Impact of chorda tympani nerve injury on cell survival, axon maintenance, and morphology of the chorda tympani nerve terminal field in the nucleus of the solitary tract

Abstract

Chorda tympani nerve transection (CTX) has been useful to study the relationship between nerve and taste buds in fungiform papillae. This work demonstrated that the morphological integrity of taste buds depends on their innervation. Considerable research focused on the effects of CTX on peripheral gustatory structures, but much less research has focused on the central effects. Here, we explored how CTX affects ganglion cell survival, maintenance of injured peripheral axons, and the chorda tympani nerve terminal field organization in the nucleus of the solitary tract (NTS). After CTX in adult rats, the chorda tympani nerve was labeled with biotinylated dextran amine at 3, 7, 14, 30, and 60 days post-CTX to allow visualization of the terminal field associated with peripheral processes. There was a significant and persistent reduction of the labeled chorda tympani nerve terminal field volume and density in the NTS following CTX. Compared with controls, the volume of the labeled terminal field was not altered at 3 or 7 days post-CTX; however, it was significantly reduced by 44% and by 63% at 30 and 60 days post-CTX, respectively. Changes in the density of labeled terminal field in the NTS paralleled the terminal field volume results. The dramatic decrease in labeled terminal field size post-CTX cannot be explained by a loss of geniculate ganglion neurons or degeneration of central axons. Instead, the function and/or maintenance of the peripheral axonal process appear to be affected. These new results have implications for long-term functional and behavioral alterations.

Microglia density decreases in the rat rostral nucleus of the solitary tract across development and increases in an age-dependent manner following denervation

“…This may explain why the robust microglia response to adult CTX across all rNTS zones, such as noted here, is accompanied by a preservation of the CT terminal fields despite temporary loss of afferent input (Reddaway et al, 2012). Microglia have been associated with peripheral nerve regeneration in other systems (DeFrancesco-Lisowitz et al, 2015) and the protective effect of microglia following adult CTX is implicated by studies which impact microglia function.…”

“…Minocycline has been used to inhibit microglial inflammatory response while leaving anti-inflammatory and protective functions intact (Kobayashi et al, 2013). As minocycline has no impact on the microglia response after adult mouse CTX (Bartel and Finger, 2013), this suggests that the microglia responding to adult CTX are already in an anti-inflammatory and protective state, preserving the CT terminal field (Reddaway et al, 2012) and possibly facilitating axonal regeneration and the recovery observed (St. John et al, 1995).…”

“…Tissue was further post-fixed for 24 hours in room temperature 4% paraformaldehyde, then horizontally sectioned at 40 μm on a vibrating microtome. Horizontal sections were used to facilitate comparisons to studies that have examined the CT terminal field following CTX (Sollars et al, 2006; Reddaway et al, 2012). …”

Regenerative Failure Following Rat Neonatal Chorda Tympani Transection is Associated with Geniculate Ganglion Cell Loss and Terminal Field Plasticity in the Nucleus of the Solitary Tract

“…Because it has been suggested that BDA transport to the brain becomes impaired after long-term neural injury (Reddaway et al, 2012) the long-lasting tracer DiI (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindocarbocyanine Perchlorate; D3911, Invitrogen) was applied in another group of animals at the time of CTX at P5 or P50 (n = 6/group). Since there is no long-term loss of CT volume after adult CTX (Reddaway et al, 2012), the rats labeled at P50 served as controls. Animals were anesthetized with Brevital ® (50 mg/kg, i.p.)…”

BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section

“…Thus, reinnervation occurs regularly in the normal taste system, even in the absence of nerve injury. This rich plasticity might explain why regeneration in the taste system after nerve injury is so robust (Cheal and Oakley, 1977; Reddaway et al, 2012; Shuler et al, 2004). When taste nerves are sectioned, taste buds are either completely lost or exhibit altered morphology (Fujimoto and Murray, 1970; Guagliardo and Hill, 2007; Oakley et al, 1990).…”