roles for vergence velocity cells are analogous to those of the saccadic burst cells. In this respect, the neural organization of the vergence system resembles that of the saccadic system, despite the distinct difference in the kinematics of these two types of eye movements.

Neural control of vergence eye movements: neurons encoding vergence velocity

Extraocular muscles: basic and clinical aspects of structure and function.

Cerebellotectal pathways in the macaque: implications for collicular generation of saccades.

Congenital fibrosis of the extraocular muscles is an autosomal dominant congenital disorder characterized by bilateral ptosis, restrictive external ophthalmoplegia with the eyes partially or completely fixed in an infraducted (downward) and strabismic position, and markedly limited and aberrant residual eye movements. It has been generally thought that these clinical abnormalities result from myopathic fibrosis of the extraocular muscles. We describe the intracranial and orbital pathology of 1 and the muscle pathology of 2 other affected members of a family with chromosome 12-linked congenital fibrosis of the extraocular muscles. There is an absence of the superior division of the oculomotor nerve and its corresponding alpha motor neurons, and abnormalities of the levator palpebrae superioris and rectus superior (the muscles innervated by the superior division of the oculomotor nerve). In addition, increased numbers of internal nuclei and central mitochondrial clumping are found in other extraocular muscles, suggesting that the muscle pathology extends beyond the muscles innervated by the superior division of cranial nerve III. This report presents evidence that congenital fibrosis of the extraocular muscles results from an abnormality in the development of the extraocular muscle lower motor neuron system.

https://www.childrenshospital.org/~/media/Research%20and%20Innovation/Research%20Labs/Beggs%20Lab/PDFs/63.ashx

Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles.

The levator palpebrae superioris and orbicularis oculi are antagonistic muscles that function during movements of the eyelid. The levator also functions in conjunction with superior and inferior rectus muscles in coordinated eye/lid movements. The present study examined the innervation and morphology of these muscles in Cynomolgous monkeys (Macaca fascicularis) in order to provide a better understanding of the anatomical substrate for lid movements. Motoneurons innervating the levator and orbicularis muscles were identified and localized by retrograde transport of WGA/HRP and HRP. Retrogradely labelled levator motoneurons were distributed bilaterally throughout the caudal central division of the oculomotor nucleus. A few labelled cells were also present within the contralateral superior rectus division, possibly because of the spread of tracer at the injection site. The possibility that individual motoneurons collateralize to innervate the levator muscle bilaterally was tested by using double retrograde labelling techniques. Doubly labelled levator motoneurons could not be detected by using a combination of tracers (HRP and Fast Blue). Motoneurons innervating the upper lid portion of the orbicularis oculi muscle were distributed within the dorsal subdivision of the ipsilateral facial motor nucleus, with a few neurons in the corresponding locus of the contralateral facial nucleus. Species differences in levator motoneuron distribution, particularly distinctions in lateral-eyed versus frontal-eyed mammals, are discussed in relation to the neural control of lid movements. The levator palpebrae superioris contains three of the same ultrastructurally defined types of singly innervated muscle fiber found in the global layer of other extraocular muscles and an additional, unique slow-twitch fiber type. Moreover, the multiply innervated fiber types so characteristic of the other extraocular muscles are conspicuously absent from levator muscles. Unlike the rectus and oblique extraocular muscles, the levator lacks a layered distribution of fiber types. The morphological profiles of levator muscle fiber types are such that they generally do not respect traditional fiber classification schemes, but are consistent with a role for the levator in sustained elevation of the lid. The orbicularis oculi muscle, by contrast, exhibited three distinct fiber types that resembled categories of skeletal muscle twitch fibers. One slow-twitch and two fast-twitch fiber types were noted. On the basis of oxidative enzyme profiles and mitochondrial content, the majority of orbicularis oculi fibers would be fatigue-prone, an assessment consistent with their rapid onset/offset of acti

John D. Porter

Papers

Neural control of vergence eye movements: neurons encoding vergence velocity

Extraocular muscles: basic and clinical aspects of structure and function.

Cerebellotectal pathways in the macaque: implications for collicular generation of saccades.

Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles.

Morphological substrate for eyelid movements: Innervation and structure of primate levator palpebrae superioris and orbicularis oculi muscles