Activation of Pontine and Medullary Motor Inhibitory Regions Reduces Discharge in Neurons Located in the Locus Coeruleus and the Anatomical Equivalent of the Midbrain Locomotor Region

Abstract

Activation of the pontine inhibitory area (PIA) including the middle portion of the pontine reticular nucleus, oral part (PnO), or the gigantocellular reticular nucleus (Gi) suppresses muscle tone in decerebrate animals. The locus coeruleus (LC) and midbrain locomotor region (MLR) have been implicated in the facilitation of muscle tone. In the current study we investigated whether PIA and Gi stimulation causes changes in activity in these brainstem motor facilitatory systems. PIA stimulation evoked bilateral muscle tone suppression and inhibited 26 of 28 LC units and 33 of 36 tonically active units located in the anatomical equivalent of the MLR (caudal half of the cuneiform nucleus and the pedunculopontine tegmental nucleus). Gi stimulation evoked bilateral suppression of hindlimb muscle tone and inhibited 20 of 35 LC units and 24 of 24 neurons located in the MLR as well as facilitated 11 of 35 LC units. GABA and glycine release in the vicinity of LC was increased by 20-40% during ipsilateral PnO stimulation inducing hindlimb muscle tone suppression on the same side of the body. We conclude that activation of pontine and medullary inhibitory regions produces a coordinated reduction in the activity of the LC units and neurons located in the MLR related to muscle tone facilitation. The linkage between activation of brainstem motor inhibitory systems and inactivation of brainstem facilitatory systems may underlie the reduction in muscle tone in sleep as well as the modulation of muscle tone in the isolated brainstem. Key words: muscle tone; gigantocellular reticular nucleus; pontine inhibitory area; locus coeruleus; subcoeruleus nucleus; midbrain locomotor region; REM sleep; GABA; glycine; microdialysisPrevious studies performed in decerebrate cats have shown that electrical stimulation and chemical excitation of the medial pontine reticular formation and magnocellularis and paramedianus nuclei of the medulla induced bilateral muscle atonia (Lai and Siegel, 1988, 1990a,b, 1991. In decerebrate rats, stimulation sites inducing bilateral muscle tone inhibition are located in middle portions of the oral and caudal pontine reticular nuclei and gigantocellular and dorsal gigantocellular reticular nuclei (Hajnik et al., 2000). These pontine and medullary inhibitory regions are elements of a brainstem inhibitory system hyperpolarizing spinal motoneurons (Magoun and Rhines, 1946;Jankowska et al., 1968;Takakusaki et al., 1994) and participating in rapid eye movement (REM) sleep atonia (Sakai et al., 1979;Chase and Morales, 1990; Lai and Siegel, 1990a,b). Lesions of the pontine inhibitory area (PIA) (Jouvet and Delorme, 1965;Henley and Morrison, 1974) and medial medulla (Schenkel and Siegel, 1989;Holmes and Jones, 1994) prevent the normal suppression of muscle tone in REM sleep, resulting in REM sleep without atonia. The REM sleep behavior disorder (Schenck and Mahowald, 1991) seen particularly in elderly males is the human analog of REM sleep without atonia.Pharmacological, electrophysiological, and behavioral studies indi...

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