Pontine cholinergic reticular mechanisms cause state-dependent changes in the discharge of parabrachial neurons

Abstract

The present study examined the hypothesis that cholinoceptive reticular mechanisms in the gigantocellular tegmental field (FTG) of the medial pontine reticular formation cause state-dependent changes in the discharge of parabrachial neurons. In chronically implanted, unanesthetized cats, extracellular recordings were made from nonrespiratory and respiratory neurons in the parabrachial nuclear complex (PBNC) during the natural sleep-wake cycle and during the rapid eye movement (REM) sleeplike state caused by FTG microinjection of carbachol or neostigmine. PBNC cells that increased discharge during natural REM sleep (REM-on cells) revealed similar increased discharge during the carbachol-induced REM sleeplike state (DCarb). Cells that decreased discharge in natural REM sleep (REM-off cells) displayed decreased discharge during both DCarb and the neostigmine-induced REM sleeplike states. The limited sample of parabrachial respiratory neurons revealed significantly diminished discharge during the cholinergically induced REM sleeplike state. Thus cholinoceptive mechanisms localized to specific regions of the pontine reticular formation can cause state-dependent changes in the firing rates of respiratory and nonrespiratory neurons in the PBNC.

Herbs for the Treatment of Insomnia

“…REM-on cholinergic neurons in the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei have high charge rates during wakefulness and REM sleep, and low discharge rates during NREM sleep. The norepinephrine and serotonin REM-off cells, which are excited by orexin neurons during wakefulness, start to wane in activity, which gradually release the cholinergic REM-on cells from their inhibitory effects (Gilbert and Lydic, 1994;Harris, 2005).…”

A role for the Kölliker-Fuse nucleus in cholinergic modulation of breathing at night during wakefulness and NREM sleep

“…Evidence of projections in the reverse direction, from the PRG to the mPRF, is provided by microinjection of fluorescent dyes into the PRG, resulting in ipsi-and contralateral positive regions in the mPRF as well as in the dorsal respiratory group and ventral respiratory group in the medulla (20). However, studies of the connectivity between brain stem respiratory neurons performed using chronically implanted arrays of microelectrodes emphasized "a sparse distribution of functional connections," which suggests that interactions between brain stem neurons include less direct pathways (29,32).Through interactions between brain stem respiratory neurons, PRG neurons contribute not only to respiratory phase switching (7,10,11,36) but also to multiple aspects of ventilatory control, including a postulated critical role in dampening respiratory instabilities during sleep (7,14,16,20,24). Many of the concepts regarding the role of cholinergic modulation of breathing during sleep are based on studies during REM sleep induced by cholinergic mimetics.…”

“…Microadministration of the cholinergic agonists carbachol (mixed cholinergic agonist), bethanechol (muscarinic agonist), and neostigmine (acetylcholine esterase inhibitor) into the mPRF are all known to generate this effect (1,2,18,22,27), whereas the muscarinic antagonist atropine can block this effect (1). Indeed, mPRF cholinoceptive mechanisms can cause state-dependent changes in the firing rates of respiratory neurons in the parabrachial nuclei (16). These studies provide evidence of anatomic connectivity from the mPRF to the pontine respiratory group (PRG).…”

“…Through interactions between brain stem respiratory neurons, PRG neurons contribute not only to respiratory phase switching (7,10,11,36) but also to multiple aspects of ventilatory control, including a postulated critical role in dampening respiratory instabilities during sleep (7,14,16,20,24). Many of the concepts regarding the role of cholinergic modulation of breathing during sleep are based on studies during REM sleep induced by cholinergic mimetics.…”

Neuronal activity within the ventrolateral periaqueductal gray during simulated hemorrhage in conscious rabbits

“…The majority (56%) of vlPAG neurons did not appear to respond to simulated hemorrhage. Of the 28 responsive vlPAG neurons, 11 showed an abrupt change in firing frequency during the time interval preceding the onset of hypotension; 13 responded after the onset of hypotension; and 4 showed a consistent direction of change across the entire simulated hemorrhage. Thus 24 (38%) of the vlPAG neurons recorded responded at a time consistent with a contribution to the hypotension associated with simulated hemorrhage.…”