Biology subjects

Morquette, P.

Publications and source records attributed to Morquette, P..

3 recordsLinked to original sources

bioRxiv2026

Minimal Mimics and Maps of Natural Light for Mammals

Light drives processes that include perception and the regulation of circadian rhythms, sleep, metabolism, and development. These processes are initiated by photopigment molecules, each preferentially absorbing particular wavelengths. Light of a given spectrum stimulates an animals set of photopigments in a specific profile. Natural skylight and its variations produce stimulation profiles that promote normal physiology. To mimic these profiles using artificial light, we consider the thermally stable, photoconvertible states of relevant photopigments: ground states of rhodopsin and cone photopigments, and three states of melanopsin. This gives a relatively high-dimensional representation of illumination. Nevertheless, we find that two wavelengths suffice to closely mimic the effects of natural light for mammals, including humans and mice. Adjusting the wavelength ratio allows mimicry of natural lights variations, such as those from twilight to noon. Ratio adjustments also compensate for lights filtering by elements like the eyes optics and laboratory cages. Adding a third wavelength makes natural light mimicry nearly perfect. By contrast, common artificial lighting--designed for low-dimensional, human color space--stimulates photopigments in unnatural proportions. We conclude by providing species-specific maps of photopigment stimulation profiles under natural and artificial illumination, which make our observations intuitive while providing insight into the diverse visual ecologies of mammals. SIGNIFICANCE STATEMENTHumans sense light for vital processes like sight and physiological regulation. These processes are normal under natural skylight, where they evolved. However, much of modern life is spent in artificial light, which is unlike natural light in many of its biological effects. This disparity has been linked to disorders that range from cardiovascular disease to cancer. This manuscript introduces simple forms of artificial lighting that replicate the effects of natural skylight on photoreceptors of humans and other species. It also demonstrates how the biological effects of natural and artificial lights can be captured in simple maps, facilitating the choice and further design of illumination that is beneficial.

neuroscience↗

bioRxiv2024

Loss of SARM1 protects against retinal ganglion cell degeneration in Autosomal Dominant Optic Atrophy

Autosomal Dominant Optic Atrophy (ADOA), the most prevalent inherited optic neuropathy, leads to retinal ganglion cell (RGC) degeneration and vision loss. ADOA is primarily caused by mutations in the OPA1 gene, which encodes a conserved GTPase important for mitochondrial inner membrane dynamics. To date, the disease mechanism remains unclear, and no therapies are available. Here, we present a novel mouse model carrying the pathogenic Opa1R290Q/+ allele that recapitulates key features of human ADOA, including mitochondrial defects, age-related RGC loss, optic nerve degeneration, and reduced RGC functions. We identify SARM1, a neurodegeneration switch, as a key driver of RGC degeneration in these mice. Sarm1 knockout nearly completely suppresses all the degeneration phenotypes. Additionally, we show that SARM1 is located within the mitochondrial intermembrane space (IMS). These findings indicate that SARM1 is activated downstream of mitochondrial dysfunction in ADOA, highlighting it as a promising therapeutic target.

neuroscience↗

bioRxiv2024

Astrocyte-induced firing in primary afferent axons

The mesencephalic trigeminal nucleus is unique in that it contains the cell bodies of large-caliber primary afferents that are usually located in the periphery in the dorsal root ganglia or trigeminal ganglia. The activity of these afferents is typically associated with proprioception of the jaw-closing muscles or mechanoreception on the teeth and periodontal ligament. However, like other large-caliber afferents from the body which display ectopic firing in neuropathic pain models, these afferents exhibit increased excitability and ectopic discharges even in a relatively mild muscle pain model. These discharges normally emerge from subthreshold membrane oscillations (SMOs) supported by a persistent sodium current (INaP) which is exquisitely sensitive to extracellular Ca2+-decreases. We have shown in the trigeminal main sensory nucleus that the release of a Ca2+-binding astrocytic protein, S100{beta}, is sufficient to modulate this sodium current. Here, we explore if this astrocyte-dependent mechanism contributes to emergence of this hyperexcitability and aim to localize the cellular site where ectopic discharge may arise using whole-cell patch-clamp recordings, confocal imaging, and immunohistochemistry methods on mice brain slices. We found that astrocytes, by lowering [Ca2+]e at focal points along the axons of NVmes neurons through S100{beta}, enhance the amplitude of the NaV1.6-dependent SMOs leading to ectopic firing. These findings suggest a crucial role for astrocytes in excitability regulation and raise questions about this neuron-astrocyte interaction as a key contributor to hyperexcitability in several pathologies.

neuroscience↗