The Functional Connectome Mediating Circadian Synchrony in the Suprachiasmatic Nucleus DOI Creative Commons
K. L. Nikhil, Bharat Singhal, Daniel Granados‐Fuentes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract Circadian rhythms in mammals arise from the spatiotemporal synchronization of ∼20,000 neuronal clocks Suprachiasmatic Nucleus (SCN). While anatomical, molecular, and genetic approaches have revealed diverse cell types signaling mechanisms, network wiring that enables SCN cells to communicate synchronize remains unclear. To overcome challenges revealing functional connectivity fixed tissue, we developed MITE (Mutual Information & Transfer Entropy), an information theory approach infers directed cell-cell connections with high fidelity. By analyzing 3447 hours continuously recorded clock gene expression 9011 17 mice, found connectome was highly conserved bilaterally across sparse, organized into a dorsomedial ventrolateral module. most were local, discovered long-range ventral both dorsal SCN. Based on their connectivity, can be characterized as circadian signal generators, broadcasters, sinks, or bridges. For example, subset VIP neurons acts hubs generate signals critical daily neural network. Simulations experimentally inferred networks recapitulated stereotypical dorsal-to-ventral wave PER2 ability spontaneously synchronize, emergent dynamics are sculpted by connectivity. We conclude provides powerful method infer connectomes, architecture mediates synchrony space time mammalian Highlights MITE, method, accurately among cells. patterns spatially organize two regions function bridges information. One-third serve drive Key features mediate generation maintenance intercellular waves

Language: Английский

Estrogen‐mediated coupling via gap junctions in the suprachiasmatic nucleus DOI Creative Commons

Lina Schlaeger,

Iwona Olejniczak,

Marianne Lehmann

et al.

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 7, 2024

Abstract The circadian clock orchestrates many physiological and behavioural rhythms in mammals with 24‐h periodicity, through a hierarchical organisation, the central located suprachiasmatic nucleus (SCN) hypothalamus. circuits of SCN generate precision, relying on intrinsic coupling mechanisms, for example, neurotransmitters like arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), neuronal gamma‐aminobutyric acid (GABA) signalling astrocytes connected by gap junctions composed connexins (Cx). In female rodents, presence estrogen receptors (ERs) dorsal suggests an influence (E2) circuit timekeeping that could regulate rhythm coupling. To investigate this, we used explants together hypothalamic neurons astrocytes. First, showed E2 stabilised amplitude when rAVPs (receptor‐associated peptides) were inhibited. However, phase delay induced VIPAC2 (VIP receptors) inhibition remained unaffected E2. We then exerted its effects via ERβ (estrogen receptor beta), resulting increased expression Cx36 Cx43 . Notably, specific both resulted significant reduction within SCN. Remarkably, restored period inhibited but not inhibition. This implies network between neurons, responsible SCN, can be reinforced conclusion, these findings provide new insights into how regulates ex vivo ERβ‐dependent manner, underscoring crucial role fortifying SCN's rhythm.

Language: Английский

Citations

4
Understanding the mechanistic interlink between circadian misalignment and heart disease in night shift workers: Therapeutic role of behavioral interventions DOI

Jad Bou Serhal,

Mohammad Fayyad‐Kazan, Colette S. Kabrita

et al.

Sleep And Breathing, Journal Year: 2025, Volume and Issue: 29(1)

Published: Feb. 18, 2025

Language: Английский

Citations

0
Selective changes in vasopressin neurons and astrocytes in the suprachiasmatic nucleus of Prader–Willi syndrome subjects DOI Creative Commons
Felipe Corrêa‐da‐Silva, Jari B. Berkhout,

PC Schouten

et al.

Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

The hypothalamic suprachiasmatic nucleus (SCN) hosts the central circadian pacemaker and regulates daily rhythms in physiology behavior. SCN is composed of peptidergic neuron populations expressing arginine vasopressin (AVP) vasoactive intestinal polypeptide (VIP), as well glial cells. Patients with Prader-Willi Syndrome (PWS) commonly experience disturbances, which are particularly evident their sleep/wake patterns. Using publicly available single-cell RNA sequencing data, we assessed cell-type specificity PWS-causative genes murine SCN, revealed differential presence PWS-related neural subpopulations. We then investigated neurons cells using immunohistochemistry postmortem hypothalami PWS subjects matched controls. profiled characterized by AVP VIP, astroglia fibrillary acid protein (GFAP), microglia marked ionized calcium-binding adapter molecule 1 (Iba1) NADPH oxidase 2 (NOX2). Our analysis an increased total number, neuronal density, relative staining intensity AVP-containing compared to controls while VIP-containing were unaltered. In contrast, GFAP-expressing astroglial significantly lower subjects. Moreover, did not detect any differences between Collectively, our findings show that selectively affects astrocytes SCN. As each these cell can affect rhythmicity biological clock machinery, disruption may contribute disturbances patients PWS.

Language: Английский

Citations

0
Circadian rhythm mechanism in the suprachiasmatic nucleus and its relation to the olfactory system DOI Creative Commons
Yusuke Tsuno, Michihiro Mieda

Frontiers in Neural Circuits, Journal Year: 2024, Volume and Issue: 18

Published: March 25, 2024

Animals need sleep, and the suprachiasmatic nucleus, center of circadian rhythm, plays an important role in determining timing sleep. The main input to nucleus is retinohypothalamic tract, with additional inputs from intergeniculate leaflet pathway, serotonergic afferent raphe, other hypothalamic regions. Within two major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons arginine-vasopressin (AVP)-positive neurons. VIP for light entrainment synchronization neurons, whereas AVP period determination. Output targets include hypothalamus (subparaventricular zone, paraventricular preoptic area, medial hypothalamus), thalamus (paraventricular thalamic nuclei), lateral septum. also sends information through several brain regions pineal gland. olfactory bulb thought be able generate a rhythm without nucleus. Some reports indicate that rhythms cortex exist absence but another report claims influence regulation by sensory than stimuli, including olfaction, has not been well studied further progress expected.

Language: Английский

Citations

3
In vivo recording of the circadian calcium rhythm in Prokineticin 2 neurons of the suprachiasmatic nucleus DOI Creative Commons

Kaito Onodera,

Yusuke Tsuno, Yuichi Hiraoka

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 9, 2023

Abstract Prokineticin 2 (Prok2) is a small protein expressed in subpopulation of neurons the suprachiasmatic nucleus (SCN), primary circadian pacemaker mammals. Prok2 has been implicated as candidate output molecule from SCN to control multiple rhythms. Genetic manipulation specific Prok2-producing would be powerful approach understanding their function. Here, we report generation Prok2-tTA knock-in mice expressing tetracycline transactivator (tTA) specifically and an application these vivo recording Ca 2+ rhythms neurons. First, efficient expression tTA was verified by crossing with EGFP reporter mice. were then used express fluorescent sensor record rhythm vivo. cells showed clear both light–dark constant dark conditions, peaks around midday. Notably, hours high nearly coincided rest period behavioral rhythm. These observations fit well predicted function pathway suppressing locomotor activity during daytime subjective daytime.

Language: Английский

Citations

4
The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice DOI Creative Commons

Brooke M. Van Loh,

Alexandra M. Yaw,

Joseph Breuer

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 22, 2023

Background The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information body and synchronize cell tissue level rhythms hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate output. Here we focus on vasoactive intestinal (VIP) expressing neurons SCN. VIP are known circadian reproductive function. Methods To specifically study generated novel knock out mouse line conditionally deleting enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in (Vax1 Vip ; Vax1 fl/fl :Vip Cre ). Results We found that females presented with lengthened estrous cycles, reduced circulating estrogen, increased depressive-like behavior. Further, males shortened period locomotor activity ex vivo period. On molecular level, shortening was driven, at least partially, direct regulatory role VAX1 clock genes Bmal1 Per2 . Interestingly, expression arginine vasopressin ( Avp ) paraventricular nucleus, which resulted corticosterone. AVP gonadotropin-releasing (GnRH) kisspeptin neurons. determine how neuroendocrine network impacted mice, assessed GnRH sensitivity challenge females, but not males, had an kisspeptin, leading luteinizing showed small, significant increase total sperm modest delay pubertal onset. Both male female mice were fertile litters comparable size frequency controls. Conclusion Together, these data identify as neurological overlap between timekeeping, reproduction, symptoms provide insight into

Language: Английский

Citations

4
Arginine vasopressin: Critical regulator of circadian homeostasis DOI
Yoshiaki Yamaguchi

Peptides, Journal Year: 2024, Volume and Issue: 177, P. 171229 - 171229

Published: April 23, 2024

Language: Английский

Citations

1
The Functional Connectome Mediating Circadian Synchrony in the Suprachiasmatic Nucleus DOI Creative Commons
K. L. Nikhil, Bharat Singhal, Daniel Granados‐Fuentes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Abstract Circadian rhythms in mammals arise from the spatiotemporal synchronization of ∼20,000 neuronal clocks Suprachiasmatic Nucleus (SCN). While anatomical, molecular, and genetic approaches have revealed diverse cell types signaling mechanisms, network wiring that enables SCN cells to communicate synchronize remains unclear. To overcome challenges revealing functional connectivity fixed tissue, we developed MITE (Mutual Information & Transfer Entropy), an information theory approach infers directed cell-cell connections with high fidelity. By analyzing 3447 hours continuously recorded clock gene expression 9011 17 mice, found connectome was highly conserved bilaterally across sparse, organized into a dorsomedial ventrolateral module. most were local, discovered long-range ventral both dorsal SCN. Based on their connectivity, can be characterized as circadian signal generators, broadcasters, sinks, or bridges. For example, subset VIP neurons acts hubs generate signals critical daily neural network. Simulations experimentally inferred networks recapitulated stereotypical dorsal-to-ventral wave PER2 ability spontaneously synchronize, emergent dynamics are sculpted by connectivity. We conclude provides powerful method infer connectomes, architecture mediates synchrony space time mammalian Highlights MITE, method, accurately among cells. patterns spatially organize two regions function bridges information. One-third serve drive Key features mediate generation maintenance intercellular waves

Language: Английский

Citations

0