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.

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.

Opioids, sleep, analgesia and respiratory depression: Their convergence on Mu (μ)-opioid receptors in the parabrachial area.

Opioids provide analgesia, as well as modulate sleep and respiration, all by possibly acting on the μ-opioid receptors (MOR). MOR's are ubiquitously present throughout the brain, posing a challenge for understanding the precise anatomical substrates that mediate opioid induced respiratory depression (OIRD) that ultimately kills most users. Sleep is a major modulator not only of pain perception, but also for changing the efficacy of opioids as analgesics.

The retrotrapezoid nucleus and the neuromodulation of breathing.

Breathing is regulated by a host of arousal and sleep-wake state-dependent neuromodulators to maintain respiratory homeostasis. Modulators such as acetylcholine, norepinephrine, histamine, serotonin (5-HT), adenosine triphosphate (ATP), substance P, somatostatin, bombesin, orexin, and leptin can serve complementary or off-setting functions depending on the target cell type and signaling mechanisms engaged. Abnormalities in any of these modulatory mechanisms can destabilize breathing, suggesting that modulatory mechanisms are not overly redundant but rather work in concert to maintain stable respiratory output.

Lipoatrophy-Associated Insulin Resistance and Hepatic Steatosis are Attenuated by Intake of Diet Rich in Omega 3 Fatty Acids.

Scope: Glucose homeostasis and progression of nonalcoholic fatty liver disease (NAFLD) and hepatomegaly in severe lipoatrophic mice and their modulation by intake of a diet rich in omega 3 (n-3) fatty acids (HFO) are evaluated.

Methods And Results: Severe lipoatrophic mice induced by PPAR-γ deletion exclusively in adipocytes (A-PPARγ KO) and littermate controls (A-PPARγ WT) are evaluated for glucose homeostasis and liver mass, proteomics, lipidomics, inflammation, and fibrosis. Lipoatrophic mice are heavier than controls, severely glucose intolerant, and hyperinsulinemic, and develop NAFLD characterized by increased liver glycogen, triacylglycerol, and diacylglycerol contents, mitotic index, apoptosis, inflammation, steatosis score, fibrosis, and fatty acid synthase (FAS) content and activity.

M4-muscarinic acetylcholine receptor into the pedunculopontine tegmental nucleus mediates respiratory modulation of conscious rats.

The pedunculopontine tegmental nucleus (PPTg) has been shown to have important functions relevant to the regulation of behavioral states and various motor control systems, including breathing control. The PPTg is considered an important nucleus in the mesopontine region with considerably cholinergic input to the ventral respiratory column. In addition, recent studies indicate that cholinergic innervation of the ventral respiratory column may play an important role in modulation of breathing.

Cholinergic neurons in the pedunculopontine tegmental nucleus modulate breathing in rats by direct projections to the retrotrapezoid nucleus.

Key Points: Cholinergic projections from the pedunculopontine tegmental nucleus (PPTg) to the retrotrapezoid nucleus (RTN) are considered to be important for sleep-wake state-dependent control of breathing. The RTN also receives cholinergic input from the postinspiratory complex. Stimulation of the PPTg increases respiratory output under control conditions but not when muscarinic receptors in the RTN are blocked.