The organization of the neonatal rat's brainstem trigeminal complex and its role in the formation of central trigeminal patterns

The present study delimits the relationship of primary trigeminal afferents to their targets, the brainstem trigeminal nuclei of the neonatal rat. Previously, the brainstem trigeminal complex of the rat has been subdivided on the basis of either cytoarchitectonics or patterns of succinic dehydrogenase activity into the principal sensory nucleus and the three subnuclei of the spinal trigeminal nucleus, oralis, interpolaris, and caudalis. In this paper, we demonstrate that each of these subdivisions can also be identified by its pattern of primary trigeminal afferents. In addition, we demonstrate that the terminations of these afferents are distributed in a punctate fashion which correlates with vibrissae-related patterns of histochemical staining. Further, vibrissae removal in the neonatal rat at any age studied results in a corresponding deafferentation of both the principal sensory nucleus and all subnuclei of the spinal trigeminal nucleus. This same procedure has a graded, age-dependent effect on the vibrissae-related pattern of cytochrome oxidase staining in somatosensory cortex. On this basis, we conclude that vibrissae-related pattern formation in the central trigeminal system can be best understood in terms of a single "sensitive" period for the entire system. We hypothesize that this is the period during which an interaction normally occurs between primary trigeminal afferents and target neurons of the principal sensory nucleus.     

Long-term effects of neonatal axoplasmic transport attenuation on the organization of the rat's trigeminal system

The current study examined the long-term effects of infraorbital nerve (ION) axoplasmic transport attenuation with vinblastine on the organization of trigeminal (V) primary afferents and central vibrissae-related patterns. Retrograde tracing and single unit recording were used to evaluate the innervation of vibrissae follicles in adult (P > 60) rats that sustained application of vinblastine to the ION at birth. Single units recorded from vinblastine-treated animals yielded responses to deflection of a single vibrissa, and a significantly (P < 0.001) higher percentage of these cells (85.7%) showed rapidly adapting responses compared with normal rats (42.2%). Retrograde tracing revealed a qualitatively and normal distribution of V ganglion cells innervating A-row and E-row vibrissae follicles in vinblastine-treated rats. Transganglionic tracing with horseradish peroxidase (HRP) demonstrated a qualitatively and quantitatively normal somatotopic organization of vibrissae follicle input to V nucleus principalis (PrV) and V subnucleus interpolaris (SpI) in the vinblastine-treated animals. Despite the nearly normal mapping of V ganglion cell axons onto the vibrissae follicles and brainstem, staining for either cytochrome oxidase (CO) or parvalbumin failed to reveal vibrissae-related patterns in PrV, SpI, or the magnocellular portion of V subnucleus caudalis in these animals. Labelling of thalamocortical afferents with HRP and staining for CO also failed to reveal a cortical vibrissae-related pattern in the vinblastine-treated rats. The present results indicate that although transient attenuation of axoplasmic transport with vinblastine has limited effects on the peripheral and central projections of surviving V primary afferents, it permanently disrupts the normal development and maintenance of central vibrissae-related patterns. J. Comp. Neurol. 381:219-229, 1997. © 1997 Wiley-Liss, Inc.     

Development and plasticity in hamster trigeminal primary afferent projections

At birth (gestational day 16), the hamster infraorbital nerve projects to the appropriate portion of the brainstem, though the projection lacks adult-like internal organization (patchiness). Infraorbital nerve damage at this time does not produce appreciable transganglionic atrophy in the central projections of the infraorbital nerve, but it does result in a failure to develop normal infraorbital primary afferent patches. Such damage also produces a more widespread central projection of spared mandibular afferents into regions occupied by 'regenerate' infraorbital terminals (J. Comp. Neurol., 235 (1985) 129-143). In the present study, transganglionic transport techniques were again used to show that, by postnatal day 5 (gestational day 21), rostrocaudally continuous aggregates of horseradish peroxidase-labelled infraorbital terminals are visible throughout the trigeminal brainstem nuclear complex. This aggregation pattern is nearly adult-like and isomorphic with the distribution of the mystacial vibrissae on the face. A similar infraorbital lesion performed on postnatal day 5, however, markedly decreased the density of the adult central projection of the infraorbital nerve to subnuclei principalis, oralis, interpolaris, and the magnocellular laminae of caudalis. The projection to superficial laminae of caudalis and the cervical dorsal horn was maintained. A postnatal-day-5 infraorbital lesion also failed to produce a more widespread central projection from spared mandibular primary afferents. These data suggest a relationship between the postnatal maturity of trigeminal primary afferents and the response of damaged and undamaged trigeminal afferents to infraorbital nerve transection in hamster. The similarity in the central primary afferent response to lesions at equivalent gestational times (postnatal days 5 and 0, respectively) in hamster and rat, suggests that this plasticity gradient may be a general characteristic of mammalian trigeminal primary afferents.     

Cytoarchitectonic correlates of the vibrissae in the medullary trigeminal complex of the mouse

Cytoarchitectonic patterns in the medullary trigeminal complex of the mouse corresponding to mystacial vibrissae are described. These patterns are found within trigeminal sub-nuclei principalis, interpolaris and caudalis. The patterns are due to differential cell packing and are homeomorphic to the arrangement of the mystacial vibrissae on the face. The cytoarchitecture is similar, but complementary, to patterns of trigeminal afferents previously described using histochemical staining methods. Neonatal cautery of groups of vibrissae produces appropriate, specific and localized cytoarchitectural changes within all 3 trigeminal sub-nuclei.     

The barrelettes--architectonic vibrissal representations in the brainstem trigeminal complex of the mouse. I. Normal structural organization.

The organization of the brainstem trigeminal complex (BTC) of the mouse is described, with emphasis on the normal organization of the vibrissal representations. Thionin staining for Nissal substance was employed to reveal the cytoarchitecture. Cytochrome oxidase histochemistry was used to reveal the chemoarchitecture. Golgi impregnation methods, in combination with thionin staining, were used to examine the neuronal dendritic morphology within a defined cytoarchitectonic context. An in vitro horseradish peroxidase labelling method was used to study the distribution and morphology of primary trigeminal afferent terminals within the BTC. The BTC consists of four distinct subnuclei: principalis (nVp), oralis (nVo), interpolaris (nVi), and caudalis (nVc). The present study shows that these sub-nuclei can be distinguished from each other on the basis of several anatomical criteria, including the distribution and density of neuronal size classes, histochemical staining intensity, morphology and orientation of neuronal dendrites, and size and texture of primary afferent terminal arbors. Anatomical manifestation of vibrissal representations within the BTC can be described in nVp, nVi, and nVc, but not in nVo. Within the three subnuclei where they are found, anatomical vibrissal representations are composed to architectural subunits that form an overall pattern homeomorphic to the pattern of vibrissae on the face of the animal. Each sub-unit forms a cylindrical tube running in a rostrocaudal orientation within the BTC. These sub-units will be called barrelettes. Cytologically, each barrelette consists of cell-dense "sides," surrounding a practically cell-free "hollow." Individual sub-units are separated by narrow, cell-free "septa." Histochemically, each subunit is manifested as a discrete patch of positive-staining reaction products. Differential interference contrast optics shows that these patches correspond precisely to the barrelette hollows. Evidence is presented to show that the barrelettes are the functional units for the processing of vibrissal sensory information. Terminal arborizations of individual primary afferents seem to be confined to the hollow of single barrelettes. The majority of neurons that form the sides of a barrelette have bitufted dendritic arbors, which project predominantly into the barrelette hollow, although a minority of neurons, particularly in nVi and nVc, also extend part of their dendritic arbors into adjacent barrelette hollows. The barrelette hollows are thus the principal neuropil region in which primary afferents and their target neurons interact. Contacts are made mainly between en passant varicosities and terminal boutons on primary afferent collaterals and dendritic spines and shafts of second order neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of neonatal infraorbital lesions upon central trigeminal primary afferent projections in rat and hamster

Transganglionic and anterograde horseradish peroxidase transport was used to evaluate the central projections of undamaged trigeminal (V) nerve branches in adult rats and hamsters subjected to transection of the infraorbital nerve and to cauterization of the vibrissae follicles at birth. In rats, deafferented regions of the V brainstem nuclear complex did not receive abnormal projections from undamaged mandibular sensory afferents. Undamaged ophthalmic-maxillary fibers also failed to terminate heavily in the region deafferented by the neonatal infraorbital lesions. In the hamster, on the other hand, neonatal infraorbital nerve lesions were associated with statistically significant increases in mandibular terminal fields in the principalis, subnucleus interpolaris, and subnucleus caudalis. Tracing experiments were also carried out in neonatal rats and hamsters to determine whether the above-described differences in the response to infraorbital nerve damage reflected a difference in the maturity of the V primary afferent projections to the brainstem at the time of our neonatal lesions. In neonatal rats, the infraorbital and mandibular projections to the V brainstem nuclear complex were quite adultlike, both in their pattern and in the extent of their overlap, which was minimal. Overlap between mandibular and infraorbital terminal fields was also minimal in the newborn hamsters.     

2-DG uptake patterns related to single vibrissae during exploratory behaviors in the hamster trigeminal system

Stimulation of one or several whiskers activates discrete foci throughout the trigeminal (V) neuraxis. These foci contribute to patterns, corresponding to the patterns of vibrissae, that have been directly related to aggregates of cells and axon terminals in the “barrel” cortex. Here, we combine high-resolution, 2-deoxyglucose (2DG) mapping and cytochrome oxidase (CO) staining to determine whether the known pattern of V primary afferent projections is sufficient to deduce the functional activation of their targets during exploratory behavior. Four adult hamsters had all of their large mystacial vibrissae trimmed acutely, except for C3 on the left, and B2 and D4 on the right; in two others, the left C3 and right A1 and E4 whiskers were spared. After fasting overnight, 2DG was injected and the animals behaved freely in the dark for 45 minutes. The brainstem, thalamus, and cortices were sectioned, then processed for both CO staining and 2DG autoradiography. Image-processing microscopy was used to separate the autoradiographic silver grains from the histochemical staining. CO patches were patterned in a whiskerlike fashion in the full rostrocaudal extent of V nucleus principalis and in caudal portions of spinal V subnuclei interpolaris and caudalis, but absent in subnucleus oralis. 2DG silver grains were densest above those CO patches in the pattern corresponding to the active whiskers. There were no consistent 2DG foci in subnuclei oralis or rostral caudalais. In these same cases, prominent 2DG labeling was restricted to the appropriate barrels in the contralateral cortex. Only one case, however, displayed a clear and appropriate region of heightened 2DG uptake in contralateral ventroposteromedial thalamus (VPM) and the adjacent part of the reticular thalamic nucleus. Patterns of increased glucose utilization with single whisker stimulation are well matched to the CO patterns that mirror distributions of neurons associated with a vibrissa in the V brainstem complex, thalamus, and cortex. Single whiskers are represented by relatively homogeneous longitudinal columns of 2DG labeling in the V brainstem nuclei. The columns are not continuous through the axial extent of the V brainstem complex; rather, they occur separately within principalis, interpolaris, and caudalis. While whisker columns were consistently labeled in interpolaris and caudalis in all animals, the labeling was increasingly variable in principalis, barrel cortex, and VPM, respectively. This suggests that the behaving animal can and does significantly modulate activity in this major, synaptically secure pathway. © 1993 Wiley-Liss, Inc.     

Plasticity of Metabolic Whisker Maps in Somatosensory Brainstem and Thalamus of Mice with Neonatal Lesions of Whisker Follicles

We employed the autoradiographic deoxyglucose method to study metabolic whisker maps of the adult mouse somatosensory brainstem and thalamus after the neonatal removal of left whisker follicles C1, C2 and C3. Left whiskers B1–3 and D1–3 were deflected to metabolically activate the somatosensory pathway. Unoperated mice that were stimulated in the same fashion served as controls. Whisker stimulation resulted in an ipsilateral increase in metabolic activity in the three trigeminal brainstem structures in which the whiskers are represented topologically by segments of high cytochrome oxidase activity, i.e. subnucleus caudalis, subnucleus interpolaris and nucleus principalis. In the two subnuclei of mice with lesions and of controls, there was an increase in metabolic activity of the representations of the deflected whiskers, whereas the metabolic activity of representations A1–3 and E1–3 was low. Apart from these similarities, the metabolic activation of the representations originally representing whiskers C1–3 was remarkably greater in mice with lesions than in controls. This increase reached statistical significance in subnucleus caudalis and approached statistical significance in subnucleus interpolaris. In nucleus principalis the deprived territory was only partially activated and the degree of metabolic activation was less than in the subnuclei. In the thalamic ventrobasal complex of mice with lesions metabolic activity was unpatterned whereas two areas of metabolic activation were distinct in controls. Hence, the removal of whisker follicles in newborn mice resulted in the suppression of localized metabolic responses to whisker stimulation in the thalamus, whereas in the brainstem stimulus-related activity was prominent and the deprived territory became responsive to the stimulation of whisker follicles adjacent to the lesion. Apparently, the modification of the whisker representation at the first synapse of the pathway induces a diminution of localized responsivity in the thalamus.     

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

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.     

Cells of origin of the trigeminohypothalamic tract in the rat

Recent studies have demonstrated that a large number of spinal cord neurons convey somatosensory and visceral nociceptive information directly from cervical, lumbar, and sacral spinal cord segments to the hypothalamus. Because sensory information from head and orofacial structures is processed by all subnuclei of the trigeminal brainstem nuclear complex (TBNC) we hypothesized that all of them contain neurons that project directly to the hypothalamus. In the present study, we used the retrograde tracer Fluoro-Gold to examine this hypothesis. Fluoro-Gold injections that filled most of the hypothalamus on one side labeled approximately 1,000 neurons (best case = 1,048, mean = 718 ± 240) bilaterally (70% contralateral) within all trigeminal subnuclei and C1–2. Of these neurons, 86% were distributed caudal to the obex (22% in C2, 22% in C1, 23% in subnucleus caudalis, and 18% in the transition zone between subnuclei caudalis and interpolaris), and 14% rostral to the obex (6% in subnucleus interpolaris, 4% in subnucleus oralis, and 4% in subnucleus principalis). Caudal to the obex, most labeled neurons were found in laminae I–II and V and the paratrigeminal nucleus, and fewer neurons in laminae III–IV and X. The distribution of retrogradely labeled neurons in TBNC gray matter areas that receive monosynaptic input from trigeminal primary afferent fibers innervating extracranial orofacial structures (such as the cornea, nose, tongue, teeth, lips, vibrissae, and skin) and intracranial structures (such as the meninges and cerebral blood vessels) suggests that sensory and nociceptive information originating in these tissues could be transferred to the hypothalamus directly by this pathway. J. Comp. Neurol. 400:125–144, 1998. © 1998 Wiley-Liss, Inc.     

Trigeminal projections to the nucleus submedius of the thalamus in the rat.

Methods involving the anterograde and retrograde transport of wheat-germ agglutinin conjugated horseradish peroxidase and the retrograde transport of Fluoro-Gold were used in rats to examine the distribution within the spinal trigeminal nucleus of trigeminal neurons projecting to the nucleus submedius (Sm) of the thalamus, as well as the distribution of axon terminals within the Sm. Following injections into the trigeminal nucleus, axon terminals were seen in the dorsal part of the anterior Sm; the terminals occurred bilaterally but had an obvious contralateral dominance. To help determine the precise location of the Sm-petal neurons, the border between trigeminal subnuclei interpolaris and caudalis was examined by the use of immunohistochemical procedures for calcitonin gene-related peptide (CGRP). The Sm-petal neurons that were labeled retrogradely occurred only at the caudal interpolaris and rostral caudalis levels; the number of labeled neurons on the contralateral side was approximately six times that on the ipsilateral side. Most of these neurons were located in the ventral part of the caudal interpolaris and rostral caudalis and spinal trigeminal tract; in caudalis, the neurons were almost exclusively localized to its superficial layers. There were approximately three times more labeled neurons in interpolaris than in caudalis. In the experiments combined with immunohistochemistry for CGRP, many neurons (34%) were seen in proximity to CGRP-like immunopositive fibers. These results suggest that the Sm of the rat receives its orofacial afferent inputs from brainstem neurons that are localized to the caudal interpolaris and rostral caudalis. In view of previous studies that have implicated these three structures in somatosensory function, and in particular nociception, our data point to a role for this direct projection from interpolaris and caudalis to Sm in the central processing of pain.     

The corticotrigeminal projection in the cat. A study of the organization of cortical projections to the spinal trigeminal nucleus

The projection from the cerebral cortex to the spinal trigeminal nucleus has been studied light microscopically in adult cats. Both orthograde degeneration and orthograde intra-axonal labeling techniques have been applied. Our results indicate that the projection from the coronal gyrus (face area of primary somatosensory cortex) to the spinal trigeminal complex is somatotopically organized. In subnucleus caudalis this somatotopy is organized dorsoventrally and appears to match the somatotopic distribution of the divisional trigeminal afferents. Hence cortical fibers originating from the posterior coronal gyrus (upper representation) project ventrolaterally into caudalis where division I trigeminal afferents terminate. Likewise cortical fibers from the anterior coronal gyrus (jaw and tongue representation) terminate dorsomedially in caudalis to overlap with division III trigeminal afferents. In contrast, the distribution of corticofugal afferents to the rostral spinal trigeminal subnuclei (pars interpolaris and oralis) is organized mediolaterally. Therefore in these subnuclei the cortical projection does not appear to overlap the dorsoventral lamination of the divisional trigeminal afferents. In addition, our results suggest that the cortical projection to subnucleus caudalis includes fibers which terminate in the marginal zone (lamina I) and its extensions into the spinal trigeminal tract (the interstitial cells of Cajal). We have been unable to document a projection from the proreate gyrus to the spinal trigeminal complex.     

Barrelettes—architectonic vibrissal representations in the brainstem trigeminal complex of the mouse. II. Normal post-natal development

Vibrissal representations in the brainstem trigeminal complex (BTC) of rodents are manifested as architectural sub-units called barrelettes. The development of barrelettes was studied by using Nissl staining, cytochrome oxidase histochemistry, and Golgi-impregnation methods. On the day of birth (PND-1), barrelettes are manifested as longitudinal, histochemical cylinders in sub-nuclei principalis, interpolaris and caudalis of the BTC. One day later (PND-2), fully formed histochemical barrelette formations are seen in the three sub-nuclei. The development of cytoarchitectural barrelettes lags behind histochemical barrelettes by about two days. Between PND-2 and PND-3, longitudinal cytoarchitectonic cylinders begin to appear. By PND-3, BTC neurons segregate into five rows of barrelettes in the coronal plane. Segmentation of rows into individual barrelettes begins on PND-4, and complete cytoarchitectonic barrelette formations are seen by PND-5. Golgi-impregnation shows that on the day of birth, primary afferent terminals and dendritic arbors of second-order trigeminal neurons within the BTC are short and poorly ramified. Over the next five post-natal days, lengthening of these processes as well as elaboration into secondary and tertiary branches take place. Growth of these processes continues for two additional weeks, contributing to the increase in barrelette neuropils (hollows). As the neuropils expand, neuronal somata are pushed toward barrelette sides. Morphometric measurements show that there is a relatively constant rate of growth of barrelettes over the first three post-natal weeks. The growth rate of the barrelette formations is identical to that of BTC as a whole. Thus, at the time of birth, the volume of neural tissue in the brainstem allotted to vibrissae is fixed relative to that allotted to other sensory receptors. Several features of the early development of barrelettes are identified: (1) Chemoarchitectural barrelettes appear before cytoarchitectural barrelettes, suggesting that terminal arbors of primary trigeminal afferents are organized before their target neurons form barrelettes. (2) Early cytoarchitecture is manifested in the form of unsegmented rows, suggesting that rough, row-based topological maps are first formed, which are then fine-tuned into individual sub-units. Recent evidence shows that other vibrissal representations—thalamic barreloids and cortical barrels—also follow these “afferent-before-target” and “row-before-individual units” sequences of development. This gradual, afferent-dependent fine-tuning of topological organization is analogous to similar events during the early development of the visual system, and may be a general feature of developing sensory systems. In the visual system, sensory input plays an important role in fine-tuning centers in the brain; the mechanisms by which barrelettes are organized and fine-tuned are still unknown. 1993 Wiley-Liss, Inc.     

Organization of the spinal trigeminal nucleus in star‐nosed moles

Somatosensory inputs from the face project to multiple regions of the trigeminal nuclear complex in the brainstem. In mice and rats, three subdivisions contain visible representations of the mystacial vibrissae, the principal sensory nucleus, spinal trigeminal subnucleus interpolaris, and subnucleus caudalis. These regions are considered important for touch with high spatial acuity, active touch, and pain and temperature sensation, respectively. Like mice and rats, the star‐nosed mole (Condylura cristata) is a somatosensory specialist. Given the visible star pattern in preparations of the star‐nosed mole cortex and the principal sensory nucleus, we hypothesized there were star patterns in the spinal trigeminal nucleus subnuclei interpolaris and caudalis. In sections processed for cytochrome oxidase, we found star‐like segmentation consisting of lightly stained septa separating darkly stained patches in subnucleus interpolaris (juvenile tissue) and subnucleus caudalis (juvenile and adult tissue). Subnucleus caudalis represented the face in a three‐dimensional map, with the most anterior part of the face represented more rostrally than posterior parts of the face. Multiunit electrophysiological mapping was used to map the ipsilateral face. Ray‐specific receptive fields in adults matched the CO segmentation. The mean areas of multiunit receptive fields in subnucleus interpolaris and caudalis were larger than previously mapped receptive fields in the mole's principal sensory nucleus. The proportion of tissue devoted to each ray's representation differed between the subnucleus interpolaris and the principal sensory nucleus. Our finding that different trigeminal brainstem maps can exaggerate different parts of the face could provide new insights for the roles of these different somatosensory stations. J. Comp. Neurol. 522:3335–3350, 2014. © 2014 Wiley Periodicals, Inc.     

The organization of trigeminotectal and trigeminothalamic neurons in rodents: a double-labeling study with fluorescent dyes

Retrogradely transported fluorescent dyes (fast blue and diamidino-dihydrochloride yellow) were used to compare the distributions of trigeminofugal neurons that project to the superior colliculus and/or the thalamus in three rodent species. The objective was to determine what the projection and collateralization patterns of these trigeminofugal pathways are and whether they are similar among different species. In each anesthetized animal, one dye was injected into the superior colliculus and the other into the topographically congruent area of the thalamus. Counts of the numbers of yellow, blue, and double-labeled neurons were made throughout the trigeminal complex: principalis, pars oralis, pars interpolaris, and pars caudalis. Trigeminothalamic projections were similar in each of the rodent species studied. The densest concentration of retrogradely labeled neurons was in principalis, with substantially fewer neurons in pars interpolaris, and fewer still in pars oralis and pars caudalis. These neurons were generally small and tended to have round or fusiform somata. A common pattern was also noted among the three species for trigeminotectal neurons. Most trigeminotectal projections originated from neurons in pars interpolaris, somewhat fewer from pars oralis, and the fewest from principalis and pars caudalis. These neurons tended to be the largest in each subdivision and were often multipolar. Following paired injections of the tracers, double-labeled neurons were scattered throughout the sensory trigeminal complex and had morphologies characteristic of single-labeled trigeminotectal neurons. Although comparatively few double-labeled neurons were observed in any species, most of those seen were restricted to the ventrolateral portion of pars interpolaris, a position that corresponds to the representation of the vibrissae. These data indicate that, regardless of the rodent species, the vast majority of labeled trigeminal neurons project either to the superior colliculus or the thalamus, but not to both targets. This might be expected on the basis of the very different behavioral roles these structures play. On the other hand, a subpopulation of trigeminal neurons exists (mainly in pars interpolaris) that does project to both the superior colliculus and the thalamus, perhaps because both structures require some of the same somatosensory information to perform their behavioral functions.     

Maturation of the neuronal metabolic response to vibrissa stimulation in the developing whisker-to-barrel pathway of the mouse

We examined functional maturation in the mouse whisker-to-barrel pathway from P2 (P0 is the day of birth) to adulthood using the autoradiographic deoxyglucose (DG) method. After intraperitoneal DG injection, left whiskers C1–3 and E1 were stimulated. Sections were cut transversely through the brainstem, and coronally or tangentially through the parietal cortex. After autoradiography, the sections were stained for Nissl or for cytochrome oxidase (CO) activity. In subnuclei caudalis and interpolaris of the spinal trigeminal nucleus ipsilateral to stimulation, DG uptake evoked by the deflection of whiskers C1–3 was present at P2; in subnucleus oralis, nucleus principalis and the contralateral nucleus ventrobasalis of the thalamus, at P4; and in the contralateral barrel cortex, at P7. The first stimulus-dependent DG uptake appeared a few days after the appearance of whisker-related patterns seen in the CO- or Nissl-stained sections. In subnuclei caudalis and interpolaris, areas of stimulus-dependent DG uptake were initially larger than the CO segments representing the stimulated whiskers. Later, areas of stimulus-dependent DG uptake and CO segments matched well. DG uptake evoked by the stimulation of whisker E1 appeared 2–3 days later than that evoked by stimulation of whiskers C1–3. In nucleus principalis, one large area of stimulus-dependent DG uptake covered the representations of the caudal whiskers of all five rows - an observation made at all ages studied. In thalamus, stimulus-dependent DG uptake was found laterally in nucleus ventrobasalis. In barrel cortex, at P7, stimulus-dependent DG uptake was restricted to layers III and IV, but covered more barrels than whiskers stimulated. At P9, a second spot of high DG uptake was seen in deep layer V in register with that in layers III and IV. From P10 onwards, stimulus-dependent DG uptake stretched from layer II to layer VI, and in layer IV, in which it was highest, it was restricted to the barrels C1–3 and E1. In all stations, stimulus-dependent DG uptake decreased in magnitude after P10. While the onset of stimulus-dependent DG uptake is the result of the establishment of functional projections up to that station, the subsequent changes in size of the responding areas may well be due to the partial elimination of terminals, the maturation of local inhibitory circuits, and/or the development of cortical projections to the nuclei of termination and to the thalamic relay.     

Central projections of primary sensory neurons innervating different parts of the vibrissae follicles and intervibrissal skin on the mystacial pad of the rat.

The cell bodies and central projections of neurons innervating the vibrissae follicles and adjacent skin in the rat were investigated by retrograde and transganglionic transport of HRP. The cell bodies of neurons innervating the vibrissa follicle via the deep vibrissa nerve (DVN) were the largest, followed by those innervating the follicle via the superficial vibrissa nerve (SVN). The smallest cell bodies were those innervating the intervibrissal skin. The DVN neurons terminated centrally as an almost uninterrupted column through the trigeminal sensory nuclear complex. The DVN projections to nucleus caudalis and C1 dorsal horn were entirely restricted to laminae III, IV, and V. Besides the projections to lamina V, the DVN projections were strictly localized somatotopically at all levels replicating the peripheral organization of the vibrissae. The SVNs projected sparsely to midlevels of the main sensory nucleus but not to nuclei oralis and interpolaris. The main SVN projections appeared in laminae I-III of nucleus caudalis. In addition, a small projection to lamina V was observed. The projections to laminae II and III were organized mediolaterally in a similar way as the DVN projections; those to laminae I and V were less restricted. The intervibrissal skin neurons projected sparsely to the caudal main sensory nucleus and to the border between nuclei oralis and interpolaris. The projections to nucleus caudalis were restricted to laminae I-III and V and were organized in a similar way as the SVN projections.     

Organization of the nervous system after coagulation of the follicles of mystacial vibrissae in the newborn mouse: an example of neuronal plasticity

In the mouse the vibrissae and the common fur of the head are a good model of the so called neural plasticity. The characteristics of this model are: the pattern of implantation of the vibrissae at the periphery and that of the arrangement of barrels in the contralateral cortical projection area of vibrissae as well as that of the "barrelo?ds" in the subcortical vibrissal relays (somato sensory thalamus and trigeminal nuclear complex) are homeomorphic with one another. Each barrel and "barrelo?d" receives projections from one vibrissa. Moreover at the level of the cortex these projections are also in register with projections from ipsilateral vibrissae. Head fur hairs project to well defined but entirely distinct areas. Destruction of vibrissae follicles at birth beside preventing barrel and barrelo?d formation in the CNS, leads to several morphological changes: degeneration of the primary sensory neurons innervating vibrissae in the trigeminal ganglion, thus degeneration of their central axons and the corresponding terminals in the trigeminal vibrissal relays changes in the distribution of the activity of succinate dehydrogenase in the IVth layer of the cortical vibrissal area and in the corresponding subcortical relays, from the normal discrete (barrel hollow) pattern--corresponding to the clustered vibrissal afferents--to a continuous band, keeping a normal level of activity, excepted in the trigeminal vibrissal relays and a remarkable preservation of cortical thickness but a notable atrophy in the trigeminal vibrissal projection areas. Beside upsetting the anatomy vibrissae follicle destruction causes marked functional changes an outstanding take-over of the deafferented cortical vibrissal area (still identifiable from projections of vibrissae ipsilateral to it) by the head fur hairs this take over exist also in the subcortical vibrissal relays a change in the thalamo-cortical connections. Modifications in the organization of connections are initiated by the loss of the primary sensory neurons innervating vibrissae, in the trigeminal ganglion and results only from early lesions. In mice lesioned when adults the loss of primary sensory neurons is less important and functional take over by the common fur is not observed.     

Inputs from identified jaw-muscle spindle afferents to trigeminothalamic neurons in the rat: A double-labeling study using retrograde HRP and intracellular biotinamide

Projections from physiologically identified jaw-muscle spindle afferents onto trigeminothalamic neurons were studied in the rat. Trigeminothalamic neurons were identified by means of retrograde transport of horseradish peroxidase from the ventroposteromedial nucleus of the thalamus. Labeled neurons were found contralaterally in the supratrigeminal region (Vsup), the trigeminal principal sensory nucleus, the ventrolateral part of the trigeminal subnucleus oralis, the spinal trigeminal subnuclei interpolaris and caudalis, the reticular formation, and an area ventral to the trigeminal motor nucleus (Vmo) and medial to the trigeminal principal sensory nucleus (AVM). Jaw-muscle spindle afferents were physiologically identified by their increased firing during stretehing of the jaw muscles and intracellularly injected with biotinamide. Axon collaterals and boutons from jaw-muscle spindle afferents were found in Vmo; Vsup; the dorsomedial part of the trigeminal principal sensory nucleus (Vpdm); the dorsomedial part of the spinal trigeminal subnuclei oralis, interpolaris (Vidm) and caudalis; the parvicellular reticular formation (PCRt); and the mesencephalic trigeminal nucleus. Trigeminothalamic neurons in Vsup, Vpdm, Vidm, PCRt, and AVM were associated with axon collaterals and boutons from intracellularly stained jaw-muscle spindle afferents. Trigeminothalamic neurons in Vsup, Vpdm, Vidm, and PCRt were closely apposed by one to 14 intracellularly labeled boutons from jaw-muscle spindle afferents, suggesting a powerful input to some trigeminothalamic neurons. These data demonstrate that muscle length and velocity feedback from jaw-muscle spindle afferents is projected to the contralateral thalamus via multiple regions of the trigeminal system and implicates these pathways in the projection of trigeminal proprioceptive information to the cerebral cortex. © 1995 Wiley-Liss, Inc.     

Vibrissae representation in subcortical trigeminal centers of the neonatal rat

In the neonatal rat differential activity levels of the metabolic enzyme succinic dehydrogenase (SDH) reveal intricately detailed segmentation in the neuropil of the spinal and principal trigeminal nuclei of the brainstem and in the ventrobasal complex of the thalamus. The segmentation occurs in the portions of these nuclei that electrophysiological evidence has indicated to be related to the mystacial vibrissae and sinus hairs on the face of the rat. Indeed, the pattern of segmentation in each nucleus replicates the topographic distribution of the vibrissae and sinus hairs. Further, within the spinal trigeminal nucleus, there appear to be two distinct representations of the vibrissae, one in the subnucleus caudalis and a second in the subnucleus interpolaris. Examination of these patterns of segmentation indicates that the large mystacial vibrissae and sinus hairs on the face of the young rat are somatotopically represented three times within the trigeminal complex, as straight cylinders of neuropil, and once in the ventrobasal complex, as curved cylinders of neuropil. Neonatal vibrissae damage leads to an aberrant organization of the segmentation in the spinal trigeminal nucleus and the ventrobasal complex. In the spinal trigeminal nucleus, the SDH activity in areas associated with damaged vibrissae is of a lower than normal density, and patterns are indistinct. However, rows of clusters associated with the adjacent normal vibrissae are apparent and appear to be enlarged. In the ventrobasal complex, vibrissae damage results in bands of normal density SDH activity where rows of segmented clusters would normally be present. Comparison of these data to the cortical data in the previous paper (Killackey and Belford, '79) indicates that cortical and nuclear structures can have aspects of their development controlled by similar mechanisms.