Neurons in the dorsal column white matter of the spinal cord: Complex neuropil in an unexpected location

Abstract

It is common to think of gray matter as the site of integration in neural circuits and white matter as the wires that connect different groups of neurons. The dorsal column (DC) white matter, for example, is the spinal cord axonal pathway through which a topographic map of the body is conveyed to the somatosensory cortex. We now describe a network of neurons located along the midline of the DCs. The neurons are present in several mammals, including primates and birds, and have a profuse dendritic arbor that expresses both the neuron-specific marker, microtubule-associated protein-2, and the neurokinin-1 receptor, a target of the neuropeptide, substance P. Electron microscopy and double immunostaining for synaptophysin and a marker of ␥-aminobutyric acid-ergic terminals documented a rich synaptic input to these neurons. Finally, injection of a ␥-aminobutyric acid type A receptor antagonist or of substance P into the cerebrospinal f luid of the rat spinal cord induced Fos expression and internalization of the neurokinin-1 receptor in these neurons, respectively, indicating that the DC neurons are under tonic inhibitory control and can respond to neurotransmitters that circulate in the cerebrospinal f luid.Although neuronal cell bodies are concentrated in the gray matter of the spinal cord and brain, there are several exceptions. Most notable are two neuronal groups in the white matter of the lateral columns of the spinal cord, the lateral cervical nucleus (1) and the lateral spinal nucleus (2). The former is located at the first and second cervical segments and is found in all species. The latter is prominent in the rat and is present at all levels of the spinal cord. Importantly, electrophysiological and anatomical studies have established that neurons within these two groups can be readily distinguished from neurons in the neighboring dorsal horn gray matter.To date, distinct neuronal cell groups have not been identified in the dorsal column (DC) white matter, which contains large-diameter primary afferent and second-order axons en route to the medulla (3). Here we provide evidence that the DCs, in fact, contain a population of neuronal cell bodies and a distinct neuropil. This finding was uncovered in the course of our studies of the organization of spinal cord neurons that express the neurokinin-1 (NK-1) receptor, which is targeted by the peptide substance P (SP). The cell bodies are concentrated near the midline of the DC white matter. In the present paper we establish that these cells are, in fact, neurons, that they receive a dense synaptic input and that they are under a profound tonic ␥-aminobutyric acid (GABA)-ergic inhibitory control.

Anatomical and functional characterization of neuropil in the gracile fasciculus

“…2d), suggesting a role in processing and/or transmitting information from the limbs. Some GF neurons express the NK1 receptor (Abbadie et al, 1999). In contrast to previous findings, only half (48 % Ϯ 2%, n ϭ 8) of all GF neuronal profiles were NK1 receptor-positive.…”

“…6). In contrast to a previous report (Abbadie et al, 1999), there were SP-positive synaptic boutons along the dendritic compartment of GF neurons of lentiform and fusiform cells (Fig. 6).…”

“…The projections of GF neurons have not been determined (Abbadie et al, 1999). No retrogradely labeled cells were found in the GF following CTB injection into the thalamus and gracile and cuneate nuclei, despite extensive labelling of spinothalamic/bulbothalamic and postsynaptic dorsal column neurons, respectively (data not shown).…”

“…4b). VGAT-positive boutons were abundant in the AST as described previously (Abbadie et al, 1999) and also in the CST (Fig. 4c).…”

“…Gray matter in the dorsolateral funiculus resembles an archipelago, with islands of neurons situated just ventral and lateral to the dorsal horn mainland. We know much about the structure and function of these neurons, but much less is clear about a midline diffuse nucleus in the gracile fasciculus (GF), on which there has been only one previous report (Abbadie et al, 1999;Fig. 1).…”