The rostromedial medulla participates in a large variety of sensory, motor, and autonomic functions. We asked whether individual bulbospinal neurons in this region have localized, target-specific terminal arbors or whether they collateralize broadly in the spinal cord. Collateralization was quantified along three spinal axes, rostrocaudal, left-right, and dorsoventral, by using double retrograde labeling. Fluorogold was applied to one target, and cholera toxin B chain (CTB) was applied to the second. We determined the prevalence of neurons that retrogradely label with both tracers in the constituent nuclei of the rostromedial medulla, the raphe nuclei, the gigantocellular reticular nucleus (Gi, bilaterally), the Gi pars alpha (GiA, bilaterally), and the midline medullary reticular formation. A large fraction of neurons in each of these nuclei had bulbospinal projections, ranging from > or =56% for the raphe nuclei to > or =14% for the Gi. For reasons discussed, these values are probably underestimates. Most of the neurons that projected to the lumbar spinal cord also projected to the cervical cord. Likewise, most neurons that projected to the ventral horn also had a collateral branch in the dorsal horn. However, relatively few had bilateral projections; most projected ipsilaterally or contralaterally. A considerable degree of collateralization was also seen among vestibulospinal neurons. The high level of collateralization of the descending projections of the rostromedial medulla suggests that neurons in this area ultimately act on peripheral target tissues or functions that are widely distributed in the body, or that they play a generalized modulatory role across functional modalities, rather than playing specific topographically delimited roles.
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.
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