Direct projections from the ventrolateral medulla oblongata to the limbic forebrain: Anterograde and retrograde tract‐tracing studies in the rat

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Abstract
Neurons in the ventrolateral medulla oblongata, a brain region implicated in central vasomotor regulation, have previously been reported to project to some forebrain limbic structures. The aim of the present study was (1) to describe the termination pattern of ventral medullary afferents in forebrain limbic areas using anterograde tract tracing, and (2) to determine the location and some morphological characteristics of the projection neurons using retrograde tract tracing from selected forebrain sites.Following ionophoretic microinjections of the anterograde tract tracer Phaseolus vulgaris leucoagglutinin into the rostral ventrolateral medulla, labelled afferents were observed in the hippocampus, entorhinal and retrosplenial cortices, dorsal septum, nucleus accumbens, and the medial prefrontal cortex. Anterogradely labelled axons, ascending from the caudal ventrolateral medulla, could be traced only to the rostral aspects of the investigated forebrain limbic structures. Here, the main target of the ascending projection was in the ventral septum. However, labelled terminals were also present in the nucleus accumbens, the dorsolateral septum, and in the infralimbic cortex. The density of the ventrolateral medullary projections into all examined forebrain areas was low.The location of the cells in the ventral medulla oblongata which give rise to direct forebrain projections was examined using retrograde tract tracing with wheat germ agglutinin conjugated horseradish peroxidase (WGA‐HRP). Following WGA‐HRP injections into the septo‐accumbens region, retrogradely labelled cells were present in both the rostral and caudal ventrolateral medulla. When the tract tracer injection was restricted to the ventral region of the septal complex, the labelled cells were concentrated in the caudal aspects of the ventrolateral medulla (and the nucleus of the solitary tract). Following tracer injections into the anterior cingulate cortex or the hippocampus or the entorhinal cortex, retrogradely labelled cells in the medulla oblongata were predominantly in the rostral ventrolateral medulla.As a first attempt to reveal the chemical nature of the projection cells, the contribution of tyrosine hydroxylase‐immunoreactive cells to the innervation of the septo‐accumbens area was also investigated: tyrosine hydroxylase‐immunoreactive cells of both the caudal ventrolateral medulla and the nucleus of the solitary tract were found to contribute to the innervation of the septo‐accumbens area.The distribution of retrogradely labelled cells as well as the termination pattern of the anterogradely labelled terminals indicated that the innervation of the various forebrain limbic areas arises from cells, diffusely distributed in the rostral and/or the caudal ventrolateral medulla oblongata. Considering the important role of the ventrolateral medulla oblongata in autonomic coordination, it is proposed that direct projections from the ventral medulla oblongata to limbic forebrain structures might contribute to the coordination of behavioural states and cardiovascular performance. © Wiley‐Liss, Inc.

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