Assessing locomotory rate in response to food for the identification of neuronal and muscular defects in C. elegans.

C. elegans is a bacteria-eating soil-dwelling nematode. Typical cultivation of laboratory-reared populations occurs on bacteria-covered solid media, where they move along with sinusoidal undulations. Nematodes decelerate when they encounter food. Dopaminergic and serotonergic neurotransmission regulate this behavior. Here, we describe the procedure for determining food-dependent locomotion rate of fed and fasting nematodes. We detail steps for assay plate preparation, C. elegans synchronization, and assessment of locomotion. The behaviors we describe provide information regarding the animal's physiological neuronal and muscular function. For complete details on the use and execution of this protocol, please refer to Petratou et al. (2023)1 and Sawin et al. (2000).2.

A proton-inhibited DEG/ENaC ion channel maintains neuronal ionstasis and promotes neuronal survival under stress.

The nervous system participates in the initiation and modulation of systemic stress. Ionstasis is of utmost importance for neuronal function. Imbalance in neuronal sodium homeostasis is associated with pathologies of the nervous system. However, the effects of stress on neuronal Na+ homeostasis, excitability, and survival remain unclear. We report that the DEG/ENaC family member DEL-4 assembles into a proton-inactivated sodium channel. DEL-4 operates at the neuronal membrane and synapse to modulate Caenorhabditis elegans locomotion. Heat stress and starvation alter DEL-4 expression, which in turn alters the expression and activity of key stress-response transcription factors and triggers appropriate motor adaptations. Similar to heat stress and starvation, DEL-4 deficiency causes hyperpolarization of dopaminergic neurons and affects neurotransmission. Using humanized models of neurodegenerative diseases in C. elegans, we showed that DEL-4 promotes neuronal survival. Our findings provide insights into the molecular mechanisms by which sodium channels promote neuronal function and adaptation under stress.

Molecular Interventions towards Multiple Sclerosis Treatment.

Multiple sclerosis (MS) is an autoimmune life-threatening disease, afflicting millions of people worldwide. Although the disease is non-curable, considerable therapeutic advances have been achieved through molecular immunotherapeutic approaches, such as peptides vaccination, administration of monoclonal antibodies, and immunogenic copolymers. The main aims of these therapeutic strategies are to shift the MS-related autoimmune response towards a non-inflammatory T helper 2 (Th2) cells response, inactivate or ameliorate cytotoxic autoreactive T cells, induce secretion of anti-inflammatory cytokines, and inhibit recruitment of autoreactive lymphocytes to the central nervous system (CNS). These approaches can efficiently treat autoimmune encephalomyelitis (EAE), an essential system to study MS in animals, but they can only partially inhibit disease progress in humans. Nevertheless, modern immunotherapeutic techniques remain the most promising tools for the development of safe MS treatments, specifically targeting the cellular factors that trigger the initiation of the disease.

Multimodal sensory processing in Caenorhabditis elegans.

Multisensory integration is a mechanism that allows organisms to simultaneously sense and understand external stimuli from different modalities. These distinct signals are transduced into neuronal signals that converge into decision-making neuronal entities. Such decision-making centres receive information through neuromodulators regarding the organism's physiological state and accordingly trigger behavioural responses. Despite the importance of multisensory integration for efficient functioning of the nervous system, and also the implication of dysfunctional multisensory integration in the aetiology of neuropsychiatric disease, little is known about the relative molecular mechanisms. Caenorhabditis elegans is an appropriate model system to study such mechanisms and elucidate the molecular ways through which organisms understand external environments in an accurate and coherent fashion.

Longevity pathways and memory aging.

The aging process has been associated with numerous pathologies at the cellular, tissue, and organ level. Decline or loss of brain functions, including learning and memory, is one of the most devastating and feared aspects of aging. Learning and memory are fundamental processes by which animals adjust to environmental changes, evaluate various sensory signals based on context and experience, and make decisions to generate adaptive behaviors. Age-related memory impairment is an important phenotype of brain aging. Understanding the molecular mechanisms underlying age-related memory impairment is crucial for the development of therapeutic strategies that may eventually lead to the development of drugs to combat memory loss. Studies in invertebrate animal models have taught us much about the physiology of aging and its effects on learning and memory. In this review we survey recent progress relevant to conserved molecular pathways implicated in both aging and memory formation and consolidation.

Small-aperture monovision and the Pulfrich experience: absence of neural adaptation effects.

PURPOSE: To explore whether adaptation reduces the interocular visual latency differences and the induced Pulfrich effect caused by the anisocoria implicit in small-aperture monovision. METHODS: Anisocoric vision was simulated in two adults by wearing in the non-dominant eye for 7 successive days, while awake, an opaque soft contact lens (CL) with a small, central, circular aperture. This was repeated with aperture diameters of 1.5 and 2.5 mm. Each day, monocular and binocular pattern-reversal Visual Evoked Potentials (VEP) were recorded. Additionally, the Pulfrich effect was measured: the task of the subject was to state whether a a 2-deg spot appeared in front or behind the plane of a central cross when moved left-to-right or right-to-left on a display screen. The retinal illuminance of the dominant eye was varied using neutral density (ND) filters to establish the ND value which eliminated the Pulfrich effect for each lens. All experiments were performed at luminance levels of 5 and 30 cd/m(2). RESULTS: Interocular differences in monocular VEP latency (at 30 cd/m(2)) rose to about 12-15 ms and 20-25 ms when the CL aperture was 2.5 and 1.5 mm, respectively. The effect was more pronounced at 5 cd/m(2) (i.e. with larger natural pupils). A strong Pulfrich effect was observed under all conditions, with the effect being less striking for the 2.5 mm aperture. No neural adaptation appeared to occur: neither the interocular differences in VEP latency nor the ND value required to null the Pulfrich effect reduced over each 7-day period of anisocoric vision. CONCLUSIONS: Small-aperture monovision produced marked interocular differences in visual latency and a Pulfrich experience. These were not reduced by adaptation, perhaps because the natural pupil diameter of the dominant eye was continually changing throughout the day due to varying illumination and other factors, making adaptation difficult.

Interocular differences in visual latency induced by reduced-aperture monovision.

PURPOSE: To explore the interocular differences in the temporal responses of the eyes induced by the monocular use of small-aperture optics designed to aid presbyopes by increasing their depth-of-focus. METHODS: Monocular and binocular pattern-reversal visual evoked potentials (VEPs) were measured at a mean photopic field luminance of 30 cd/m(2) in seven normal subjects with either natural pupils or when the non-dominant eye wore a small-aperture contact lens (aperture diameter 1.5, 2.5 or 3.5 mm, or an annular opaque stop of inner and outer diameters 1.5 and 4.0 mm respectively). Responses were also measured with varying stimulus luminance (5, 13.9, 27.2 and 45 cd/m(2)) and a fixed 3.0 mm artificial pupil. RESULTS: Mean natural pupil diameters were 4.7 and 4.4 mm under monocular and binocular conditions respectively. The small-aperture contact lenses reduced the amplitude of the P100 component of the VEP and increased its latency. Inter-ocular differences in latency rose to about 20-25 ms when the pupil diameter of the non-dominant eye was reduced to 1.5 mm. The measurements with fixed pupil and varying luminance suggested that the observed effects were explicable in terms of the changes in retinal illuminance produced by the restrictions in pupil area. CONCLUSIONS: The anisocoria induced by small-aperture approaches to aid presbyopes produces marked interocular differences in visual latency. The literature of the Pulfrich effect suggests that such differences can lead to distortions in the perception of relative movement and, in some cases, to possible hazard.

Binocular summation improves performance to defocus-induced blur.

PURPOSE: To assess whether there are any advantages of binocular over monocular vision under blur conditions. METHODS: The effect of defocus, induced by positive lenses, was measured on the pattern reversal visual evoked potential (VEP) and on visual acuity (VA). Monocular (dominant eye) and binocular VEPs were recorded from 13 volunteers (average age, 28 ± 5 years; average spherical equivalent, -0.25 ± 0.73 D) for defocus up to 2.00 D using positive powered lenses. VEPs were elicited using reversing 10 arcmin checks (4 reversals/s). The stimulus subtended a circular field of 7° with 100% contrast and mean luminance 30 cd/m(2). VA was measured under the same conditions using ETDRS charts. All measurements were performed at 1 m viewing distance with best spectacle sphero-cylindrical correction and natural pupils. RESULTS: With binocular stimulation, amplitudes and implicit times of the P100 component of the VEPs were greater and shorter, respectively, in all cases than for monocular stimulation. Mean binocular enhancement ratio in the P100 amplitude was 2.1 in focus, increasing linearly with defocus to be 3.1 at +2.00 D defocus. Mean peak latency was 2.9 ms shorter in focus with binocular than for monocular stimulation, with the difference increasing with defocus to 8.8 ms at +2.00 D. As for the VEP amplitude, VA was always better with binocular than with monocular vision, with the difference being greater for higher retinal blur. CONCLUSIONS: Both subjective and electrophysiological results show that binocular vision ameliorates the effect of defocus. The increased binocular facilitation observed with retinal blur may be due to the activation of a larger population of neurons at close-to-threshold detection under binocular stimulation.