Neuroglial modulation in peripheral sensory systems.

Glia are increasingly appreciated as active participants in central neural processing via calcium waves, electrical coupling, and even synaptic-like release of "neuro"-transmitters. In some sensory organs (e.g., retina, olfactory bulb), glia have been shown to interact with neurons in the same manner, although their role in perception has yet to be elucidated. In the organ of Corti, synapses occur between supporting cells and neurons. In one sensory organ, the Pacinian corpuscle (fine touch), glia have been shown to play just as important a role in sensory transduction as they do in neural processing in the brain, and the functional role is quite clear; the modified Schwann cells of the capsule are responsible for the rapid adaptation process of the PCs, integral to its function as a vibration detector. This complex glial/neuronal relationship may be a recent evolutionary phenomenon and may account for much of the relative sophistication of vertebrate nervous systems.

GABAergic/glutamatergic-glial/neuronal interaction contributes to rapid adaptation in pacinian corpuscles.

Pacinian corpuscles (PCs) are tactile receptors composed of a nerve ending (neurite) that is encapsulated by layers of lamellar cells. PCs are classified as primary mechanoreceptors because there is no synapse between the transductive membrane and the site of action-potential generation. These touch receptors respond in a rapidly adapting manner to sustained pressure (indentation or displacement), which until now was believed to be attributable solely to the mechanical properties of the capsule. However, evidence of positive immunoreactivity for GABA receptors on the neurite, as well as evidence for gene expression of synaptobrevin in the lamellar cells led to the hypothesis that GABAergic inhibition originating from the lamellar cells is involved in the rapid adaptation process of PCs. Electrophysiological data from isolated PCs demonstrates that, in the presence of either gabazine or picrotoxin (GABA receptor antagonists), many action potentials appear during the static portion of a sustained indentation stimulus (similar to slowly adapting receptors) and that these "static" spikes completely disappear in the presence of GABA. It was consequently hypothesized that glutamate, released by either the neurite itself or the lamellar cells, caused these action potentials. Indeed, the glutamate receptor blocker kynurenate either decreased or totally eliminated the static spikes. Together, these results suggest that GABA, emanating from the modified Schwann cells of the capsule, inhibits glutamatergic excitation during the static portion of sustained pressure, thus forming a "mechanochemical," rather than purely mechanical, rapid adaptation response. This glial-neuronal interaction is a completely novel finding for the PC.

Mesenteric and tactile Pacinian corpuscles are anatomically and physiologically comparable.

Pacinian corpuscles (PCs) in cat mesentery have been studied extensively to help determine the structural and functional bases of tactile mechanotransduction. Although we, like many other investigators, have found that the mesenteric receptors are anatomically very similar to those found in mammalian skin, few physiological characteristics of the mesenteric PCs and those of the skin have been compared. Action-potential rate-amplitude and frequency characteristics (10 Hz-1 KHz), as well as interval (IH) and peri-stimulus-time (PSTH) histograms in response to sinusoidal displacements were obtained from nerve fibers innervating mesenteric PCs and from PC fibers innervating cat glabrous skin. The intensity characteristics obtained on both preparations showed similar response profiles, including equal slopes for low stimulus intensities (approximately 10, with impulse ratios/20 dB displacement) and one and two impulse/cycle entrainment. The frequency characteristics of both groups were U-shaped with similar low-frequency slopes (-12.5 dB/octave) and bandwidths (Q(3dB) = 1.4). The best frequency for both the tactile PCs' and mesenteric PCs was 250 Hz, which is in the expected range. The IHs showed entrainment and the PSTHs showed neither transient responses nor adaptation to steady-state sinusoidal stimuli. The functional similarity between mesenteric PCs' nerve responses and those of tactile PC afferents, as well as the receptors' anatomical similarity, lead us to suggest that the mesenteric PC can act as a model for those in the skin. Furthermore, since the frequency characteristics of the two PC types are similar, it is concluded that the skin, while attenuating stimulus intensity, does not impart temporal filtering of vibratory stimuli.

Localization of Merkel cells in the monkey skin: an anatomical model.

The Merkel cell-neurite complex is considered to be one class of mechanoreceptors in the skin. Merkel cells are innervated by slowly adapting type I (SAI) tactile nerve fibers. In this paper, the detailed distribution of Merkel cells is studied by immunohistochemical labeling of the monkey (Macaca fascicularis) digital glabrous skin. Specific morphometric variables (density of intermediate epidermal ridges and Merkel cells, distance between skin surface and ridge tips and bases, maximum and average cell counts per ridge, distance between cells and ridges) were measured by a combination of light/fluorescence microscopy and computer-image analysis. The morphometric results were similar for each digit of the monkey's hand. Next, the anatomical data were used to form a three-dimensional reconstruction of the Merkel-cell distribution in the fingertip skin. A patch of the distal-pad surface was then computationally flattened to obtain the two-dimensional distribution of Merkel cells. Based on previous anatomical and physiological data, SAI fibers were simulated to innervate clusters of Merkel cells in the distal-pad surface. On average, 28 cells were innervated by a single fiber. The resulting anatomical model may be used to estimate the population response of SAI fibers by incorporating spike generation.

Possible glutaminergic interaction between the capsule and neurite of Pacinian corpuscles.

The role of the capsule encasing the Pacinian corpuscle's (PC's) neurite, where mechanotransduction occurs, may be more than mechanical. The inner core of the PC's capsule consists of lamellar cells that are of Schwann-cell origin. Previously, we found both voltage-gated Na+ and K+ channels in these inner-core lamellae. Research on astrocytes and Schwann cells shows bidirectional signaling between glia and neurons, a major component of which is glutamate. Furthermore, Merkel cells show positive immunoreactivity for glutamate receptor mGluR5, and the glutamate-receptor antagonist kynurenate greatly decreases the static activity of the slowly adapting neurons of Merkel cell-neurite complexes. To investigate the possibility of glutaminergic interaction in PCs, we applied antibodies to glutamate, glutamate receptors, glutamate transporters, and SNARE proteins to cat mesenteric PC sections. Positive labeling was seen in the inner-core lamellae, at inter-lamellar connections, where the lamellae contact the membrane of the neurite and at the lamellar tips. The presence of these proteins on the lamellae and neurite membranes, demonstrated both with immunofluorescent light microscopy as well as immunogold electron microscopy, suggests a chemical, possibly bidirectional, interaction between the lamellar cells and the neurite. Thus, the capsule of the PC, apart from having a mechanical filtering function, may also provide an environment for lamellar-neurite interaction, perhaps acting as a neuro-modulator of the initiation, and/or continuation, of the mechanical-electrical transduction process. At the very least, the presence of the aforementioned proteins suggest some sort of "synaptic-like" activity in these mechanoreceptors, which up until now has not been considered possible.