Biology subjects

Gronfier, C.

Publications and source records attributed to Gronfier, C..

5 recordsLinked to original sources

bioRxiv2025

Within-subject rhythmicity and stability of hunger, satiety, and physiological markers: insights from a five-day laboratory study in time-isolation conditions

Hunger and satiety are interoceptions involved in the control of food intake. How they change across the day and from one day to the next, as well as their relationships with physiological parameters, remain poorly understood. In a five-day laboratory study, twenty healthy male participants (24.2 {+/-} 3.3 years) were given three meals per day (breakfast, lunch, dinner), at times based on each individuals internal time. Subjects had an 8-h sleep opportunity at night recorded by polysomnography, during which time they were exposed to 4 different light intensities (0, 3, 8, or 20 lux). Hunger and satiety were assessed before and after each meal. Heart rate was measured continuously and glucose levels were sampled every 15 minutes. We found that: 1) Hunger and satiety varied dynamically with the lowest levels at breakfast and the highest at lunch and dinner (p < 0.01); 2) the intensity of hunger and satiety remained stable across the five experimental days, and were subject-dependent; 3) Heart rate was higher after than before meals (p < 0.0001), and higher around breakfast than dinner; 4) Glycemia before and after meals was respectively stable throughout the day and over the study period; 5) Interoception was correlated with fluctuations in heart rate, glucose levels and sleep duration. Overall, our results reveal that hunger and satiety perception are individual characteristics. To better understand the role of interoception in food intake control, both hunger and satiety should be measured, but separately in their respective states.

physiology↗

bioRxiv2025

The acute sleep-inducing effects of light require histamine neurotransmission in mice

Sleep regulation depends on the complex interplay between homeostatic and circadian processes synchronized by the light/dark cycle. Sleep is also directly regulated by light via the retinal inputs to the preoptic area (POA). Although the light-responsive POA neurons project to several wake-promoting structures, including histaminergic neurons in the tuberomammillary nucleus (TMn), there is no functional evidence for their involvement in light-induced sleep. To bridge this gap, we used histidine decarboxylase (HDC, the histamine-synthetizing enzyme) knockout mice (HDC-/-, n=7) and hM4Di-HDC-cre mice (HDC+/+, n=8) subjected to an ultradian light/dark protocol (LD 1h:1h over 24h), and another group of hM4Di-HDC-cre mice (n=8) exposed to a 1-h light pulse. We found that light pulses during the biological night enhanced slow wave sleep and increased cortical EEG power in the delta range (0.5-3Hz), and that these effects were significantly attenuated both in HDC-/- (83 vs 23 min/6h, p=0.005) under LD 1h:1h condition and in hM4Di-HDC-cre mice after acute chemogenetic silencing of histamine neurons by the DREADD ligand deschloroclozapine (15 vs 6 min/h, p=0.0016) under a 1-h light pulse. In addition, the sleep-inducing effect of light was circadian dependent, with the strongest effect at the beginning and end of the night but no effect at all during the biological day in HDC+/+mice. Our study provides functional evidence that the acute sleep-inducing effects of light on sleep require histamine neurotransmission in mice.

neuroscience↗

bioRxiv2024

Circadian rhythmicity and photobiological mechanisms of light sensitivity and discomfort glare in humans

Discomfort glare is a common visual sensation, which is generally reported when being exposed to a brighter lit environment. In certain clinical conditions, this sensation is abnormally amplified, and is commonly named photophobia. Despite the frequent appearance of this sensation in everyday life or in pathological conditions, the underlying mechanisms remain poorly understood. We show here, in highly controlled laboratory constant routine conditions, that light-induced discomfort glare is rhythmic over the 24-hour day. We reveal a strong circadian drive, with a sinusoidal rhythmicity, with maximal discomfort glare in the middle of the night and minimal in the afternoon. We also find a modest sleep-related homeostatic drive of visual discomfort, with a linear increase in discomfort glare over 34 hours of prolonged wakefulness. Our study reveals that discomfort glare is primarily driven by the ipRGC pathway, and that mid and/or long wavelengths cones are involved as well. The 6.5-hour phase lag between the rhythms of photoreceptors sensitivity, assessed through pupillary light reflex, and of glare discomfort, suggests two independent underlying mechanisms. In conclusion, our findings highlight the need to take time-of-day and biological rhythmicity into account in the evaluation of light-induced discomfort glare. Apprehending these mechanisms may help understand photophobia in clinical populations, such as in migraine patients, and should be taken into account to optimize light quality at home and at the workplace, both for day and night work.

neuroscience↗

bioRxiv2023

Melatonin suppression by light involves different retinal photoreceptors in young and older adults

IntroductionAge-related sleep and circadian rhythm disturbances may be due to altered non-visual photoreception. Here, we investigated the temporal dynamics of light-induced melatonin suppression in young and older individuals. MethodsIn a within-subject design study, young and older participants were exposed for 60 minutes (0030-0130 at night) to 9 narrow-band lights (range: 420 to 620 nm). Plasma melatonin suppression was calculated at 15, 30, 45, and 60 min time intervals. Individual spectral sensitivity of melatonin suppression and photoreceptor contribution were predicted for each interval and age group. ResultsIn young participants, melanopsin solely drove melatonin suppression at all time intervals, with an invariant peak sensitivity at [~]485 nm established only after 15 minutes of light exposure. Conversely, in older participants, spectral light-driven melatonin suppression was best explained by a model combining melanopsin + L-cones with a stable peak sensitivity ([~]499 nm) at 30, 45, and 60 minutes of light exposure. ConclusionAging is associated with a distinct photoreceptor contribution to melatonin suppression by light. While in young adults melanopsin-only photoreception is a reliable predictor of melatonin suppression, in older individuals this process is jointly driven by melanopsin and L-cones. These findings offer new prospects for customizing light therapy for older individuals.

neuroscience↗

bioRxiv2020

Evidence that pain sensitivity is rhythmic in humans, mainly driven by the endogenous circadian system and little by sleep

Pain intensity has been reported to fluctuate during the day in some experimental and clinical conditions, but the mechanisms underlying these fluctuations are unknown. Although the circadian timing system is known to regulate a wide range of physiological functions, its implication in pain regulation is unknown. We show here, using highly controlled laboratory constant routine conditions, that pain sensitivity is rhythmic over the 24-hours and strongly controlled by the endogenous circadian timing system. We find that pain sensitivity follows a sinusoidal circadian rhythmicity, with a maximum in the middle of the night and a minimum in the afternoon. We also find a weak homeostatic control of pain sensitivity, with a linear increase over the 34 hours of prolonged wakefulness, which parallels that of sleep pressure. Using mathematical modelling, we describe that the circadian system accounts for 80% of the full magnitude of pain sensitivity over the 24 hours, and that sleep-related processes account for only 20%. This result reveals that nocturnal analgesia is predominantly induced by the circadian system and has been wrongly attributed only to sleep. Our findings highlight the need to consider the time of day in pain assessment, and suggest that personalized circadian medicine may be a promising approach to pain management. Significance statementWe discovered that sensitivity to pain is rhythmic in healthy humans, that sensitivity is maximal at night and minimal in the afternoon. Contrarily to the current thinking that sleep is the best painkiller, we find that the 24-h rhythmicity of sensitivity to pain is mainly controlled by a biological circadian clock in our body, and very little by our sleep. Our article reveals the neurobiological mechanisms involved in driving the rhythmicity of pain perception in humans, with the main time-piece located in the brain (the suprachiasmatic nuclei in the hypothalamus). Our findings challenge the current vision of pain physiology, and reveal the need to consider time-of-day and internal biological time for pain evaluation and pain management.

neuroscience↗