Carbachol Models of REM Sleep

            The rapid eye movement (REM) stage of sleep is characterized by cortical activation, hippocampal theta rhythm, rapid eye movements (hence the name), absence of activity in postural muscles (atonia), variable breathing and arterial blood pressure and, at least in subjects with collapsible upper airway, a profound suppression of activity in upper airway muscles. Many of these phenomena can be produced in experimental animals pharmacologically by local microinjections of a cholinergic agonist, carbachol, into a discrete region of the pontine reticular formation. This approach allows one to study the central neural mechanisms underlying the generation of distinct hallmarks of REM sleep. 

In decerebrate cats, pontine injections of carbachol produce postural atonia, depression of upper airway muscle tone and eye movements:

 

 

 

In this model, as in natural REM sleep, carbachol-induced atonia is associated with suppression of activity in medullary serotonin-containing neurons.

In urethane-anesthetized rats, pontine carbachol injections can be used to repeatedly trigger short (2-4 min) episodes of cortical activation, hippocampal theta-like rhythm, suppression of activity in upper airway (hypoglossal) motoneurons, and silencing of pontine noradrenergic cells:

 

   

The REM sleep-like episodes are elicited in urethane-anesthetized rats from a discrete site within the dorsomedial pontine tegmentum: