Cholinergic brainstem neurons

Huitron-Resendiz, S., Kristensen, M. P Sanchez-Alavez, M. et al. (2005). Urotensin II modulates rapid eye movement sleep through activation of brainstem cholinergic neurons. J. Neurosci 25, 5465-74. 

Adenosine has been proposed to induce sleep by inhibiting cholinergic neurons of the BFB and the brainstem. In this respect, adenosine and the adenosine transport inhibitor NBTI decrease the discharge rate of BFB neurons during W, whereas the adenosine Ai receptor antagonist CPDX induces the opposite effects (Alam et al., 1999 Strecker et al., 2000). In addition, perfusion of adenosine into... 

I and II and also layers IV. Activity of the basal forebrain neurons is necessary for maintaining wakefulness and, functions of these and brainstem cholinergic nuclei include arousal, selective attention and REM sleep (Ch. 2). 

Mesulam MM, Mufson EJ, Levey AI, et al Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immuno histochemistry and acetylcholinesterase histochemistry. Neuroscience 12 669-686, 1984... 

Some features of the cholinergic system are germane to this question. Rather than projecting directly and diffusely to forebrain sectors, the brainstem cholinergic projections are both more limited in distance and more precisely targeted—they project to the ipsilateral thalamus and sub thalamus. From the basal forebrain, other cholinergic neurons project to the cortex. 

It is important to emphasise that a lesion of the reticular system disrupts a number of afferent inputs to the cortex. Particularly important in this respect are the mono-aminergic (especially noradrenaline, 5-HT and histamine) and cholinergic pathways. When the ascending inputs from these neurons are destroyed, sleep is passive and not at all like natural sleep which, as detailed above, has distinct phases and depends on brainstem influences on cortical function. How these different neurotransmitters might influence sleep and arousal will be considered next. 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

Figure 3.1 Schematic representation of communication between pontine cholinergic REM-ON, NA-ergic REM-OFF and GABA-ergic neurons in the brainstem and influence of brainstem wake- and sleep-inducing areas on REM-ON and REM-OFF neurons for the regulation of REM sleep. Refer to the text for details. The abbreviations are same as in the text (+) indicates excitation and (—) indicates inhibition.

Losier, B. J. Semba, K. (1993). Dual projections of single cholinergic and aminergic brainstem neurons to the thalamus and basal forebrain in the rat. Brain Res. 

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