Biology subjects

Fernandez, L. M.

Publications and source records attributed to Fernandez, L. M..

6 recordsLinked to original sources

bioRxiv2025

Vagal afferent activation induces a NREM-sleep-like state with brain-body cooling, but locus coeruleus activation

Parasympathetic nervous system activity, vital for restorative sleep, is influenced by vagal sensory afferents, but how these shape brain-body correlates of sleep remains open. We investigated this by combining vagal sensory neuron (VSN) stimulation with EEG/EMG, heart rate, brain-body temperature, and noradrenergic locus coeruleus (LC) neuron population activity measures. Opto-/chemogenetic VSN manipulations in Vglut2-Cre mice were validated via in vitro synaptic physiology, cFos expression, and heart rate measures. Chemogenetic VSN stimulation during the resting phase induced a non-rapid-eye-movement sleep (NREMS)-like state with enriched, but homeostatically regulated, low-frequency (0.75-4 Hz) EEG activity, yet suppressed REMS. Simultaneously, brain-body temperatures dropped while LC activity increased. Recovery was gradual towards normal NREMS-REMS-cycles but accelerated by external warming, identifying cooling as key factor. We conclude that VSN activation can promote brain-body correlates as a continuum of normal NREM sleep while engaging forebrain neuromodulation, offering insights into mechanisms of sleep disruptions linked to autonomic dysregulation.

neuroscience↗

bioRxiv2023

Locus coeruleus activity fluctuations set a non-reducible timeframe for mammalian NREM-REM sleep cycles

The noradrenergic locus coeruleus (LC) is vital for brain states underlying wakefulness, whereas its roles for sleep remain uncertain. Combining mouse sleep-wake monitoring, behavioral manipulations, LC fiber photometry and closed-loop optogenetics, we found that LC neuronal activity partitioned non-rapid-eye-movement sleep (NREMS) into alternating brain and autonomic states that rule the NREMS-REMS cycle. High LC activity levels generated an autonomic-subcortical arousal state that facilitated cortical microarousals, while low levels were obligatory for REMS entries. Timed optogenetic LC inhibition revealed that this functional alternation set the duration of the NREMS-REMS cycle by ruling REMS entries during undisturbed sleep and when pressure for REMS was high. A stimulus-enriched, stress-promoting wakefulness increased high LC activity levels at the expense of low ones in subsequent NREMS, fragmenting NREMS through microarousals and delaying REMS onset. We conclude that LC activity fluctuations gatekeep the NREM-REMS cycle over recurrent infraslow intervals, but they also convey vulnerability to adverse wake experiences.

neuroscience↗

bioRxiv2021

Infraslow locus coeruleus activity coordinates spindle rhythms and heart rate to gate fluctuating non-REM sleep substates

One promising approach towards understanding what makes sleep vulnerable in disease is to look at how wake-promoting mechanisms affect healthy sleep. Wake-promoting neuronal activity is inhibited during non-REM sleep (NREMS). However, many mammalian species, including humans, show recurrent moments of sleep fragility during which sensory reactivity is elevated. Wake-related neuronal activity could thus remain active in NREMS, but its roles in dynamic variations of sensory reactivity remain unknown. Here, we demonstrate that mouse NREMS is a brain state with recurrent fluctuations of the wake-promoting neurotransmitter noradrenaline on the [~]50-seconds time-scale. These fluctuations occurred around mean noradrenaline levels greater than the ones of quiet wakefulness, while they declined steeply in REMS. They coincided with a clustering of sleep spindle rhythms in the forebrain and with heart rate variations. We addressed the origins of these fluctuations by using closed-loop optogenetic locus coeruleus (LC) activation or inhibition timed to moments of low and high spindle activity during NREMS. We could suppress, lock or entrain sleep spindle clustering or heart rate variations, demonstrating that both fore- and hindbrain-projecting LC neurons show synchronized infraslow activity variations in natural NREMS. Noradrenergic modulation of thalamic but not cortical circuits was required for sleep spindle clustering and involved noradrenaline release into primary sensory and reticular thalamic nuclei that activated both 1- and {beta}-adrenergic receptors to cause slowly decaying membrane depolarizations. Noradrenergic signaling by LC, primarily known for attention promotion in wakefulness, renders mammalian NREMS more wake-like on the close-to-minute-time scale through sustaining thalamocortical and autonomic sensory arousability.

neuroscience↗

bioRxiv2021

Cortico-autonomic local arousals and heightened somatosensory arousability during NREM sleep of mice in neuropathic pain

Chronic pain patients frequently suffer from sleep disturbances. Improvement of sleep quality alleviates pain, but neurophysiological mechanisms underlying sleep disturbances require clarification to advance therapeutic strategies. Chronic pain causes high-frequency electrical activity in pain-processing cortical areas that could disrupt the normal process of low-frequency sleep rhythm generation. We found that the spared-nerve-injury (SNI) mouse model, mimicking human neuropathic pain, had preserved sleep-wake behavior. However, when we probed spontaneous arousability based on infraslow continuity-fragility dynamics of non-rapid-eye-movement sleep (NREMS), we found more numerous local cortical arousals accompanied by heart rate increases in hindlimb primary somatosensory, but not in prelimbic, cortices of SNI mice. Closed-loop mechanovibrational stimulation revealed higher sensory arousability in SNI. Sleep in chronic pain thus looked preserved in conventional measures but showed elevated spontaneous and evoked arousability. Our findings develop a novel moment-to-moment probing of NREMS fragility and propose that chronic pain-induced sleep complaints arise from perturbed arousability.

physiology↗

bioRxiv2020

Unicellular associative conditioning: an interspecies analysis

The capacity to learn new systemic behaviour is a fundamental issue to understand the adaptive mechanisms involved in cellular evolution. We have recently observed, in a preliminary analysis, the emergence of conditioned behaviour in individual amoebae cells. In these experiments, cells were able to acquire new migratory conduct and remember it for long periods of their cellular cycle, forgetting it later on. Here, following a similar conceptual framework of Pavlovs experiments, we have exhaustively studied the migration trajectories of more than 2000 individual cells belonging to three different species: Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis. Fundamentally, we have analysed several properties of conditioned cells, such as the intensity of the responses, the directionality persistence, the total distance traveled, the directionality ratio, the average speed, and the persistence times. We have observed that these three species can modify the systemic response to a specific stimulus by associative conditioning. Our main analysis shows that such new behaviour is very robust and presents a similar structure of migration patterns in the three species, which was characterized by the presence of conditioning for long periods, remarkable straightness in their trajectories and strong directional persistence. Our quantitative results, compared with other studies on complex cellular responses in bacteria, protozoa, fungus-like organisms and metazoans, allow us to conclude that cellular associative conditioning might be a widespread characteristic of unicellular organisms. This finding could be essential to understand some key evolutionary principles involved in increasing the cellular adaptive fitness to microenvironments.

systems biology↗

bioRxiv2019

Neural evidence of cognitive conflict during binocular rivalry

To make sense of ambiguous and, at times, incomplete sensory input, the brain relies on a process of active interpretation. At any given moment, only one of several possible perceptual outcomes prevails in our conscious experience. Our hypothesis is that the competition between alternative representations induces cognitive conflict, eventually leading to fluctuations between different perceptual interpretations. We used binocular rivalry, a popular protocol to probe changes in perceptual awareness [1-3] and drew on the conflict monitoring theory, which holds that cognitive control is invoked by the detection of conflict during information processing. We looked for an increase in power of fronto-medial theta oscillations (5-7 Hz), an established EEG marker of conflict detection [4-7]. Our results show that fm-theta power increases right before perceptual alternations and decreases thereafter, suggesting that conflict monitoring is related to perceptual competition. Furthermore, to investigate conflict resolution via attentional engagement, as held by the conflict monitoring theory [8], we also looked for changes in parieto-occipital alpha oscillations (8-12 Hz) associated to perceptual switches. These oscillations have been associated to attention allocation via functional inhibition in sensory cortices [9-12]. The power of parieto-occipital alpha was inversely related to that of fm-theta, reflecting periods of high inter-ocular inhibition during stable perception, and low inhibition around moments of perceptual change. Our findings validate a prediction made 20 years ago in the seminal paper formulating the conflict monitoring theory, and establish a previously unknown link between conflict mechanisms and the processes leading to perceptual awareness. HighlightsO_LIBinocular rivalry induces conflict between competing perceptual representations C_LIO_LIMid-frontal theta power increases around the resolution of perceptual conflict C_LIO_LIPosterior alpha decreases reflect neural excitability around perceptual switches C_LIO_LIThe results link cognitive conflict theory with perceptual inference C_LI

neuroscience↗