Localization of pontine PGO wave generation sites and their anatomical projections in the rat

Abstract

A number of experimental and theoretical reports have suggested that the ponto-geniculo-occipital (PGO) wave-generating cells are involved in the generation of rapid eye movement (REM) sleep and REM sleep dependent cognitive functions. No studies to date have examined anatomical projections from PGO-generating cells to those brain structures involved in REM sleep generation and cognitive functions. In the present study, pontine PGO wave-generating sites were mapped by microinjecting carbachol in 74 sites of the rat brainstem. Those microinjections elicited PGO waves only when made in the dorsal part of the nucleus subcoeruleus of the pons. In six rats, the anterograde tracer biotinylated dextran amine (BDA) was microinjected into the physiologically identified cholinoceptive pontine PGO-generating site to identify brain structures receiving efferent projections from those PGO-generating sites. In all cases, small volume injections of BDA in the cholinoceptive pontine PGO-generating sites resulted in anterograde labeling of fibers and terminals in many regions of the brain. The most important output structures of those PGO-generating cells were the occipital cortex, entorhinal cortex, piriform cortex, amygdala, hippocampus, and many other thalamic, hypothalamic, and brainstem nuclei that participate in the generation of REM sleep. These findings provide anatomical evidence for the hypothesis that the PGO-generating cells in the pons could be involved in the generation of REM sleep. Since PGO-generating cells project to the entorhinal cortex, piriform cortex, amygdala, and hippocampus, these PGO-generating cells could also be involved in the modulation of cognitive functions.

Electrophysiological characterization of neurons in the dorsolateral pontine rapid-eye-movement sleep induction zone of the rat: Intrinsic membrane properties and responses to carbachol and orexins

“…In the cat, PGO burst neurons with a short lead time (< 100 ms) prior to P-waves have been recorded in the parabrachial region which borders and overlaps with the subcoeruleus area recorded in this study in the rat (McCarley et al, 1978;Sakai and Jouvet, 1980;Nelson et al, 1983;Steriade et al, 1990;Datta and Hobson, 1994). Although neurons with these properties have also been recorded in other areas of the brainstem reticular formation, they seem to be particularly concentrated in the SubC area, which is consistent with this area being the best site to record P-waves Farber et al, 1980;Kaufman and Morrison, 1981) and the most sensitive site for carbachol to cause an enhancement of P-wave frequency (Datta et al, 1998).…”

“…However, since we have shown that these neurons are hyperpolarized by carbachol and it has been previously demonstrated that carbachol causes a long-lasting enhancement of PGO waves in both rats and cats (Datta et al, 1991a;Datta et al, 1998) we suggest that this hyperpolarization is likely to be caused by acetylcholine released from neighbouring cholinergic neurons in the laterodorsal tegmental nucleus (LDT). This would also be consistent with the block of carbachol induced PGO waves in the cat by a M 2 receptor antagonist (Datta et al, 1993) since activation of M 2 receptors usually causes a hyperpolarizing response similar to the one we have observed here (Egan and North, 1986;Gerber et al, 1991).…”

“…Neurons in the SubC area neighbouring the brachium conjunctivum fire synchronized bursts preceding and phase-locked to PGO waves (McCarley et al, 1978;Sakai and Jouvet, 1980;Steriade et al, 1990;Datta, 1997), the pontine component of which (P-waves) can be recorded in rats using low-resistance electrodes Kaufman and Morrison, 1981;Datta et al, 1998). Small injections of carbachol into the SubC in the rat elicits an increase in the frequency of PGO waves which is correlated with a facilitation of learning and memory formation (Mavanji and Datta, 2003;Datta et al, 2004).…”

Human brain activity time-locked to rapid eye movements during REM sleep

“…It is well known that there are anatomical and physiological correlations between the amygdala and the pons, where the PGO wave generator is located (Calvo and Fernandez-Guardiola 1984;Datta et al 1998) and that the time interval between PGO waves and REMs is on the order of tens of milliseconds in neurophysiological studies using animals (Datta and Hobson 1994). In contrast, the BOLD response of the PGO areas started several seconds before the occurrence of REMs in the present study.…”

Cholinergic and glutamatergic agonists induce gamma frequency activity in dorsal subcoeruleus nucleus neurons

“…Nuclei located in the pons, including the dorsal subcoeruleus nucleus (SubCD), are critical for generation of REM sleep (3,5,6,12,25,29,44). Lesion of this area produced REM sleep without muscle atonia or ponto-geniculo-occipital (PGO) waves (21,26,29,33), or diminished REM sleep (24).…”