scholarly journals Timing Determines Tuning: a Rapid Spatiotemporal Transformation in Superior Colliculus Neurons During Reactive Gaze Shifts

2018 ◽  
Author(s):  
Morteza Sadeh ◽  
Amirsaman Sajad ◽  
Hongying Wang ◽  
Xiaogang Yan ◽  
John Douglas Crawford
Keyword(s):  
Superior Colliculus ◽  
Motor Neurons ◽  
Neural Control ◽  
Model Fitting ◽  
Quantitative Measure ◽  
Cell Types ◽  
Gaze Behavior ◽  
Motor Responses ◽  
Visuomotor Transformations ◽  
Gaze Saccades

AbstractGaze saccades –rapid shifts of the eyes and head toward a goal— have provided fundamental insights into the neural control of movement. For example, it has been shown that the superior colliculus (SC) transforms a visual target (T) code to future gaze (G) location commands after a memory delay. However, this transformation has not been observed in ‘reactive’ saccades made directly to a stimulus, so its contribution to normal gaze behavior is unclear. Here, we tested this using a quantitative measure of the spatial continuum between T and G coding based on variable gaze errors. We demonstrate that a rapid T-G transformation occurs between SC visual and motor responses during reactive saccades, even within visuomotor cells, with a continuous spatiotemporal shift in coding occurring in cell types (visual, visuomotor, motor). We further show that the primary determinant of this spatial code was not the intrinsic visual-motor index of different cells or populations, but rather the timing of the response in all cells. These results suggest that the SC provides a rapid spatiotemporal transformation for normal gaze saccades, that its motor responses contribute to variable gaze errors, and that those errors arise from a noisy spatiotemporal transformation involving all SC neurons.Significance StatementOculomotor studies have demonstrated visuomotor transformations in structures like the superior colliculus with the use of trained behavioral manipulations, like the memory delay and antisaccades tasks, but it is not known how this happens during normal saccades. Here, using a spatiotemporal model fitting method based on endogenous gaze errors in ‘reactive’ gaze saccades, we show that the superior colliculus provides a rapid spatiotemporal transformation from target to gaze coding that involves visual, visuomotor, and motor neurons. This technique demonstrates that SC spatial codes are not fixed, and may provide a quantitative biomarker for assessing the health of sensorimotor transformations.

Neural control of gut homeostasis

2020 ◽  
Vol 319 (6) ◽  
pp. G718-G732
Author(s):  
Nasser Abdullah ◽  
Manon Defaye ◽  
Christophe Altier
Keyword(s):  
Dorsal Root Ganglia ◽  
Motor Neurons ◽  
Immune Cells ◽  
Dorsal Root ◽  
Neural Control ◽  
Cell Types ◽  
Nodose Ganglia ◽  
Gut Homeostasis ◽  
Large Populations ◽  
Higher Cognitive Functions

The gut-brain axis is a coordinated communication system that not only maintains homeostasis, but significantly influences higher cognitive functions and emotions, as well as neurological and behavioral disorders. Among the large populations of sensory and motor neurons that innervate the gut, insights into the function of primary afferent nociceptors, whose cell bodies reside in the dorsal root ganglia and nodose ganglia, have revealed their multiple crosstalk with several cell types within the gut wall, including epithelial, vascular, and immune cells. These bidirectional communications have immunoregulatory functions, control host response to pathogens, and modulate sensations associated with gastrointestinal disorders, through activation of immune cells and glia in the peripheral and central nervous system, respectively. Here, we will review the cellular and neurochemical basis of these interactions at the periphery, in dorsal root ganglia, and in the spinal cord. We will discuss the research gaps that should be addressed to get a better understanding of the multifunctional role of sensory neurons in maintaining gut homeostasis and regulating visceral sensitivity.

Spatial Relationships of Visuomotor Transformations in the Superior Colliculus Map

2008 ◽  
Vol 100 (5) ◽  
pp. 2564-2576 ◽  
Author(s):  
Robert A. Marino ◽  
C. Kip Rodgers ◽  
Ron Levy ◽  
Douglas P. Munoz
Keyword(s):  
Visual Field ◽  
Superior Colliculus ◽  
Visual Information ◽  
Visual Space ◽  
Motor Command ◽  
Spatial Relationships ◽  
Visual Response ◽  
Motor Responses ◽  
Visuomotor Transformations ◽  
Command Signals

The oculomotor system is well understood compared with other motor systems; however, we do not yet know the spatial details of sensory to motor transformations. This study addresses this issue by quantifying the spatial relationships between visual and motor responses in the superior colliculus (SC), a midbrain structure involved in the transformation of visual information into saccadic motor command signals. We collected extracellular single-unit recordings from 150 visual-motor (VM) and 28 motor (M) neurons in two monkeys trained to perform a nonpredictive visually guided saccade task to 110 possible target locations. Motor related discharge was greater than visual related discharge in 94% (141/150) of the VM neurons. Across the population of VM neurons, the mean locations of the peak visual and motor responses were spatially aligned. The visual response fields (RFs) were significantly smaller than and usually contained within the motor RFs. Converting RFs into the SC coordinate system significantly reduced any misalignment between peak visual and motor locations. RF size increased with increasing eccentricity in visual space but remained invariant on the SC map beyond 1 mm of the rostral pole. RF shape was significantly more symmetric in SC map coordinates compared with visual space coordinates. These results demonstrate that VM neurons specify the same location of a target stimulus in the visual field as the intended location of an upcoming saccade with minimal misalignment to downstream structures. The computational consequences of spatially transforming visual field coordinates to the SC map resulted in increased alignment and spatial symmetry during visual-sensory to saccadic-motor transformations.

scholarly journals Interleukin-17 and Th17 Lymphocytes Directly Impair Motoneuron Survival of Wildtype and FUS-ALS Mutant Human iPSCs

2021 ◽  
Vol 22 (15) ◽  
pp. 8042
Author(s):  
Mengmeng Jin ◽  
Katja Akgün ◽  
Tjalf Ziemssen ◽  
Markus Kipp ◽  
Rene Günther ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Th17 Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Positive Control ◽  
Interleukin 17 ◽  
Fused In Sarcoma ◽  
Th17 Lymphocytes ◽  
Human Ipscs ◽  
Als Patients

Amyotrophic lateral sclerosis (ALS) is a progressive disease leading to the degeneration of motor neurons (MNs). Neuroinflammation is involved in the pathogenesis of ALS; however, interactions of specific immune cell types and MNs are not well studied. We recently found a shift toward T helper (Th)1/Th17 cell-mediated, pro-inflammatory immune responses in the peripheral immune system of ALS patients, which positively correlated with disease severity and progression. Whether Th17 cells or their central mediator, Interleukin-17 (IL-17), directly affects human motor neuron survival is currently unknown. Here, we evaluated the contribution of Th17 cells and IL-17 on MN degeneration using the co-culture of iPSC-derived MNs of fused in sarcoma (FUS)-ALS patients and isogenic controls with Th17 lymphocytes derived from ALS patients, healthy controls, and multiple sclerosis (MS) patients (positive control). Only Th17 cells from MS patients induced severe MN degeneration in FUS-ALS as well as in wildtype MNs. Their main effector, IL-17A, yielded in a dose-dependent decline of the viability and neurite length of MNs. Surprisingly, IL-17F did not influence MNs. Importantly, neutralizing IL-17A and anti-IL-17 receptor A treatment reverted all effects of IL-17A. Our results offer compelling evidence that Th17 cells and IL-17A do directly contribute to MN degeneration.

scholarly journals The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration

2020 ◽  
Author(s):  
Paymaan Jafar-nejad ◽  
Berit Powers ◽  
Armand Soriano ◽  
Hien Zhao ◽  
Daniel A Norris ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Cell Types ◽  
Rnase H ◽  
Central Administration ◽  
Spinal Motor Neurons ◽  
New Class ◽  
Wide Range ◽  
Therapeutic Development

Abstract Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.

scholarly journals Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy

2021 ◽  
Vol 22 (6) ◽  
pp. 3007
Author(s):  
Isabel Lastres-Becker ◽  
Gracia Porras ◽  
Marina Arribas-Blázquez ◽  
Inés Maestro ◽  
Daniel Borrego-Hernández ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Autophagic Flux ◽  
Metabolic Disturbances ◽  
Molecular Alterations ◽  
Healthy Donors ◽  
Inflammatory Profile ◽  
Als Patients

Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition where motor neurons (MNs) degenerate. Most of the ALS cases are sporadic (sALS), whereas 10% are hereditarily transmitted (fALS), among which mutations are found in the gene that codes for the enzyme superoxide dismutase 1 (SOD1). A central question in ALS field is whether causative mutations display selective alterations not found in sALS patients, or they converge on shared molecular pathways. To identify specific and common mechanisms for designing appropriate therapeutic interventions, we focused on the SOD1-mutated (SOD1-ALS) versus sALS patients. Since ALS pathology involves different cell types other than MNs, we generated lymphoblastoid cell lines (LCLs) from sALS and SOD1-ALS patients and healthy donors and investigated whether they show changes in oxidative stress, mitochondrial dysfunction, metabolic disturbances, the antioxidant NRF2 pathway, inflammatory profile, and autophagic flux. Both oxidative phosphorylation and glycolysis appear to be upregulated in lymphoblasts from sALS and SOD1-ALS. Our results indicate significant differences in NRF2/ARE pathway between sALS and SOD1-ALS lymphoblasts. Furthermore, levels of inflammatory cytokines and autophagic flux discriminate between sALS and SOD1-ALS lymphoblasts. Overall, different molecular mechanisms are involved in sALS and SOD1-ALS patients and thus, personalized medicine should be developed for each case.

scholarly journals Perception and Action under Different Stimulus Presentations: A Review of Eye-Tracking Studies with an Extended View on Possibilities of Virtual Reality

2021 ◽  
Vol 11 (12) ◽  
pp. 5546
Author(s):  
Florian Heilmann ◽  
Kerstin Witte
Keyword(s):  
Virtual Reality ◽  
Eye Tracking ◽  
Literature Search ◽  
Perception And Action ◽  
Stimulus Presentation ◽  
Gaze Behavior ◽  
Motor Responses ◽  
Scientific Approach ◽  
Extended View

Visual anticipation is essential for performance in sports. This review provides information on the differences between stimulus presentations and motor responses in eye-tracking studies and considers virtual reality (VR), a new possibility to present stimuli. A systematic literature search on PubMed, ScienceDirect, IEEE Xplore, and SURF was conducted. The number of studies examining the influence of stimulus presentation (in situ, video) is deficient but still sufficient to describe differences in gaze behavior. The seven reviewed studies indicate that stimulus presentations can cause differences in gaze behavior. Further research should focus on displaying game situations via VR. The advantages of a scientific approach using VR are experimental control and repeatability. In addition, game situations could be standardized and movement responses could be included in the analysis.

scholarly journals Establishment of a Human Induced Pluripotent Stem Cell-Derived Neuromuscular Co-Culture Under Optogenetic Control

2020 ◽  
Author(s):  
Elliot W. Swartz ◽  
Greg Shintani ◽  
Jijun Wan ◽  
Joseph S. Maffei ◽  
Sarah H. Wang ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Calcium Flux ◽  
Electrode Arrays ◽  
Spinal Motor Neurons ◽  
Culture Model ◽  
Skeletal Myotubes ◽  
Induced Pluripotent

SummaryThe failure of the neuromuscular junction (NMJ) is a key component of degenerative neuromuscular disease, yet how NMJs degenerate in disease is unclear. Human induced pluripotent stem cells (hiPSCs) offer the ability to model disease via differentiation toward affected cell types, however, the re-creation of an in vitro neuromuscular system has proven challenging. Here we present a scalable, all-hiPSC-derived co-culture system composed of independently derived spinal motor neurons (MNs) and skeletal myotubes (sKM). In a model of C9orf72-associated disease, co-cultures form functional NMJs that can be manipulated through optical stimulation, eliciting muscle contraction and measurable calcium flux in innervated sKM. Furthermore, co-cultures grown on multi-electrode arrays (MEAs) permit the pharmacological interrogation of neuromuscular physiology. Utilization of this co-culture model as a tunable, patient-derived system may offer significant insights into NMJ formation, maturation, repair, or pathogenic mechanisms that underlie NMJ dysfunction in disease.

scholarly journals The influence of temporal predictability on express visuomotor responses

2020 ◽  
Author(s):  
Samuele Contemori ◽  
Gerald E. Loeb ◽  
Brian D. Corneil ◽  
Guy Wallis ◽  
Timothy J. Carroll
Keyword(s):  
Superior Colliculus ◽  
Onset Time ◽  
Surface Emg ◽  
Stimulus Onset ◽  
Target Motion ◽  
Target Velocity ◽  
Moving Target ◽  
Visuomotor Transformations ◽  
Shoulder Muscles ◽  
Temporal Predictability

ABSTRACTVolitional visuomotor responses in humans are generally thought to manifest 100ms or more after stimulus onset. Under appropriate conditions, however, much faster target-directed responses can be produced at upper limb and neck muscles. These “express” responses have been termed stimulus-locked responses (SLRs) and are proposed to be modulated by visuomotor transformations performed subcortically via the superior colliculus. Unfortunately, for those interested in studying SLRs, these responses have proven difficult to detect consistently across individuals. The recent report of an effective paradigm for generating SLRs in 100% of participants appears to change this. The task required the interception of a moving target that emerged from behind a barrier at a time consistent with the target velocity. Here we aimed to reproduce the efficacy of this paradigm for eliciting SLRs and to test the hypothesis that its effectiveness derives from the predictability of target onset time as opposed to target motion per se. In one experiment, we recorded surface EMG from shoulder muscles as participants made reaches to intercept temporally predictable or unpredictable targets. Consistent with our hypothesis, predictably timed targets produced more frequent and stronger SLRs than unpredictably timed targets. In a second experiment, we compared different temporally predictable stimuli and observed that transiently presented targets produced larger and earlier SLRs than sustained moving targets. Our results suggest that target motion is not critical for facilitating the expression of an SLR and that timing predictability does not rely on extrapolation of a physically plausible motion trajectory. These findings provide support for a mechanism whereby an internal timer, probably located in cerebral cortex, primes the processing of both visual input and motor output within the superior colliculus to produce SLRs.

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