Brainstem cholinergic modulation of muscle tone in infant rats

Abstract

In week-old rats, lesions of the dorsolateral pontine tegmentum (DLPT) and nucleus pontis oralis (PnO) have opposing effects on nuchal muscle tone. Specifically, pups with DLPT lesions exhibit prolonged bouts of nuchal muscle atonia (indicative of sleep) and pups with PnO lesions exhibit prolonged bouts of high nuchal muscle tone (indicative of wakefulness). Here we test the hypothesis that nuchal muscle tone is modulated, at least in part, by cholinergically mediated interactions between these two regions. First, in unanesthetized pups, we found that chemical infusion of the cholinergic agonist carbachol (22 mm, 0.1 microL) within the DLPT produced high muscle tone. Next, chemical lesions of the PnO were used to produce a chronic state of high nuchal muscle tone, at which time the cholinergic antagonist scopolamine (10 mm, 0.1 microL) was infused into the DLPT. Scopolamine effectively decreased nuchal muscle tone, thus suggesting that lesions of the PnO increase muscle tone via cholinergic activation of the DLPT. Using 2-deoxyglucose autoradiography, metabolic activation throughout the DLPT was observed after PnO lesions. Finally, consistent with the hypothesis that PnO inactivation produces high muscle tone, infusion of the sodium channel blocker lidocaine (2%) into the PnO of unanesthetized pups produced rapid increases in muscle tone. We conclude that, even early in infancy, the DLPT is critically involved in the regulation of muscle tone and behavioral state, and that its activity is modulated by a cholinergic mechanism that is directly or indirectly controlled by the PnO.

Brainstem and hypothalamic regulation of sleep pressure and rebound in newborn rats.

“…These results are also consistent with recording and lesion studies, performed in P8 rats, that demonstrate brainstem contributions to spontaneous sleep and wakefulness (Gall, Poremba, & Blumberg, 2007; Karlsson et al , 2005). Thus, at least some of the neural mechanisms that underlie deprivation-induced wakefulness in adults are functional as early as P2.…”

“…Using these methods in neonatal rats, we have shown that brainstem (Gall et al , 2007; Karlsson et al , 2005) and forebrain (Karlsson et al , 2004; Mohns et al , 2006) mechanisms modulate sleep and wakefulness and that these mechanisms appear identical to those identified in adults. Here we further demonstrate that brainstem and hypothalamic nuclei associated with sleep pressure and rebound – regulatory processes that are considered among the defining features of sleep (Campbell & Tobler, 1984; Hendricks, Sehgal, & Pack, 2000) – are already functioning in infants as young as P2.…”

Developmental nicotine exposure alters cholinergic control of respiratory frequency in neonatal rats

“…). The idea was to selectively stimulate nAChRs, while also mimicking the surge in ACh from cholinergic neurons, such as occurs with arousal (Phillis, ), upon the transition from sleep to wakefulness (Jones, ; Gall et al, ), in states of vigilance (Lai and Siegel, ; Gall et al, ; Roman‐Liu et al, ) and during exercise (Nakajima et al, ). In control animals, addition of ACh in the presence of atropine caused a rapid increase in frequency that peaked in 6–7 min and then began a slow decline towards baseline levels, with a further reduction during drug washout (Fig.…”

Theory of Mind: Towards an Evolutionary Theory

“…One possibility is that autistic children suffer from a deficit in cholinergic neurotransmission, as this type of neurotransmission has been shown to play a central role in the regulation of muscle tone. Gall et al (2007), for example, found that muscle tone in rats, and especially in the neck and spine, is controlled by the interaction between two cholinergic nuclei: the nucleus pontis oralis and the dorsolateral pontine tegmentum. Takakusaki et al (2003Takakusaki et al ( , 2004 showed that postural muscle tone and locomotion in cats is controlled by the cholinergic pedunculopontine tegmental nucleus.…”