The Cortical Motor System in the Domestic Pig: Origin and Termination of the Corticospinal Tract and Cortico-Brainstem Projections

The anatomy of the cortical motor system and its relationship to motor repertoire in artiodactyls is for the most part unknown. We studied the origin and termination of the corticospinal tract (CST) and cortico-brainstem projections in domestic pigs. Pyramidal neurons were retrogradely labeled by injecting aminostilbamidine in the spinal segment C1. After identifying the dual origin of the porcine CST in the primary motor cortex (M1) and premotor cortex (PM), the axons descending from those regions to the spinal cord and brainstem were anterogradely labeled by unilateral injections of dextran alexa-594 in M1 and dextran alexa-488 in PM. Numerous corticospinal projections from M1 and PM were detected up to T6 spinal segment and showed a similar pattern of decussation and distribution in the white matter funiculi and the gray matter laminae. They terminated mostly on dendrites of the lateral intermediate laminae and the internal basilar nucleus, and some innervated the ventromedial laminae, but were essentially absent in lateral laminae IX. Corticofugal axons terminated predominantly ipsilaterally in the midbrain and bilaterally in the medulla oblongata. Most corticorubral projections arose from M1, whereas the mesencephalic reticular formation, superior colliculus, lateral reticular nucleus, gigantocellular reticular nucleus, and raphe received abundant axonal contacts from both M1 and PM. Our data suggest that the porcine cortical motor system has some common features with that of primates and humans and may control posture and movement through parallel motor descending pathways. However, less cortical regions project to the spinal cord in pigs, and the CST neither seems to reach the lumbar enlargement nor to have a significant direct innervation of cervical, foreleg motoneurons.

Location of Subcortical Microbleeds and Recovery of Consciousness After Severe Traumatic Brain Injury

Background:In patients with severe traumatic brain injury (TBI), coma is associated with impaired subcortical arousal mechanisms. However, it is unknown which nuclei involved in arousal (“arousal nuclei”) are implicated in coma pathogenesis and are compatible with coma recovery.Methods:We mapped an atlas of arousal nuclei in the brainstem, thalamus, hypothalamus, and basal forebrain onto 3 Tesla susceptibility-weighted images (SWI) in twelve patients with acute severe TBI who presented in coma and recovered consciousness within six months. We assessed the spatial distribution and volume of SWI microbleeds and evaluated the association of microbleed volume with the duration of unresponsiveness and functional recovery at six months.Results:There was no single arousal nucleus affected by microbleeds in all patients. Rather, multiple combinations of microbleeds in brainstem, thalamic, and hypothalamic arousal nuclei were associated with coma and were compatible with recovery of consciousness. Microbleeds were frequently detected in the midbrain (100%), thalamus (83%) and pons (75%). Within the brainstem, the microbleed incidence was largest within the mesopontine tegmentum (e.g., pedunculotegmental nucleus, mesencephalic reticular formation) and ventral midbrain (e.g., substantia nigra, ventral tegmental area). Brainstem arousal nuclei were partially affected by microbleeds, with microbleed volume not exceeding 35% of brainstem nucleus volume on average. Compared to microbleed volume within non-arousal brainstem regions, the microbleed volume within arousal brainstem nuclei accounted for a larger proportion of variance in the duration of unresponsiveness and 6-month Glasgow Outcome Scale-Extended scores.Conclusions:These results suggest resilience of arousal mechanisms in the human brain after severe TBI.

A Confocal Microscopic Study of Gene Transfer into the Mesencephalic Tegmentum of Juvenile Chum Salmon, Oncorhynchus keta, Using Mouse Adeno-Associated Viral Vectors

To date, data on the presence of adenoviral receptors in fish are very limited. In the present work, we used mouse recombinant adeno-associated viral vectors (rAAV) with a calcium indicator of the latest generation GCaMP6m that are usually applied for the dorsal hippocampus of mice but were not previously used for gene delivery into fish brain. The aim of our work was to study the feasibility of transduction of rAAV in the mouse hippocampus into brain cells of juvenile chum salmon and subsequent determination of the phenotype of rAAV-labeled cells by confocal laser scanning microscopy (CLSM). Delivery of the gene in vivo was carried out by intracranial injection of a GCaMP6m-GFP-containing vector directly into the mesencephalic tegmentum region of juvenile (one-year-old) chum salmon, Oncorhynchus keta. AAV incorporation into brain cells of the juvenile chum salmon was assessed at 1 week after a single injection of the vector. AAV expression in various areas of the thalamus, pretectum, posterior-tuberal region, postcommissural region, medial and lateral regions of the tegmentum, and mesencephalic reticular formation of juvenile O. keta was evaluated using CLSM followed by immunohistochemical analysis of the localization of the neuron-specific calcium binding protein HuCD in combination with nuclear staining with DAPI. The results of the analysis showed partial colocalization of cells expressing GCaMP6m-GFP with red fluorescent HuCD protein. Thus, cells of the thalamus, posterior tuberal region, mesencephalic tegmentum, cells of the accessory visual system, mesencephalic reticular formation, hypothalamus, and postcommissural region of the mesencephalon of juvenile chum salmon expressing GCaMP6m-GFP were attributed to the neuron-specific line of chum salmon brain cells, which indicates the ability of hippocampal mammal rAAV to integrate into neurons of the central nervous system of fish with subsequent expression of viral proteins, which obviously indicates the neuronal expression of a mammalian adenoviral receptor homolog by juvenile chum salmon neurons.

Cerebellar projections to the macaque midbrain tegmentum: Possible near response connections

Since most gaze shifts are to targets that lie at a different distance from the viewer than the current target, gaze changes commonly require a change in the angle between the eyes. As part of this response, lens curvature must also be adjusted with respect to target distance by the ciliary muscle. It has been suggested that projections by the cerebellar fastigial and posterior interposed nuclei to the supraoculomotor area (SOA), which lies immediately dorsal to the oculomotor nucleus and contains near response neurons, support this behavior. However, the SOA also contains motoneurons that supply multiply innervated muscle fibers (MIFs) and the dendrites of levator palpebrae superioris motoneurons. To better determine the targets of the fastigial nucleus in the SOA, we placed an anterograde tracer into this cerebellar nucleus in Macaca fascicularis monkeys and a retrograde tracer into their contralateral medial rectus, superior rectus, and levator palpebrae muscles. We only observed close associations between anterogradely labeled boutons and the dendrites of medial rectus MIF and levator palpebrae motoneurons. However, relatively few of these associations were present, suggesting these are not the main cerebellar targets. In contrast, labeled boutons in SOA, and in the adjacent central mesencephalic reticular formation (cMRF), densely innervated a subpopulation of neurons. Based on their location, these cells may represent premotor near response neurons that supply medial rectus and preganglionic Edinger–Westphal motoneurons. We also identified lens accommodation-related cerebellar afferent neurons via retrograde trans-synaptic transport of the N2c rabies virus from the ciliary muscle. They were found bilaterally in the fastigial and posterior interposed nuclei, in a distribution which mirrored that of neurons retrogradely labeled from the SOA and cMRF. Our results suggest these cerebellar neurons coordinate elements of the near response during symmetric vergence and disjunctive saccades by targeting cMRF and SOA premotor neurons.

Neural control of rapid binocular eye movements: Saccade-vergence burst neurons

During normal viewing, we direct our eyes between objects in three-dimensional (3D) space many times a minute. To accurately fixate these objects, which are usually located in different directions and at different distances, we must generate eye movements with appropriate versional and vergence components. These combined saccade-vergence eye movements result in disjunctive saccades with a vergence component that is much faster than that generated during smooth, symmetric vergence eye movements. The neural control of disjunctive saccades is still poorly understood. Recent anatomical studies suggested that the central mesencephalic reticular formation (cMRF), located lateral to the oculomotor nucleus, contains premotor neurons potentially involved in the neural control of these eye movements. We have therefore investigated the role of the cMRF in the control of disjunctive saccades in trained rhesus monkeys. Here, we describe a unique population of cMRF neurons that, during disjunctive saccades, display a burst of spikes that are highly correlated with vergence velocity. Importantly, these neurons show no increase in activity for either conjugate saccades or symmetric vergence. These neurons are termed saccade-vergence burst neurons (SVBNs) to maintain consistency with modeling studies that proposed that such a class of neuron exists to generate the enhanced vergence velocities observed during disjunctive saccades. Our results demonstrate the existence and characteristics of SVBNs whose activity is correlated solely with the vergence component of disjunctive saccades and, based on modeling studies, are critically involved in the generation of the disjunctive saccades required to view objects in our 3D world.

Case Studies in Neuroscience: Instability of the visual near triad in traumatic brain injury—evidence for a putative convergence integrator

Deficits of convergence and accommodation are common following traumatic brain injury, including mild traumatic brain injury, although the mechanism and localization of these deficits have been unclear and supranuclear control of the near-vision response has been incompletely understood. We describe a patient who developed profound instability of the near-vision response with inability to maintain convergence and accommodation following mild traumatic brain injury, who was identified to have a structural lesion on brain MRI in the pulvinar of the caudal thalamus, the pretectum, and the rostral superior colliculus. We discuss the potential relationship between posttraumatic clinical near-vision response deficits and the MRI lesion in this patient. We further propose that the MRI lesion location, specifically the rostral superior colliculus, participates in neural integration for convergence holding, given its proven anatomic connections with the central mesencephalic reticular formation and C-group medial rectus motoneurons in the oculomotor nucleus, which project to extraocular muscle nontwitch fibers specialized for fatigue-resistant, slow, tonic activity such as vergence holding. NEW & NOTEWORTHY Supranuclear control of the near-vision response has been incompletely understood to date. We propose, based on clinical and anatomic evidence, functional pathways for vergence that participate in the generation of the near triad, “slow vergence,” and vergence holding.

Central mesencephalic reticular formation control of the near response: lens accommodation circuits

To view a nearby target, the three components of the near response are brought into play: 1) the eyes are converged through contraction of the medial rectus muscles to direct both foveae at the target, 2) the ciliary muscle contracts to allow the lens to thicken, increasing its refractive power to focus the near target on the retina, and 3) the pupil constricts to increase depth of field. In this study, we utilized retrograde transsynaptic transport of the N2c strain of rabies virus injected into the ciliary body of one eye of macaque monkeys to identify premotor neurons that control lens accommodation. We previously used this approach to label a premotor population located in the supraoculomotor area. In the present report, we describe a set of neurons located bilaterally in the central mesencephalic reticular formation that are labeled in the same time frame as the supraoculomotor area population, indicating their premotor character. The labeled premotor neurons are mostly multipolar cells, with long, very sparsely branched dendrites. They form a band that stretches across the core of the midbrain reticular formation. This population appears to be continuous with the premotor near-response neurons located in the supraoculomotor area at the level of the caudal central subdivision of the oculomotor nucleus. The central mesencephalic reticular formation has previously been associated with horizontal saccadic eye movements, so these premotor cells might be involved in controlling lens accommodation during disjunctive saccades. Alternatively, they may represent a population that controls vergence velocity. NEW & NOTEWORTHY This report uses transsynaptic transport of rabies virus to provide new evidence that the central mesencephalic reticular formation (cMRF) contains premotor neurons controlling lens accommodation. When combined with other recent reports that the cMRF also contains premotor neurons supplying medial rectus motoneurons, these results indicate that this portion of the reticular formation plays an important role in directing the near response and disjunctive saccades when viewers look between targets located at different distances.