Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat

Abstract

Microinjection of cholinergic agonists in a dorsolateral part of the mesopontine tegmentum has been shown to induce a rapid eye movement (REM) sleep-like state. Physiological evidence indicates that not only acetylcholine but also various amine transmitters, including those implicated in behavioral state regulation, affect neuronal activity in this region of the pontine reticular formation. In the present study, sources of select aminergic and cholinergic inputs to this REM sleep induction zone were identified and quantitatively analyzed by using fluorescence retrograde tracing combined with immunofluorescence in the rat. In addition to previously demonstrated cholinergic projections from the pedunculopontine and laterodorsal tegmental nuclei, the REM sleep induction zone received various aminergic inputs that originated in widely distributed regions of the brainstem and hypothalamus. Serotoninergic afferents represented a mean of 44% of all aminergic/cholinergic source neurons projecting to the REM sleep induction zone, which was comparable to the mean percentage of 39% represented by cholinergic afferent neurons. The serotoninergic afferents originated from the raphe nuclei at all brainstem levels, with heavier projections from the pontine than from the medullary raphe nuclei. Unexpectedly, an additional major serotoninergic input was provided by serotoninergic neurons in the nucleus prosupralemniscus (B9). Noradrenergic afferent neurons represented a mean of 14% of all aminergic/cholinergic source neurons, which was only about one-third of the mean percentage of either cholinergic or serotoninergic source neurons. These noradrenergic projection neurons were located not only in the locus ceruleus (8%) but also in the lateral tegmentum, including the A5 (4%) and A7 (2%) cell groups. Histaminergic neurons in the tuberomammillary hypothalamic nucleus represented a minor group of afferent neurons (3%), and a still smaller input came from adrenergic C1 neurons. The pattern of these transmitter-specific afferent connections appeared to be similar regardless of the longitudinal level within the REM sleep induction zone. The present results are consistent with previous behavioral and physiological evidence for a role of the pontine REM sleep induction zone in triggering REM sleep. The regulation of REM sleep induction would be best understood in terms of a state-dependent interplay of cholinergic, serotoninergic, and other inputs all acting convergently upon neurons in the REM sleep-inducing region of the pontine reticular formation.

Neurobiological basis of state-dependent control of motor behaviors

“…Neuroanatomical studies have revealed that the cholinoceptive cells in the PRF receive cholinergic inputs from the LDT and the PPN (Semba, 1993;Lai et al, 1993), and serotonergic inputs from the dorsal raphe nucleus (Semba 1993) and dorsal tegmental area (Kobayashi et al, 1994) (Fig.3). How then, is postural muscle tone controlled by cholinergic-monoaminergic interaction acting on the PRF?…”

Modelo in vitro para el estudio del papel de la unión mesopontina en la generación del sueño de movimientos oculares rápidos y la vigilia

“…La combinación del marcaje retrógrado con la detección inmunohistoquímica para ChAT, buscó identificar las neuronas colinérgicas dentro del grupo de neuronas del LDT-PPT marcadas retrógradamente. Estos núcleos del tegmento pontino son considerados el principal origen de la inervación colinérgica del SNC en general y del PnO en particular (62) (63)(64) (65) . La utilización del procedimiento están-dar para la inmunodetección para ChAT mostró marcaje evidente en las motoneuronas del NM V así como en neuronas del LDT-PPT que no mostraron marcaje retrógrado (Figs.…”

“…4C1 y C3) sugiriendo que neuronas no colinérgicas, presumiblemente glutamatérgicas o GABAérgicas, inervan el PnO y están presentes en la rodaja de la unión ponto-mesencefálica. Evidencias en este sentido han sido aportadas por otros autores (65) (66)(67) aún Figura 4. Neuronas colinérgicas y no colinérgicas del LDT-PPT inervan al PnO en la rodaja mesopontina.…”

Possible Contribution of the Basal Ganglia Brainstem System to the Pathogenesis of Parkinson’s Disease

“…This inhibitory system is also thought to induce muscular atonia during the rapid eye movement (REM) sleep (Chase & Morales 1990;Takakusaki et al, 1993). There are serotonergic projections to the PPN (Honda & Semba, 1994) and to the cholinoceptive area of the PRF (Semba, 1993). Serotonergic projections to the PPN likely inhibit cholinergic neurons (Leonald & Llinás, 1994), and those to the PRF may reduce activity of the inhibitory system (Takakusaki et al, 1994).…”