Biology subjects

de Lecea, L.

Publications and source records attributed to de Lecea, L..

4 recordsLinked to original sources

bioRxiv2021

Correlates of Sleep and Arousal via Matrix Methods

Conventional computational modeling of sleep and arousal are primarily brain-centric in restricting attention to data from the nervous system. While such a view is warranted, the importance of considering the coupling of peripheral systems in the causes and effects of sleep are being increasingly recognized. An analysis is presented that has the capability to incorporate neural recordings of different modalities as well as data from the metabolic and immune systems. We formulate a matrix-based approach for inference of the arousal state based on the activity level of cell types that will comprise the matrix components. While the presented computations are intended to predict sleep/arousal, it is anticipated that a scrutiny of the structure of the matrices will provide insight into the dynamics of the constituent systems. A model is also proposed to consider the interaction of the signals recorded across the neural, metabolic, and immune systems in leading to the arousal state.

neuroscience↗

bioRxiv2020

Adolescent sleep is critical for the developmental shaping of social novelty preference

Sleep takes one-third of our lives, yet its functions remain largely unknown. A large proportion of young patients with neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia have sleep problems, including delayed sleep onset, shortened sleep duration and sleep fragmentation, which have been linked to social interaction deficit, a shared symptom of these disorders. However, the causal relationship between sleep disruption and social defects as well as the underlying mechanisms have not yet been established despite its importance in understanding the etiology of these disorders and developing potential therapeutic means. Here using the three-chamber social interaction test, we found that developmental sleep disruption (SD) in adolescent mice caused significant and long-lasting impairment in the preference towards social novelty during adult social interactions without affecting the overall sociality. Interestingly, SD performed in the adulthood did not induce any social defect, indicating a critical period within adolescence during which sleep shapes social novelty preference. Furthermore, by analyzing the adolescent sleep and adult social behavior in a mouse model of Shank3 mutation that mimics a genetic aberrance in ASDs, we found that the development of sociality is correlated with adolescent NREM sleep while social novelty preference is correlated with adolescent REM sleep. Collectively, these results demonstrate a critical role of adolescent sleep in the forming of social novelty preference and the developmental shaping of social behavior.

neuroscience↗

bioRxiv2020

Hypothalamic circuitry underlying stress-induced insomnia and peripheral immunosuppression

The neural substrates of insomnia/hyperarousal induced by stress remain unknown. Here, we show that restraint stress leads to hyperarousal associated with strong activation of corticotropin-releasing hormone neurons in the paraventricular nucleus of hypothalamus (CRHPVN) and hypocretin neurons in the lateral hypothalamus (HcrtLH). CRHPVN neurons are quiescent during natural sleep-wake transitions but are strongly active under restraint stress. CRISPR-Cas9-mediated knockdown of the crh gene in CRHPVN neurons abolishes hyperarousal elicited by stimulating LH-projecting CRHPVN neurons. Genetic ablation of Hcrt neurons or crh gene knockdown significantly reduces insomnia/hyperarousal induced by restraint stress. Given the association between stress and immune function, we used single-cell mass cytometry by time of flight (CyTOF) to analyze peripheral blood and found extensive changes to immune cell distribution and functional responses during wakefulness upon optogenetic stimulation of CRHPVN neurons. Our findings suggest both central and peripheral systems are synergistically engaged in the response to stress via CRHPVN circuitry.

neuroscience↗

bioRxiv2019

Arousal-State Dependent Alterations in VTA-GABAergic Neural Activity

Decades of research have implicated the ventral tegmental area (VTA) in motivation, reinforcement learning and reward processing. We and others recently demonstrated that it also serves as an important node in sleep/wake circuitry. Specifically, VTA-dopaminergic neuron activation is sufficient to drive wakefulness and necessary for the maintenance of wakefulness. However, the role of VTA gamma-aminobutyric acid (GABA)-expressing neurons in arousal regulation is not fully understood. It is still unclear whether VTA-GABAergic neurons predictably alter their firing properties across arousal states, what is the nature of interactions between VTA-GABAergic activity and cortical neural oscillations, and how activity in VTA-GABAergic neurons relates to VTA-dopaminergic neurons in the context of sleep/wake regulation. To address these questions, we simultaneously recorded population activity from VTA-GABAergic or VTA-dopaminergic neurons and EEG/EMG signals during spontaneous sleep/wake states and in the presence of salient stimuli in freely-behaving male mice. We observed that VTA-GABAergic neurons exhibit robust arousal-state-dependent alterations in population activity, with high activity and calcium transients during wakefulness and rapid-eye-movement (REM) sleep compared to non-REM (NREM) sleep. During wakefulness, population activity of VTA-GABAergic neurons, but not VTA-dopaminergic neurons, was positively correlated with EEG gamma power and negatively correlated with EEG theta power. During NREM sleep, population activity in both VTA-GABAergic and VTA-dopaminergic neurons negatively correlated with delta, theta, and sigma EEG power bands. Salient stimuli, with both positive and negative valence, activated VTA-GABAergic neurons. The strongest activation was observed for social stimuli irrespective of valence. Together, our data indicate that VTA-GABAergic neurons, like their dopaminergic counterparts, drastically alter their activity across sleep-wake states. Changes in their activity predicts cortical oscillatory patterns reflected in the EEG, which are distinct from EEG spectra associated with dopaminergic neural activity.\n\nStatement of SignificanceLittle is known about how ventral tegmental area (VTA) neural ensembles couple arousal to motivated behaviors. Using cell-type specific genetic tools, we investigated the population activity of GABAergic and dopaminergic neurons within the VTA across sleep/wake states and in the presence of salient stimuli. We demonstrate that coordinated neural activity within VTA-GABAergic neurons peaks during wakefulness and REM sleep. Furthermore, neuronal activity in VTA-GABAergic neurons is correlated with high frequency, low amplitude cortical oscillations during waking, but negatively correlated with high amplitude slower frequency oscillations during NREM sleep. Our results demonstrate that VTA-GABAergic neuronal activity is tightly linked to cortical arousal and highlight this population as a potential important node in sleep/wake regulation.

neuroscience↗