Biology subjects

Milosavljevic, N.

Publications and source records attributed to Milosavljevic, N..

5 recordsLinked to original sources

bioRxiv2026

Parallel visual processing in the suprachiasmatic region of a diurnal mammal.

Light shapes mammalian physiology and behaviour through hypothalamic pathways, yet how these pathways process visual information in day-active species remains poorly understood. Based largely on work in nocturnal rodents, the suprachiasmatic nucleus (SCN) is classically viewed as a retinal target that encodes ambient illumination for circadian entrainment. We combine anatomical tracing, light-evoked c-Fos mapping and high-density silicon-probe electrophysiology to define visual processing in the suprachiasmatic region of the diurnal murid Rhabdomys pumilio. We find that retinal input and light-evoked activity extend beyond the SCN into rostral and lateral peri-SCN hypothalamus. Within the SCN, neurons encode irradiance with graded changes in maintained firing broadly similar to those observed in parallel recordings of nocturnal Mus domesticus. Across the wider suprachiasmatic region, Rhabdomys neurons show selectivity for more dynamic visual stimuli, including luminance transitions, contrast and temporal structure. Unsupervised clustering identifies five functionally distinct hypothalamic visual response classes with different anatomical distributions. These findings reveal an expanded hypothalamic visual network in a diurnal mammal, placing SCN irradiance coding within a broader system for processing dynamic visual features.

neuroscience↗

bioRxiv2026

Acute and cumulative light exposure differentially influence mood in healthy adults

Light influences mood in both clinical and experimental settings, yet it remains unclear how ambient light exposure relates to mood in daily life, which dimensions of mood are most sensitive to light and over what timescales these associations emerge. Here, we combined continuous personal light monitoring using wearable light sensors with repeated assessments of multiple dimensions of mood and affect, including self-reported mood ratings and cognitive measures of affective bias, alongside physiological monitoring in 49 healthy adults living under naturalistic conditions. Brighter light was consistently associated with more positive self-reported mood. Associations emerged over distinct temporal windows, with greater melanopic irradiance during the preceding 30 min associated with increased feelings of energy. Importantly, this association remained significant after accounting for alertness, physical activity and sleep-related covariates, suggesting that it is not solely explained by the established alerting effects of light. In contrast, several positive mood dimensions, including happiness, feeling accompanied, enjoyment, motivation and relaxation, were associated with light accumulated over longer periods (60-240 min). Furthermore, happiness, feeling accompanied, enjoyment and relaxation, but not energy, were also associated with greater cumulative daily exposure to light above 250 lux melanopic equivalent daylight illuminance (EDI), a threshold proposed to support healthy daytime light exposure. Behavioural measures of affective bias showed no robust associations with light exposure. Together, these findings indicate that everyday light exposure is associated with distinct dimensions of mood over different timescales, highlighting a complex relationship between light and affect in daily life. Significance StatementLight is a promising target for improving mental health, yet little is known about how everyday light exposure relates to mood outside laboratory and clinical settings. Using wearable light sensors and repeated mood assessments in healthy adults living under naturalistic conditions, we show that different dimensions of mood are linked to light exposure over distinct timescales, from recent exposure to cumulative light history. Importantly, the association between recent light exposure and feelings of energy remained independent of physical activity and sleep-related factors. These findings demonstrate that effects of light on mood are dynamic and multidimensional, highlighting the need to move beyond simple measures of total light exposure and informing future efforts to design healthier light environments that support emotional wellbeing.

neuroscience↗

bioRxiv2024

Reconfiguration of the visual code and retinal cell type complement in closely related diurnal and nocturnal mice

How does evolution act on neuronal populations to match computational characteristics to functional demands? We address this problem by comparing visual code and retinal cell composition in closely related murid species with different behaviours. Rhabdomys pumilio are diurnal and have substantially thicker inner retina and larger visual thalamus than nocturnal Mus musculus. High-density electrophysiological recordings of visual response features in the dorsal lateral geniculate nucleus (dLGN) reveals that Rhabdomys attains higher spatiotemporal acuity both by denser coverage of the visual scene and a selective expansion of elements of the code characterised by non-linear spatiotemporal summation. Comparative analysis of single cell transcriptomic cell atlases reveals that realignment of the visual code is associated with increased relative abundance of bipolar and ganglion cell types supporting OFF and ON-OFF responses. These findings demonstrate how changes in retinal cell complement can reconfigure the coding of visual information to match changes in visual needs.

neuroscience↗

bioRxiv2021

A Bioinformatic and Empiric Exploration of Prokaryotic Argonautes as Novel Programmable Endonuclease Systems

Argonautes are nucleases that can be programmed by short oligonucleotides to cleave complementary sequences. Here, we performed an unbiased bioinformatic search to mine bacterial genomes for prokaryotic Argonautes (pAgos) harboring a PIWI domain. Our search identified 3,033 pAgos in total, of which 1,464 portend to the subgroup of long pAgos with more than 600 amino acids. We purified a subset of 49 pAgos which were found in proximity to helicases and tested their nuclease activity in vitro. Ten of these were active towards single-stranded DNA substrates and this activity could be programmed by exogenous guide DNAs or RNAs. Cleavage of double-stranded plasmid DNA was much less readily observed and was fostered by elevated temperatures or exogenous addition of a DNA single-strand binding protein (ET-SSB). The efficiency of pAgo-mediated plasmid cleavage was dependent on the DNA target sequence as well as the surrounding sequence, suggesting that unwinding of the DNA double helix was a limiting factor. Intriguingly, we identified a cluster of pAgos from the Clostridial clade which was active at 37{degrees}C and activity was enhanced by exogenous ET-SSB. This suggests that Clostridial pAgos may be particularly suited to catalyze DNA double-strand cleavage and implies that such pAgos may be repurposed as gene editing tools in future.

molecular biology↗

bioRxiv2020

Using a bistable animal opsin for switchable and scalable optogenetic inhibition of neurons

There is no consensus on the best optogenetic tool for neuronal inhibition. Lamprey parapinopsin ( Lamplight) is a Gi/o-coupled bistable animal opsin that can be activated and deactivated by short and long wavelength light, respectively. Since native mechanisms of neuronal inhibition frequently employ Gi/o signalling, we asked here whether Lamplight could be used for optogenetic silencing. We show that short (405nm) and long (525nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, and that combining these wavelengths can be used to achieve intermediate levels of activity. We demonstrate that these properties can be applied to produce switchable and scalable neuronal hyperpolarisation, and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. We show that expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, and that 405 and 525nm stimuli can produce responses of opposite sign in output neurons of the retina. Lamplight-driven responses to both activating (405nm) and deactivating (525nm) light can occur within 500ms and be elicited by intensities at least 10x below threshold for available inhibitory optogenetic tools. We conclude that Lamplight can co-opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and rapidly reversible.

neuroscience↗