Explain the contribution of cholinergic system in controlling different levels of activities

Respiration is altered during different stages of the sleep-wake cycle. We review the contribution of cholinergic systems to this alteration, with particular reference to the role of muscarinic acetylcholine receptors (MAchRs) during rapid eye movement (REM) sleep. Available evidence demonstrates that MAchRs have potent excitatory effects on medullary respiratory neurones and respiratory motoneurones, and are likely to contribute to changes in central chemosensitive drive to the respiratory control system. These effects are likely to be most prominent during REM sleep, when cholinergic brainstem neurones show peak activity levels. It is possible that MAchR dysfunction is involved in sleep-disordered breathing, such as obstructive sleep apnea.

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Cytokine production is necessary to protect against pathogens and promote tissue repair, but excessive cytokine release can lead to systemic inflammation, organ failure and death. Inflammatory responses are finely regulated to effectively guard from noxious stimuli. The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. The effect of glucocorticoids and other humoral mediators on inflammatory responses has been studied extensively in the past decades. In contrast, neural control of inflammation has only been recently described. We summarize autonomic regulation of local and systemic inflammation through the ‘cholinergic anti-inflammatory pathway’, a mechanism consisting of the vagus nerve and its major neurotransmitter, acetylcholine, a process dependent on the nicotinic acetylcholine receptor α7 subunit. We recapitulate additional sources of acetylcholine and their contribution to the inflammatory response, as well as acetylcholine regulation by acetylcholinesterase as a means to attenuate inflammation. We discuss potential therapeutic applications to treat diseases characterized by acute or chronic inflammation, including autoimmune diseases, and propose future research directions.

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