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Belle, M. D.

Publications and source records attributed to Belle, M. D..

2 recordsLinked to original sources

Conserved circadian membrane rhythms arise from divergent cellular mechanisms in pacemaker neurons of mice and Drosophila

Circadian clocks align physiology and behaviour with daily environmental cycles, requiring neuronal networks that reliably encode and transmit time-of-day information. A fundamental yet unresolved question is how membrane properties support this function and whether conserved principles arise across evolutionarily distant organisms. We compared the intrinsic electrophysiological properties of identified circadian neurons from a nocturnal mammal (mouse, Mus musculus SCN VIP neurons) and a diurnal insect (fly, Drosophila melanogaster l-LNv PDF neurons) across the 24-h light-dark cycle. Despite [~]700 million years of evolutionary divergence and opposite temporal niches, we found neurons from both species exhibited similar rhythmic patterns in key parameters for encoding time-of-day, including resting membrane potential, spontaneous firing rate and cell capacitance, indicating convergent strategies for generating daily variation in excitability despite dramatically different network scales ([~]2200 VIPs vs. 8 l-LNvs). These shared outputs arose through distinct mechanisms: flies exhibited higher input resistance, greater excitability and relatively larger A-type potassium currents, while mice displayed larger sustained outward currents and post-inhibitory rebound excitation, absent in flies. Rheobase troughs occurred during the inactive phase in both species, while other parameters did not cycle. These differences likely shape how each neuronal type integrates salient inputs, consistent with their respective roles in processing sustained daytime light (flies) versus nocturnal cues (mice). Our findings reveal conserved functional goals but divergent electrophysiological strategies in circadian neurons, reflecting evolutionary adaptation to species-specific environmental demands. Such neurophysiological diversity highlights how evolution shapes cellular mechanisms to meet the requirements of temporal niche while preserving robust circadian timekeeping.

neuroscience↗

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↗