GABAergic signalling in the suprachiasmatic nucleus is required for coherent circadian rhythmicity.

The suprachiasmatic nucleus is the circadian pacemaker of the mammalian brain. Suprachiasmatic nucleus neurons display synchronization of their firing frequency on a circadian timescale, which is required for the pacemaker function of the suprachiasmatic nucleus. However, the mechanisms by which suprachiasmatic nucleus neurons remain synchronized in vivo are poorly understood, although synaptic communication is considered indispensable.

A hypothalamic circuit for circadian regulation of corticosterone secretion.

The secretion of cortisol in humans and corticosterone (Cort) in rodents follows a daily rhythm which is important in readying the individual for the daily active cycle and is impaired in chronic depression. This rhythm is orchestrated by the suprachiasmatic nucleus (SCN) which governs the activity of neurons in the paraventricular nucleus of the hypothalamus that produce the corticotropin-releasing hormone (PVH neurons). The dorsomedial nucleus of the hypothalamus (DMH) serves as a crucial intermediary, being innervated by the SCN both directly and via relays in the subparaventricular zone, and projecting axons to the PVH, thereby exerting influence over the cortisol/corticosterone rhythm.

Lateral parabrachial FoxP2 neurons regulate respiratory responses to hypercapnia.

About half of the neurons in the parabrachial nucleus (PB) that are activated by CO are located in the external lateral (el) subnucleus, express calcitonin gene-related peptide (CGRP), and cause forebrain arousal. We report here, in male mice, that most of the remaining CO-responsive neurons in the adjacent central lateral (PBcl) and Kölliker-Fuse (KF) PB subnuclei express the transcription factor FoxP2 and many of these neurons project to respiratory sites in the medulla. PBcl neurons show increased intracellular calcium during wakefulness and REM sleep and in response to elevated CO during NREM sleep.

A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution.

The "dorsal pons", or "dorsal pontine tegmentum" (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei.

A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution.

The "dorsal pons", or "dorsal pontine tegmentum" (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei.

Beyond the symptom: the biology of fatigue.

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.

Prolonged activation of EP3 receptor-expressing preoptic neurons underlies torpor responses.

Many species use a temporary drop in body temperature and metabolic rate (torpor) as a strategy to survive food scarcity. A similar profound hypothermia is observed with activation of preoptic neurons that express the neuropeptides Pituitary Adenylate-Cyclase-Activating Polypeptide (PACAP), Brain Derived Neurotrophic Factor (BDNF), or Pyroglutamylated RFamide Peptide (QRFP), the vesicular glutamate transporter, Vglut2 or the leptin receptor (LepR), estrogen 1 receptor (Esr1) or prostaglandin E receptor 3 (EP3R) in mice. However, most of these genetic markers are found on multiple populations of preoptic neurons and only partially overlap with one another.

Lateral parabrachial FoxP2 neurons regulate respiratory responses to hypercapnia.

Although CGRP neurons in the external lateral parabrachial nucleus (PBel neurons) are critical for cortical arousal in response to hypercapnia, activating them has little effect on respiration. However, deletion of all Vglut2 expressing neurons in the PBel region suppresses both the respiratory and arousal response to high CO2. We identified a second population of non-CGRP neurons adjacent to the PBel group in the central lateral, lateral crescent and Kölliker-Fuse parabrachial subnuclei that are also activated by CO2 and project to the motor and premotor neurons that innvervate respiratory sites in the medulla and spinal cord.

Human Brainstem and Cerebellum Atlas: Chemoarchitecture and Cytoarchitecture Paired to MRI.

Lesion localization is the basis for understanding neurologic disease, which is predicated on neuroanatomical knowledge carefully cataloged from histology and imaging atlases. However, it is often difficult to correlate clinical images of brainstem injury obtained by MRI scans with the details of human brainstem neuroanatomy represented in atlases, which are mostly based on cytoarchitecture using Nissl stain or a single histochemical stain, and usually do not include the cerebellum. Here, we report a high-resolution (200 μm) 7T MRI of a cadaveric male human brainstem and cerebellum paired with detailed, coregistered histology (at 2 μm single-cell resolution) of the immunohistochemically stained cholinergic, serotonergic, and catecholaminergic (dopaminergic, noradrenergic, and adrenergic) neurons, in relationship to each other and to the cerebellum.

Orexin neurons inhibit sleep to promote arousal.

Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus.

Genetic identification of preoptic neurons that regulate body temperature in mice.

There has been an explosion recently in our understanding of the neuronal populations in the preoptic area involved in thermoregulation of mice. Recent studies have identified several genetically specified populations of neurons predominantly in the median preoptic nucleus (MnPO) but spreading caudolaterally into the preoptic area that regulate body temperature. .

Median preoptic GABA and glutamate neurons exert differential control over sleep behavior.

Previous studies suggest that the median preoptic nucleus (MnPO) of the hypothalamus plays an important role in regulating the wake-sleep cycle and, in particular, homeostatic sleep drive. However, the precise cellular phenotypes, targets, and central mechanisms by which the MnPO neurons regulate the wake-sleep cycle remain unknown. Both excitatory and inhibitory MnPO neurons innervate brain regions implicated in sleep promotion and maintenance, suggesting that both cell types may participate in sleep control.

Chronic circadian disruption on a high-fat diet impairs glucose tolerance.

Background: Nearly 14% of Americans experience chronic circadian disruption due to shift work, increasing their risk of obesity, diabetes, and other cardiometabolic disorders. These disorders are also exacerbated by modern eating habits such as frequent snacking and consumption of high-fat foods.

Methods: We investigated the effects of recurrent circadian disruption (RCD) on glucose metabolism in C57BL/6 mice and in human participants exposed to non-24-h light-dark (LD) schedules vs.

Hypothalamic Hamartomas: Evolving Understanding and Management.

Hypothalamic hamartomas (HH) are rare, basilar developmental lesions with widespread comorbidities often associated with refractory epilepsy and encephalopathy. Imaging advances allow for early, even prenatal, detection. Genetic studies suggest mutations in and other patterning genes are involved in HH pathogenesis.

The search for thermoregulatory neurons is heating up.

Recent studies have shown that the median preoptic area contains a population of neurons expressing an array of fast neurotransmitters and receptors that collectively cause a fall in body temperature in response to environmental warming or depleted energy stores. In this issue of Cell Metabolism, Piñol et al. (2021) identify a separate population of median preoptic neurons that are responsible for cold defense and cause stress-related hyperthermia.

The intermediate nucleus in humans: Cytoarchitecture, chemoarchitecture, and relation to sleep, sex, and Alzheimer disease.

The intermediate nucleus of Brockhaus (INH), also known as the interstitial nucleus of the anterior hypothalamus-1 of Allen and Gorski (INAH-1), the sexually dimorphic nucleus of Swaab and colleagues (SDN), and the ventrolateral preoptic nucleus of Saper and colleagues (VLPO), is a cluster of largely galanin-expressing neurons in the lateral preoptic area, at the level of the crossing of the anterior commissure and dorsal to the supraoptic nucleus. The number of Nissl-stained neurons in the INH has been reported to be larger in men than women and to decrease with aging, although these findings have been controversial, in part because of differences in patient populations and methods used to assess the nucleus. However, recent studies have confirmed that the number of galanin-immunoreactive INH neurons is larger in men than women and decreases with age and have reported further loss with Alzheimer disease.