Biology subjects

Bandarabadi, M.

Publications and source records attributed to Bandarabadi, M..

6 recordsLinked to original sources

bioRxiv2024

Brain resident macrophages regulate sleep, with repopulated ones being unable to reestablish the original sleep circuits

Sleep is a complex behavior regulated by various brain cell types. However, the roles of brain-resident macrophages, including microglia and CNS-associated macrophages (CAMs), particularly those derived postnatally, in sleep regulation remain poorly understood. Here, we investigated the effects of natural (embryo-derived) and repopulated (postnatally derived) brain-resident macrophages on the regulation of vigilance states. We found that depletion in embryonically-derived brain macrophages caused increased sleep in the active period, but reduced its quality, reflected in reduced power of brain sleep oscillations. This was observed both for the Non-REM and REM sleep stages. Subsequent repopulation by postnatal brain macrophages unexpectedly failed to reestablish normal sleep-wake patterns and additionally induced sleep fragmentation. Furthermore, brain macrophage depletion caused excitatory-inhibitory synaptic imbalance, which was resistant to repopulation, and led to increased inhibitory synapses. At the metabolite level, the distinct metabolite profile induced by brain macrophage depletion largely returned to normal after repopulation. Our findings suggest a so far largely unknown interaction between brain-resident macrophages and sleep and emphasizes striking functional differences between embryonic and postnatally-derived brain macrophages, paving the way to future exploration of the role of brain macrophages of different origin in sleep disorders and synaptic connectivity.

neuroscience↗

bioRxiv2023

Hypothalamic control of noradrenergic neurons stabilizes sleep

Hypocretin/orexin neurons are essential to stabilize sleep, but the underlying mechanisms remain elusive. We report that hypocretin neurons of the perifornical hypothalamus are highly active during rapid eye movement sleep and show state-specific correlation with noradrenergic neurons. Deletion of hypocretin gene significantly increased periodic reactivations of locus coeruleus noradrenergic neurons during sleep and dysregulated their activity across transitions, suggesting a role for hypocretin neurons in mediating neuromodulation to stabilize sleep.

neuroscience↗

bioRxiv2022

Orexin action on the dopaminergic system modulates theta during REM sleep and wakefulness

Both dopaminergic (DA) and orexinergic (OX) systems establish brain-wide neuromodulatory circuits that profoundly influence brain states and behavioral outputs. To unravel their interactions, we inactivated OX-to-DA neurotransmission by selective disruption of HcrtR1/OxR1, or HcrtR2/OxR2, or both receptors, in DA neurons. Chronic loss of OXR2 in DA neurons (OxR2Dat-CKO mice) dramatically increased electrocorticographic (EcoG) theta rhythms in wakefulness and REM sleep. Episode duration and total times spent in active wakefulness and REMS were prolonged, and theta/fast-gamma wave coupling was enhanced in both states. Increased theta in OxR2DatCKO mice baseline wake was accompanied by diminished infra-theta and increased fast-gamma activities, i.e. the mice exhibited signs of constitutive electrocortical hyperarousal, albeit uncoupled with locomotor activity. These effects were not seen in OxR1-ablated dopaminergic mutants, which tended to show opposite phenotypes, resembling those caused by the loss of both receptors. Our data establish a clear, genetically-defined link between monosynaptic orexin-to-dopaminergic connectivity and the power of theta oscillations, with a differential role of OXR2 in cross-frequency wave coupling and attentional processes.

neuroscience↗

bioRxiv2021

Deficient thalamo-cortical networks dynamics and sleep homeostatic processes in a redox dysregulation model relevant to schizophrenia.

A growing body of evidence implicates thalamo-cortical oscillations with the neuropathophysiology of schizophrenia (SZ) in both mice and humans. Yet, the precise mechanisms underlying sleep perturbations in SZ remain unclear. Here, we characterised the dynamics of thalamo-cortical networks across sleep-wake states in a mouse model carrying a mutation in the enzyme glutathione synthetase gene (Gclm-/-) associated with SZ in humans. We hypothesised that deficits in parvalbumin immunoreactive cells in the thalamic reticular nucleus (TRN) and the anterior cingulate cortex (ACC) - caused by oxidative stress - impact thalamocortical dynamics, thus affecting non-rapid eye movement (NREM) sleep and sleep homeostasis. Using polysomnographic recordings in mice, we showed that KO mice exhibited a fragmented sleep architecture, similar to SZ patients and altered sleep homeostasis responses revealed by an increase in NREM latency and slow wave activities during the recovery period (SR). Although NREM sleep spindle rate during spontaneous sleep was similar in Gclm-/- and Gcml +/+, KO mice lacked a proper homeostatic response during SR. Interestingly, using multisite electrophysiological recordings in freely-moving mice, we found that high order thalamic network dynamics showed increased synchronisation, that was exacerbated during the sleep recovery period subsequent to SD, possibly due to lower bursting activity in TRN-antero dorsal thalamus circuit in KO compared to WT littermates. Collectively, these findings provide a mechanism for SZ associated deficits of thalamo-cortical neuron dynamics and perturbations of sleep architecture.

neuroscience↗

bioRxiv2019

The paternally imprinted gene Snord116 regulates cortical neuronal activity

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by rapid eye movement (REM) sleep abnormalities. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in both humans and mice.\n\nHere, we further explore the processes of sleep regulation by studying the PWScrm+/p- mouse line, which carries a paternal deletion of Snord116. We focused on microstructural electrophysiological components of sleep, such as REM sleep features and sleep spindles within NREM sleep. While the former are thought to contribute to neuronal network formation early in brain development, the latter are markers of thalamocortical processes. Both signals are often compromised in neurodevelopmental disorders and influence functional properties of cortical neurons. Thus, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array (MEA) studies.\n\nOur results indicate that the Snord116 gene in mice selectively influences REM sleep properties, such as theta rhythms and the organization of REM episodes throughout sleep-wake cycles. Moreover, sleep spindles present specific abnormalities in PWS model systems, indicating that these features of sleep may translate as potential biomarkers in human PWS. We observed abnormalities in the synchronization of cortical neuronal activity that are accounted for by high levels of norepinephrine.\n\nIn conclusion, our results provide support for an important role of Snord116 in regulating brain activity during sleep and, in particular, cortical neuronal properties, thereby opening new avenues for developing interventions in PWS.\n\nSignificance StatementWe found that the Snord116 gene, a major player in Prader-Willi syndrome (PWS), significantly impacts REM sleep and its regulation. Additionally, we found that sleep spindles, a subtle electroencephalography (EEG) marker that occurs during NREM sleep, are dysregulated in PWS mice that carry a paternal deletion of the Snord116 gene. Using a combination of in vivo and in vitro experiments, we identified sleep features at the network and molecular level that suggest that Snord116 is fundamental in the synchronization of neuronal networks. Our study also provides a new pre-clinical tool to investigate the pathophysiology of sleep in PWS.

neuroscience↗

bioRxiv2017

Dynamical modulation of theta-gamma coupling during REM sleep

Theta phase modulates gamma amplitude during spatial navigation and rapid eye movement sleep (REMs). Although the REMs theta rhythm has been linked to spatial memory consolidation, the underlying mechanism remains unclear. We investigate dynamics of theta-gamma interactions across multiple frequency and temporal scales in simultaneous recordings from hippocampal CA3, CA1, subiculum, and parietal cortex. We show that theta phase significantly modulates three distinct gamma bands during REMs, dynamically. Interestingly, we further show that theta-gamma coupling swings between different hippocampal and cortical structures during REMs and tends to increase over a single REMs episode. Comparing to active wake, theta-gamma coupling during REMs is significantly increased for subicular and cortical, but not for CA3 and CA1, recordings. Finally, optogenetic silencing of septohippocampal GABAergic projections significantly impedes both theta-gamma coupling and theta phase coherence, two neural mechanisms of working and long-term memory, respectively. Thus, we show that theta-gamma coupling and theta phase coherence are highly modulated during single REMs episode and propose that theta-gamma coupling provides a predominant mechanism for information processing within each brain region, while the orchestrated nature of coupling activity establishes a specific phase-space coding of information during sleep.

neuroscience↗