Bulbospinal neurons implicated in mesopontine‐induced anesthesia are substantially collateralized

Abstract

Microinjection of pentobarbital or other gamma-aminobutyric acid type A receptor (GABA(A)-R) active anesthetics into a brainstem region in the rat that we have called the mesopontine tegmental anesthesia area (MPTA) induces a general anesthesia-like state that includes suppression of locomotor activity, loss of the righting reflex, atonia, antinociception, and apparent loss of consciousness. The suppression of muscle tone and of nocifensive spinal reflexes suggests a direct or indirect effect at the level of the spinal cord itself, an inference supported by anterograde tracing from the MPTA area. We have now used single and double retrograde tracing to characterize this bulbospinal pathway further. The MPTA contains the majority of all bulbospinal neurons present at mesopontine levels (65.8%). Many of these neurons, although not all, appear to have a highly collateralized projection pattern within the spinal cord. About 40% of the MPTA neurons that project to the lumbar spinal cord also have collaterals at cervical levels, and about 60% of those with projections to the ventral horn also have projections to the dorsal horn (at cervical levels). However, the large majority projects either ipsilaterally or contralaterally. Relatively few ( approximately 13%) send collaterals to both sides of the spinal cord. The pattern of connectivity revealed appears to be consistent with a system designed primarily to modulate motor and sensory functions globally, over the entire neuraxis, rather than regionally or segmentally.

Pontine reticulospinal projections in the neonatal mouse: Internal organization and axon trajectories

“…Liang et al () present images that suggest an ipsilateral predominance in the PnO following tracer injections in the lumbar spinal cord. Because a large proportion of pRS neurons in the PnO projects very medially (in the ipsilateral zone 1), it seems plausible that the contralateral predominance of the PnO projection reported by Liang et al () following cervical tracer injections and the nearly symmetrical laterality reported by Reiner et al () might have arisen from contamination of medially located axons on the side contralateral to the injection. This would label ipsilaterally projecting pRS neurons in the PnO contralateral to the tracer injection site, which would then be misinterpreted as projecting contralaterally.…”

“…Using the same dorsolateral funiculus‐targeted tracer applications, Watkins et al (1981) report bilateral labeling in PnC and contralateral labeling in PnO, again with only few pRS neurons labeled. In contrast to these studies, Reiner et al () report equal numbers of ipsilateral and contralateral pRS neurons regardless of whether injections were made at cervical, thoracic, or lumbar levels, and Liang et al () report a substantial contralateral predominance of projections from the PnO following tracer injections into the cervical spinal cord, although they do report an ipsilateral predominance for the PnC. Liang et al () present images that suggest an ipsilateral predominance in the PnO following tracer injections in the lumbar spinal cord.…”

“…Several previous retrograde tracing studies have demonstrated projections from the PRF to the spinal cord in the mouse and rat, ranging from embryonic to adult stages (mouse: Auclair et al, ; Vanderhorst and Ulfhake, ; Liang et al, ; rat: Basbaum and Fields, ; Satoh, ; Watkins et al, , 1981; Leong et al, ; Newman, ; Jones and Yang, ; Nudo and Masterton, ; Rye et al, ; Shen et al, ; Masson et al, ; Lakke, ; Auclair et al, ; Reiner et al, ; Huma et al, ). Only three of these studies combined unilateral tracer application with contralateral spinal cord hemisection to ensure unilateral tracing so that the laterality of projections could be unequivocally documented (Basbaum and Fields, ; Auclair et al, ; Vanderhorst and Ulfhake, ), as we have done here.…”

“…Only three of these studies combined unilateral tracer application with contralateral spinal cord hemisection to ensure unilateral tracing so that the laterality of projections could be unequivocally documented (Basbaum and Fields, ; Auclair et al, ; Vanderhorst and Ulfhake, ), as we have done here. In eight other studies, in the adult mouse or rat, unilateral applications were made but not combined with contralateral lesions to ensure unilateral tracing (Watkins et al, , 1981; Newman, ; Nudo and Masterton, ; Reiner et al, ; Liang et al, ; Huma et al, ). These studies will receive additional attention below.…”

Projections from the oral pontine reticular nucleus to the spinal cord of the mouse

“…Therefore, PnO must have a role in muscle relaxation during REM sleep. PnO has been shown to have spinal projections in many species [6][7][8][9][10][11] and its fiber termination in the spinal cord has also been reported in the rat [12,13] and cat [9,[14][15][16][17]. However, controversies in the projecting pattern also exist.…”