Evidence for prenatal competition among the central arbors of trigeminal primary afferent neurons

Abstract

Previous studies have shown that damage to vibrissa follicles in newborn rats and mice does not alter the brainstem representations of the remaining vibrissa as demonstrated by staining for mitochondrial enzymes such as cytochrome oxidase (CO) succinic dehydrogenase. This study asked whether this lack of effect might be due to the fact that the trigeminal primary afferents in rodents are already quite well developed at birth. We assessed this possibility by using CO staining the evaluate patterns in the brainstems of pre- and postnatal rats. A vibrissa-related pattern began to emerge in trigeminal nucleus principalis and subnucleus interpolaris (Spl) by embryonic day (E-) 19 and appeared fully developed by the day of birth (P-0). We also made partial lesions of the vibrissa pad on E-15-20 and on P-0, killed pups on P-5-7, and measured the size of the CO-stained patches in Spl on both sides of the brainstem. The correspondence between CO patches and clusters of primary afferent terminal arbors was verified in some animals by combining transganglionic horseradish peroxidase tracing and CO staining. Vibrissa pad damage on E-15-18 resulted in significant (20.1-36.9%) increases in the average area of the remaining CO patches in Spl ipsilateral to the lesion. Vibrissa pad damage on E-19, E-20, and P-0 produced small (6.2-8.9%), but insignificant, increases in patch size in Spl ipsilateral to the lesion. We used anatomical and electrophysiological methods to determine whether our lesions altered the trigeminal innervation of surviving vibrissa follicles. We recorded single trigeminal ganglion cells from 12 rats that sustained vibrissa pad lesion on E-17. As in normal rats, all of the 49 vibrissa-sensitive ganglion cells isolated in the lesioned animals were responsive to deflection of one and only one vibrissa. We also dissected 11 deep vibrissal nerves from intact follicles in adult rats that sustained fetal vibrissa pad damage on E-17, and counted numbers of myelinated axons in 1 microns plastic sections. These data were compared with counts from corresponding follicles on the intact side of the face. The average number of myelinated axons innervating follicles in the damaged vibrissa pads was 196.8 +/- 27.9, and that for the corresponding contralateral nerves was 194.6 +/- 25.7. These data suggest that competitive interactions among the central arbors of trigeminal primary afferents in fetal life may influence the development of central vibrissa representations and, further, that lesion-induced central changes need not be correlated with alterations in the peripheral innervation of undamaged follicles.

Mapping somatosensory connectivity in adult mice using diffusion MRI tractography and super-resolution track density imaging

“…Additional 3D features of barrelette structures were observed including the rostro-caudal extent of tracks forming cylinder-shaped tubes (data not shown) (Belford and Killackey, 1979;Ma, 1991). We used cytochrome oxidase staining to detect enzyme activity in trigeminal afferent arbours and their postsynaptic target neurons, revealing the barrelette nuclei (Chiaia et al, 1992). In TDI, the barrelette connectivity map was seen in the coronal view in the ventro-lateral and interpolar regions as shown in cytochrome oxidase staining to demarcate the barrelettes in these regions (Li et al, 1994).…”

“…Cytochrome oxidase (CO) histochemistry was used to label the mitochondrial enzyme activity in trigeminal afferent arbours and their postsynaptic target neurons (Chiaia et al, 1992). CO was done using paraformaldehyde fixed tissue from additional C57Bl/6J mice aged P35 due to reduced CO activity after MRI processing.…”

“…Barreloid structural connectivity was empirically determined and the VPM barreloids were observed using 10 million tracks with track length 1-3mm ( Fig 3A,B and Supplementary Table ST1). TDI mapping results for the thalamus were compared with barreloid topography identified using cytochrome oxidase stained sections, which labels the mitochondrial enzyme activity in trigeminal afferent arbours and their postsynaptic target neurons (Chiaia et al, 1992), in an equivalent brain region for young mice (age P3; Fig 3C,D). However, our results suggest that the barreloids were difficult to detect using histology in the adult thalamus, consistent with previous reports (Fig 3E,F); this is believed to be due to increased inter-barreloid connections in mature rodents (Zantua et al, 1996).…”

InDRG11Knock-Out Mice, Trigeminal Cell Death Is Extensive and Does Not Account for Failed Brainstem Patterning

“…Only NMDA NR1 (Li et al, 1994;Iwasato et al, 1997), DRG11, and Hoxa2 are necessary for barrel-like patterning in the PrV. Insofar as PrV is the V nucleus that is required for thalamic and cortical patterning (Killackey and Fleming, 1985) and because PrV is the first nucleus in the pathway to develop barrel-like patterns (Bates and Killackey, 1985;Chiaia et al, 1992), PrV may be the true pattern maker in this system. DRG11 is the first transcription factor shown to be necessary for barrel-like development (Ding et al, 2003), functioning selectively in the PrV, with no patterning function in the spinal V nucleus.…”

L-Type Calcium Channel-Mediated Plateau Potentials in Barrelette Cells During Structural Plasticity

“…These patterns are first established in the brain stem trigeminal complex where they are called "barrelettes," and sequentially in the ventroposteromedial nucleus (VPM) of the dorsal thalamus ("barreloids") and in layer IV of the primary somatosensory cortex ("barrels") (for reviews, see Erzurumlu and Kind 2001;Killackey et al 1995;O'Leary et al 1994;Woolsey 1990). In the rat, barrelette patterns in the brain stem trigeminal nuclei develop before birth (Chiaia et al 1992) and are dependent on the infraorbital (IO) nerve, which innervates the whiskers and sinus hairs. Trigeminothalamic projection cells (barrelette neurons) of the principal sensory nucleus (PrV) convey this pattern to the VPM, and VPM neurons in turn relay the patterns to the barrel cortex (Erzurumlu and Jhaveri 1990;Erzurumlu and Kind 2001;Killackey and Fleming 1985).…”