Frontiers in Neural Circuits最新文献

Introduction: Space Motion Sickness (SMS) is a syndrome that affects around 70% of astronauts and includes symptoms of nausea, dizziness, fatigue, vertigo, headaches, vomiting, and cold sweating. Consequences range from discomfort to severe sensorimotor and cognitive incapacitation, which might cause potential problems for mission-critical tasks and astronauts and cosmonauts' well-being. Both pharmacological and non-pharmacological countermeasures have been proposed to mitigate SMS. However, their effectiveness has not been systematically evaluated. Here we present the first systematic review of published peer-reviewed research on the effectiveness of pharmacological and non-pharmacological countermeasures to SMS.

Methods: We performed a double-blind title and abstract screening using the online Rayyan collaboration tool for systematic reviews, followed by a full-text screening. Eventually, only 23 peer-reviewed studies underwent data extraction.

Results: Both pharmacological and non-pharmacological countermeasures can help mitigate SMS symptoms.

Discussion: No definitive recommendation can be given regarding the superiority of any particular countermeasure approach. Importantly, there is considerable heterogeneity in the published research methods, lack of a standardized assessment approach, and small sample sizes. To allow for consistent comparisons between SMS countermeasures in the future, standardized testing protocols for spaceflight and ground-based analogs are needed. We believe that the data should be made openly available, given the uniqueness of the environment in which it is collected.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021244131.

Since the early 1900's it has been known that a neural network, situated entirely within the spinal cord, is capable of generating the movements required for coordinated locomotion in limbed vertebrates. Due the number of interneurons in the spinal cord, and the extent to which neurons with the same function are intermingled with others that have divergent functions, the components of this neural circuit (now referred to as the locomotor central pattern generator-CPG) have long proven to be difficult to identify. Over the past 20 years a molecular approach has been incorporated to study the locomotor CPG. This approach has resulted in new information regarding the identity of its component interneurons, and their specific role during locomotor activity. In this mini review the role of the inhibitory interneuronal populations that have been shown to be involved in locomotor activity are described, and their specific role in securing left-right, and flexor extensor alternation is outlined. Understanding how these interneuronal populations are activated, modulated, and interact with one another will help us understand how locomotor behavior is produced. In addition, a deeper understanding of the structure and mechanism of function of the locomotor CPG has the potential to assist those developing strategies aimed at enhancing recovery of motor function in spinal cord injured patients.

Flexible orientation through any environment requires a sense of current relative heading that is updated based on self-motion. Global external cues originating from the sky or the earth's magnetic field and local cues provide a reference frame for the sense of direction. Locally, optic flow may inform about turning maneuvers, travel speed and covered distance. The central complex in the insect brain is associated with orientation behavior and largely acts as a navigation center. Visual information from global celestial cues and local landmarks are integrated in the central complex to form an internal representation of current heading. However, it is less clear how optic flow is integrated into the central-complex network. We recorded intracellularly from neurons in the locust central complex while presenting lateral grating patterns that simulated translational and rotational motion to identify these sites of integration. Certain types of central-complex neurons were sensitive to optic-flow stimulation independent of the type and direction of simulated motion. Columnar neurons innervating the noduli, paired central-complex substructures, were tuned to the direction of simulated horizontal turns. Modeling the connectivity of these neurons with a system of proposed compass neurons can account for rotation-direction specific shifts in the activity profile in the central complex corresponding to turn direction. Our model is similar but not identical to the mechanisms proposed for angular velocity integration in the navigation compass of the fly Drosophila.

Alzheimer's disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity. This excessive electrical activity contributes to dysregulated neural network function and synaptic damage. Mechanistically, evidence suggests that hyperexcitability accelerates production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute to neural network impairment and synapse loss. This review focuses on the pathways and molecular changes that cause hyperexcitability and how RNS-dependent posttranslational modifications, represented predominantly by protein S-nitrosylation, mediate, at least in part, the deleterious effects of hyperexcitability on single neurons and the neural network, resulting in synaptic loss in AD.

Introduction: Spinal cord injury (SCI) is a debilitating condition that disrupts the communication between the brain and the spinal cord. Several studies have sought to determine how to revive dormant spinal circuits caudal to the lesion to restore movements in paralyzed patients. So far, recovery levels in human patients have been modest at best. In contrast, animal models of SCI exhibit more recovery of lost function. Previous work from our lab has identified dI3 interneurons as a spinal neuron population central to the recovery of locomotor function in spinalized mice. We seek to determine the changes in the circuitry of dI3 interneurons and motoneurons following SCI in adult mice.

Methods: After a complete transection of the spinal cord at T9-T11 level in transgenic Isl1:YFP mice and subsequent treadmill training at various time points of recovery following surgery, we examined changes in three key circuits involving dI3 interneurons and motoneurons: (1) Sensory inputs from proprioceptive and cutaneous afferents, (2) Presynaptic inhibition of sensory inputs, and (3) Central excitatory glutamatergic synapses from spinal neurons onto dI3 INs and motoneurons. Furthermore, we examined the possible role of treadmill training on changes in synaptic connectivity to dI3 interneurons and motoneurons.

Results: Our data suggests that VGLUT1⁺ inputs to dI3 interneurons decrease transiently or only at later stages after injury, whereas levels of VGLUT1⁺ remain the same for motoneurons after injury. Levels of VGLUT2⁺ inputs to dI3 INs and MNs may show transient increases but fall below levels seen in sham-operated mice after a period of time. Levels of presynaptic inhibition to VGLUT1⁺ inputs to dI3 INs and MNs can rise shortly after SCI, but those increases do not persist. However, levels of presynaptic inhibition to VGLUT1⁺ inputs never fell below levels observed in sham-operated mice. For some synaptic inputs studied, levels were higher in spinal cord-injured animals that received treadmill training, but these increases were observed only at some time points.

Discussion: These results suggest remodeling of spinal circuits involving spinal interneurons that have previously been implicated in the recovery of locomotor function after spinal cord injury in mice.

The brain creates a single visual percept of the world with inputs from two eyes. This means that downstream structures must integrate information from the two eyes coherently. Not only does the brain meet this challenge effortlessly, it also uses small differences between the two eyes' inputs, i.e., binocular disparity, to construct depth information in a perceptual process called stereopsis. Recent studies have advanced our understanding of the neural circuits underlying stereoscopic vision and its development. Here, we review these advances in the context of three binocular properties that have been most commonly studied for visual cortical neurons: ocular dominance of response magnitude, interocular matching of orientation preference, and response selectivity for binocular disparity. By focusing mostly on mouse studies, as well as recent studies using ferrets and tree shrews, we highlight unresolved controversies and significant knowledge gaps regarding the neural circuits underlying binocular vision. We note that in most ocular dominance studies, only monocular stimulations are used, which could lead to a mischaracterization of binocularity. On the other hand, much remains unknown regarding the circuit basis of interocular matching and disparity selectivity and its development. We conclude by outlining opportunities for future studies on the neural circuits and functional development of binocular integration in the early visual system.

The cerebral cortex innervates motor neurons in the anterior horn of the spinal cord by regulating of interneurons. At present, nerve tracing, immunohistochemistry, and immunoelectron microscopy are used to explore and confirm the characteristics of synaptic connections between the corticospinal tract (CST) and cervical spinal calretinin (Cr) interneurons. Our morphological results revealed that (1) biotinylated dextran amine labeled (BDA+) fibers from the cerebral cortex primarily presented a contralateral spinal distribution, with a denser distribution in the ventral horn (VH) than in the dorsal horn (DH). An electron microscope (EM) showed that BDA+ terminals formed asymmetric synapses with spinal neurons, and their mean labeling rate was not different between the DH and VH. (2) Cr-immunoreactive (Cr+) neurons were unevenly distributed throughout the spinal gray matter, and were denser and larger in the VH than in the DH. At the single labeling electron microscope (EM) level, the labeling rate of Cr+ dendrites was higher in the VH than in the DH, in which Cr+ dendrites mainly received asymmetric synaptic inputs, and between the VH and DH. (3) Immunofluorescence triple labeling showed obvious apposition points among BDA+ terminals, synaptophysin and Cr+ dendrites, with a higher density in the VH than in the DH. (4) Double labeling in EM, BDA+ terminals and Cr+ dendrites presented the same pattern, BDA+ terminals formed asymmetric synapses either with Cr+ dendrites or Cr negative (Cr-) dendrites, and Cr+ dendrites received either BDA+ terminals or BDA- synaptic inputs. The average percentage of BDA+ terminals targeting Cr+ dendrites was higher in the VH than in the DH, but the percentage of BDA+ terminals targeting Cr- dendrites was prominently higher than that targeting Cr+ dendrites. There was no difference in BDA+ terminal size. The percentage rate for Cr+ dendrites receiving BDA+ terminal inputs was lower than that receiving BDA- terminal inputs, and the BDA+ terminal size was larger than the BDA- terminal size received by Cr+ dendrites. The present morphological results suggested that spinal Cr+ interneurons are involved in the regulatory process of the cortico-spinal pathway.

Memories associated to signals have been proven to rely on the recruitment of associative memory neurons that are featured by mutual synapse innervations among cross-modal cortices. Whether the consolidation of associative memory is endorsed by the upregulation of associative memory neurons in an intramodal cortex remains to be examined. The function and interconnection of associative memory neurons were investigated by in vivo electrophysiology and adeno-associated virus-mediated neural tracing in those mice that experienced associative learning by pairing the whisker tactile signal and the olfactory signal. Our results show that odorant-induced whisker motion as a type of associative memory is coupled with the enhancement of whisking-induced whisker motion. In addition to some barrel cortical neurons encoding both whisker and olfactory signals, i.e., their recruitment as associative memory neurons, the synapse interconnection and spike-encoding capacity of associative memory neurons within the barrel cortex are upregulated. These upregulated alternations were partially observed in the activity-induced sensitization. In summary, associative memory is mechanistically based on the recruitment of associative memory neurons and the upregulation of their interactions in intramodal cortices.

Transitioning between gravitational environments results in a central reinterpretation of sensory information, producing an adapted sensorimotor state suitable for motor actions and perceptions in the new environment. Critically, this central adaptation is not instantaneous, and complete adaptation may require weeks of prolonged exposure to novel environments. To mitigate risks associated with the lagging time course of adaptation (e.g., spatial orientation misperceptions, alterations in locomotor and postural control, and motion sickness), it is critical that we better understand sensorimotor states during adaptation. Recently, efforts have emerged to model human perception of orientation and self-motion during sensorimotor adaptation to new gravity stimuli. While these nascent computational frameworks are well suited for modeling exposure to novel gravitational stimuli, they have yet to distinguish how the central nervous system (CNS) reinterprets sensory information from familiar environmental stimuli (i.e., readaptation). Here, we present a theoretical framework and resulting computational model of vestibular adaptation to gravity transitions which captures the role of implicit memory. This advancement enables faster readaptation to familiar gravitational stimuli, which has been observed in repeat flyers, by considering vestibular signals dependent on the new gravity environment, through Bayesian inference. The evolution and weighting of hypotheses considered by the CNS is modeled via a Rao-Blackwellized particle filter algorithm. Sensorimotor adaptation learning is facilitated by retaining a memory of past harmonious states, represented by a conditional state transition probability density function, which allows the model to consider previously experienced gravity levels (while also dynamically learning new states) when formulating new alternative hypotheses of gravity. In order to demonstrate our theoretical framework and motivate future experiments, we perform a variety of simulations. These simulations demonstrate the effectiveness of this model and its potential to advance our understanding of transitory states during which central reinterpretation occurs, ultimately mitigating the risks associated with the lagging time course of adaptation to gravitational environments.