Biology subjects

Zubkov, M.

Publications and source records attributed to Zubkov, M..

8 recordsLinked to original sources

bioRxiv2025

The crosstalk between the anterior hypothalamus and the locus coeruleus during wakefulness is associated with low frequency oscillations power during sleep

Study ObjectivesAnimal research has demonstrated that sleep regulation heavily depends on a network of subcortical nuclei. In particular, whether the crosstalk between the Locus Coeruleus (LC) and hypothalamic nuclei influences sleep variability and age-related changes in humans remains unexplored. This study investigated whether the effective connectivity between the LC and subparts of the hypothalamus is associated with the electrophysiology of rapid eye movement sleep (REMS). MethodsThirty-three healthy younger ([~]22y, 27 women) and 18 older ([~]61y, 14 women) individuals underwent 7-Tesla functional magnetic resonance imaging during wakefulness to investigate the effective connectivity between LC and distinct hypothalamus subparts encompassing several nuclei. Additionally, we recorded their sleep electroencephalogram (EEG) to explore relationships between effective connectivity measures and REMS theta energy and sigma power prior to REMS episodes. ResultsThe effective connectivity analysis revealed robust evidence of a mutual positive influence between the LC and the anterior-superior and posterior hypothalamus, supporting the idea that the connectivity patterns observed in animal models are also present in humans. Furthermore, our results suggest that in older adults, stronger effective connectivity from the anterior-superior hypothalamus, including the preoptic area, to the LC is associated with reduced REM theta energy. Specificity analysis showed that this association was not limited to REM theta energy but also extended to specific lower-frequency bands during REMS and NREMS. ConclusionsThese findings highlight the complex age-dependent modulation of the LC circuitry and its role in sleep regulation. Understanding these neural interactions offers valuable insight into the mechanisms driving age-related sleep changes.

neuroscience↗

bioRxiv2025

Light Impact on Thalamo-Cortical Connectivity During an Executive Cognitive Task: Effects of Time of Day and Specificities of Teenagers

BackgroundLight affects not only vision but also attention, alertness, and cognition, primarily through intrinsically photosensitive retinal ganglion cells sensitive to blue-wavelength light. While previous research has shown that light influences brain regional activity, its impact on brain connectivity remains unclear. MethodsUsing 7-Tesla fMRI, this study examined how light illuminance modulates canonical left-lateralized verbal thalamo-prefrontal-parietal network connectivity during an auditory executive task. Fifty-five participants, including young adults (19-30 y, 23 Females: scanned in the morning or evening) and adolescents (15-18 y, 6 Females: scanned only in the evening), were studied. ResultsWe first found that across all the groups, moderate blue-enriched light strengthened parietal-to-frontal connectivity, while low-illuminance orange light enhanced thalamus-to-parietal connectivity. When focusing on time-of-day differences in young adults, we found that higher-illuminance blue-enriched light strengthened thalamus-to-prefrontal connectivity in the morning compared to the evening. When focusing on developmental stages differences, during the evening session only, we observe that moderate blue-enriched light enhanced thalamus-to-parietal connectivity in adolescents compared to young adults. ConclusionThese findings reinforce the view that the thalamus plays a key role in mediating the impact of light on cognition and the impact of light depends on the context of light administration, i.e. with timing and age.

neuroscience↗

bioRxiv2024

Cortical Excitability is Affected by Light Exposure- Distinct Effects in Adolescents and Young Adults

Light, particularly blue-wavelength light exerts a broad range of non-image forming (NIF) effects including the stimulation of cognition and alertness and the regulation of mood, sleep and circadian rhythms. However, its underlying brain mechanisms are not fully elucidated. Likewise, whether adolescents show a different NIF sensitivity to light compared to adults is not established. Here, we investigated whether cortical excitability, a basic aspect of brain function that depends on sleep-wake regulation, is affected by blue light and whether the effect is similar in young adults and adolescents. We used transcranial magnetic stimulation coupled to high-density electroencephalography (TMS-EEG) in healthy young adults (N=13, 24.2 {+/-} 3.4 y) and in adolescents (N=15, 16.9 {+/-} 1.1 y). Our results showed that, in young adults, blue light affected cortical excitability following an apparent inverted-U relationship, while adolescents cortical excitability was not significantly different under blue light compared to orange light. In addition, although light did not affect performance on a visuomotor vigilance task completed during the TMS-EEG recordings, cortical excitability was positively correlated to task performance in both age groups. This study provides valuable insights into the complex interplay between light, cortical excitability, and behavior. Our findings highlight the role of age in NIF effects of light, suggesting that brain responses to light differ during developmental periods.

neuroscience↗

bioRxiv2024

7 Tesla MRS estimates of GABA concentration relate to physiological measures of tonic inhibition in the human motor cortex

GABAergic neurotransmission within the cortex plays a key role in learning and is altered in several brain diseases. Quantification of bulk GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. A recent mathematical simulation contends that MRS detects extrasynaptic GABA, mediating tonic inhibition. Nevertheless, no empirical data have yet confirmed this hypothesis. Here we collected ultra-high field 7 Tesla MRS and Transcranial Magnetic Stimulation coupled with high-density Electroencephalography (TMS-hdEEG) from the motor cortex of twenty healthy participants (age 23.95{+/-}6.4), while they were at rest. We first applied a Neural Mass Model to TMS-evoked potentials to disentangle the contribution of different GABAergic pools. We then assessed to which of these different pools MRS-GABA was related to by means of Parametric Empirical Bayesian (PEB) analysis. We found that MRS-GABA was mostly positively related to the NMM-derived measures of tonic inhibition and overall functionality of the GABAergic synapse. This relationship was reliable enough to predict MRS-GABA from NMM-GABA. These findings clarify the mesoscopic underpinnings of GABA levels measured by MRS and will contribute to the concretization of MRS-GABA promises to improve our understanding of human behaviour, brain physiology and pathophysiology. Key pointsO_LIGABA neurotransmission is essential for synaptic plasticity and learning (especially motor learning) and is altered in several brain disorders, such as epilepsy and stroke. C_LIO_LIQuantification of GABA in the human brain is typically obtained by Magnetic Resonance Spectroscopy (MRS). However, the interpretation of MRS-GABA is still debated. C_LIO_LIBy using a biophysical Neural Mass Model, here we show that MRS-GABA relates to physiological measures of tonic inhibition in the human cortex. C_LI

neuroscience↗

bioRxiv2024

REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness

BackgroundAnimal studies established that the locus coeruleus (LC) plays important roles in sleep and wakefulness regulation. Whether it contributes to sleep variability in humans is not yet established. Here, we investigated if the in vivo activity of the LC is related to the variability in the quality of Rapid Eye Movement (REM) sleep. MethodsWe assessed the LC activity of 34 healthy younger ([~]22y) and 18 older ([~]61y) individuals engaged in bottom-up and top-down cognitive tasks using 7-Tesla functional Magnetic Resonance Imaging (fMRI). We further recorded their sleep electroencephalogram (EEG) to evaluate associations between LC fMRI measures and REM sleep EEG metrics. ResultsTheta oscillation energy during REM sleep was positively associated with LC response in the top-down task. In contrast, REM sleep theta energy was negatively associated with LC activity in older individuals during the bottom-up task. Importantly, sigma oscillations power immediately preceding a REM sleep episode was positively associated with LC activity in the top-down task. ConclusionsLC activity during wakefulness was related to REM sleep intensity and to a transient EEG change preceding REM sleep, a feature causally related to LC activity in animal studies. The associations depend on the cognitive task, suggesting that a balanced level of LC tonic activity during wakefulness is required for optimal expression of REM sleep. The findings may have implications for the high prevalence of sleep complaints reported in aging and for disorders such as insomnia, Alzheimers, and Parkinsons disease, for which the LC may play pivotal roles through sleep.

neuroscience↗

bioRxiv2024

Exposure to light supresses the activity of the medial and superior amygdala during emotional processing

The brain mechanisms through which changes in season and light exposure modulate mood may involve different nuclei of the amygdala. We aimed to test this hypothesis using 7 Tesla functional magnetic resonance imaging in 29 healthy young adults. We first considered time-of-year changes in activity that are related to the slow change in photoperiod. We find that the response to emotional stimuli of selected medial and superior nuclei of the amygdala peaked around the start of winter or increased with worse mood status. We further assessed how alternating short exposures to light of different illuminance acutely affected the regional activity of the amygdala. We show that the same areas showed a linear reduction of activity when exposed to increasing light illuminance, specifically when processing emotional stimuli. Importantly, the impact of light on part of these nuclei peaked around the start of summer or decreased with worse mood. These findings provide new evidence that humans show seasonality and that, for mood, it involves parts of the amygdala. The results bring novel insights into the mechanisms that underlie the long-term and acute impact of light on mood and that may contribute to the benefits of light therapy in the treatment of mood disorders.

neuroscience↗

bioRxiv2023

Regional response to light illuminance across the human hypothalamus

Light exerts multiple non-image-forming biological effects on physiology including the stimulation of alertness and cognition. However, the subcortical circuitry underlying the stimulating impact of light is not established in humans. We used 7 Tesla functional magnetic resonance imaging to assess the impact of variations in light illuminance on the regional activity of the hypothalamus while healthy young adults (N=26; 16 women; 24.3 {+/-} 2.9y) were completing two auditory cognitive tasks. We find that, during both the executive and emotional tasks, higher illuminance triggered an activity increase over the posterior part of the hypothalamus, which includes part of the tuberomamillary nucleus and the posterior part of the lateral hypothalamus. In contrast, increasing illuminance evoked a decrease in activity over the anterior and ventral parts of the hypothalamus, encompassing notably the suprachiasmatic nucleus and another part of the tuberomammillary nucleus. Critically, the performance of the executive task was improved under higher illuminance and was negatively correlated with the activity of the posterior hypothalamus area. These findings reveal the distinct local dynamics of different hypothalamus regions that underlie the impact of light on cognition.

neuroscience↗

bioRxiv2023

A redox switch allows binding of ferrous and ferric ions in the cyanobacterial iron binding protein FutA from Prochlorococcus

The marine cyanobacterium Prochlorococcus is a main contributor to global photosynthesis, whilst being limited by iron availability. Cyanobacterial genomes typically encode two different types of FutA iron binding proteins: periplasmic FutA2 ABC transporter subunits bind Fe(III), while cytosolic FutA1 binds Fe(II). Owing to their small size and their economized genome Prochlorococcus ecotypes typically possess a single futA gene. How the encoded FutA protein might bind different Fe oxidation states was previously unknown. Here we use structural biology techniques at room temperature to probe the dynamic behavior of FutA. Neutron diffraction confirmed four negatively charged tyrosinates, that together with a neutral water molecule coordinate iron in trigonal bipyramidal geometry. Positioning of the positively charged Arg103 side chain in the second coordination shell yields an overall charge-neutral Fe(III) binding state in structures determined by neutron diffraction and serial femtosecond crystallography. Conventional rotation X-ray crystallography using a home source revealed X-ray induced photoreduction of the iron center with observation of the Fe(II) binding state; here, an additional positioning of the Arg203 side chain in the second coordination shell maintained an overall charge neutral Fe(II) binding site. Dose series using serial synchrotron crystallography and an XFEL X-ray pump-probe approach capture the transition between Fe(III) and Fe(II) states, revealing how Arg203 operates as a switch to accommodate the different iron oxidation states. This switching ability of the Prochlorococcus FutA protein may reflect ecological adaptation by genome streamlining and loss of specialized FutA proteins. Significance StatementOceanic primary production by marine cyanobacteria is a main contributor to carbon and nitrogen fixation. Prochlorococcus is the most abundant photosynthetic organism on Earth, with an annual carbon fixation comparable to the net global primary production from agriculture. Its remarkable ecological success is based on the ability to thrive in low nutrient waters. To manage iron limitation, Prochlorococcus possesses the FutA protein for iron uptake and homeostasis. We reveal a molecular switch in the FutA protein that allows it to accommodate binding of iron in either the Fe(III) or Fe(II) state using structural biology techniques at room temperature and provide a plausible mechanism for iron binding promiscuity.

biophysics↗