Afferent Projections to the Calca/CGRP-Expressing Parabrachial Neurons in Mice.

The parabrachial nucleus (PB), located in the dorsolateral pons, contains primarily glutamatergic neurons that regulate responses to a variety of interoceptive and cutaneous sensory signals. One lateral PB subpopulation expresses the Calca gene, which codes for the neuropeptide calcitonin gene-related peptide (CGRP). These PB neurons relay signals related to threatening stimuli such as hypercarbia, pain, and nausea, yet their inputs and their neurochemical identity are only partially understood.

Afferent projections to the /CGRP-expressing parabrachial neurons in mice.

The parabrachial nucleus (PB), located in the dorsolateral pons, contains primarily glutamatergic neurons which regulate responses to a variety of interoceptive and cutaneous sensory signals. The lateral PB subpopulation expressing the gene which produces the neuropeptide calcitonin gene-related peptide (CGRP) relays signals related to threatening stimuli such as hypercarbia, pain, and nausea, yet the afferents to these neurons are only partially understood. We mapped the afferent projections to the lateral part of the PB in mice using conventional cholera toxin B subunit (CTb) retrograde tracing, and then used conditional rabies virus retrograde tracing to map monosynaptic inputs specifically targeting the PB neurons.

Adenosine A receptors and sleep.

Adenosine, a known endogenous somnogen, induces sleep via A and A receptors. In this chapter, we review the current knowledge regarding the role of the adenosine A receptor and its agonists, antagonists, and allosteric modulators in sleep-wake regulation. Although many adenosine A receptor agonists, antagonists, and allosteric modulators have been identified, only a few have been tested to see if they can promote sleep or wakefulness.

Allosteric Modulation of Adenosine A Receptors as a New Therapeutic Avenue.

The therapeutic potential of targeting adenosine A receptors (ARs) is immense due to their broad expression in the body and central nervous system. The role of ARs in cardiovascular function, inflammation, sleep/wake behaviors, cognition, and other primary nervous system functions has been extensively studied. Numerous AR agonist and antagonist molecules are reported, many of which are currently in clinical trials or have already been approved for treatment.

Therapeutic potential of serotonin 4 receptor for chronic depression and its associated comorbidity in the gut.

The latest estimates from world health organization suggest that more than 450 million people are suffering from depression and other psychiatric conditions. Of these, 50-60% have been reported to have progression of gut diseases. In the last two decades, researchers introduced incipient physiological roles for serotonin (5-HT) receptors (5-HTRs), suggesting their importance as a potential pharmacological target in various psychiatric and gut diseases.

Acute Social Defeat Stress Increases Sleep in Mice.

Social conflict is a major source of stress in humans. Animals also experience social conflicts and cope with them by stress responses that facilitate arousal and activate sympathetic and neuroendocrine systems. The effect of acute social defeat (SoD) stress on the sleep/wake behavior of mice has been reported in several models based on a resident-intruder paradigm.

Extracellular adenosine and slow-wave sleep are increased after ablation of nucleus accumbens core astrocytes and neurons in mice.

Sleep and wakefulness are controlled by a wide range of neuronal populations in the mammalian brain. Activation of adenosine A receptor (AR)-expressing neurons in the nucleus accumbens (NAc) core promotes slow-wave sleep (SWS). The neuronal mechanism by which activation of NAc AR neurons induces SWS, however, is unknown.

The Leptomeninges Produce Prostaglandin D Involved in Sleep Regulation in Mice.

Injection of nanomolar amounts of prostaglandin D (PGD) into the rat brain has dose and time-dependent somnogenic effects, and the PGD-induced sleep is indistinguishable from physiologic sleep. Sleep-inducing PGD is produced in the brain by lipocalin-type PGD synthase (LPGDS). Three potential intracranial sources of LPGDS have been identified: oligodendrocytes, choroid plexus, and leptomeninges.

Enhancing endogenous adenosine A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function.

Insomnia is one of the most common sleep problems with an estimated prevalence of 10%-15% in the general population. Although adenosine A receptor (AR) agonists strongly induce sleep, their cardiovascular effects preclude their use in treating sleep disorders. Enhancing endogenous AR signaling, however, may be an alternative strategy for treating insomnia, because adenosine levels in the brain accumulate during wakefulness.