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PubMed1990

The perinatal reorganization of the innervation of skeletal muscle in mammals.

(1) The perinatal reorganization of muscle innervation is executed in a setting established by the earlier embryonic developmental processes. Prominent among these is the generation of a stereotyped set of skeletal muscles, each innervated in an orderly fashion from an appropriate pool of spinal motoneurons. The muscles contain functionally specialized types of fibers which differentiate in patterns characteristic for each muscle even without innervation. (2) Cholinergic motoneurons are required for functional innervation of skeletal muscles. In addition the muscle fibers must be in a receptive state. Denervation or paralysis recreates the receptive state. Chemically the receptive state is not well defined. It is associated with an immature distribution of AChRs and NCAM. (3) Nmjs are located in an orderly fashion on muscle fibers. Their normal distribution can be disrupted by paralysis during development. When junctions are first formed the nerve terminal induces local aggregation, stabilization and mature ionophore kinetics of the AChRs, as well as appearance of junctional specific AChE. Some of the effects require muscle activity. Terminal-derived substances like agrin and CGRP may normally contribute to these processes, as may other not yet identified agents. (4) Numerically, motoneuronal pools are regulated according to the available target. At the same time, the generation of secondary myotubes requires innervation by active motoneurons, and may also be quantitatively regulated by the number of innervating motoneurons. The generation of the primary generation of myotubes is independent of innervation. (5) Soon after the muscle fiber is first innervated additional terminals from other axons form junctions at the same site. The extent of polyneuronal innervation differs between muscles and between fiber types in the same muscle. Following a delay of several days after birth the individual terminals increase their contact area by arborization. The postsynaptic differentiation with redistribution of AChR, AChE and formation of subsynaptic folds is initiated. The complete maturation of the endplate requires several weeks. (6) Around birth or a few days later processes which eliminate redundant terminals are initiated. The rate of elimination appears to be aimed at nearly synchronous completion of the process in muscles with related functions. (7) There are two types of processes involved in the elimination of supernumerary terminals. The one gives rise to a competitive interaction between terminals innervating the same muscle fiber. The second is related to the reduction in the number of terminals which a motoneuron can maintain in the muscle. The two normally act in concert to determine the mature pattern of innervation of a muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2007

Immunohistochemical analysis of wrist ligament innervation in relation to their structural composition.

PURPOSE: To analyze ligament innervation and the structural composition of wrist ligaments to investigate the potential differences in sensory and biomechanical functions. METHODS: The ligaments analyzed were the dorsal radiocarpal, dorsal intercarpal, scaphotriquetral, dorsal scapholunate interosseous, scaphotrapeziotrapezoid, radioscaphoid, scaphocapitate, radioscaphocapitate, long radiolunate, short radiolunate, ulnolunate, palmar lunotriquetral interosseous, triquetrocapitate, and triquetrohamate ligaments. The ligaments were harvested from 5 cadaveric, fresh-frozen specimens. By using the immunohistochemical markers p75, Protein Gene Product 9.5, and S-100 protein, the mechanoreceptors and nerve fibers could be identified. RESULTS: The innervation pattern in the ligaments was found to vary distinctly, with a pronounced innervation in the dorsal wrist ligaments (dorsal radiocarpal, dorsal intercarpal, scaphotriquetral, dorsal scapholunate interosseous), an intermediate innervation in the volar triquetral ligaments (palmar lunotriquetral interosseous, triquetrocapitate, triquetrohamate), and only limited/occasional innervation in the remaining volar wrist ligaments. The innervation pattern also was reflected in the structural differences between the ligaments. When present, mechanoreceptors and nerve fibers were consistently found in the loose connective tissue in the outer region (epifascicular region) of the ligament. Hence, ligaments with abundant innervation had a large epifascicular region, as compared with the ligaments with limited innervation, which consisted mostly of densely packed collagen fibers. CONCLUSIONS: The results of our study suggest that wrist ligaments vary with regard to sensory and biomechanical functions. Rather, based on the differences found in structural composition and innervation, wrist ligaments are regarded as either mechanically important ligaments or sensory important ligaments. The mechanically important ligaments are ligaments with densely packed collagen bundles and limited innervation. They are located primarily in the radial, force-bearing column of the wrist. The sensory important ligaments, by contrast, are richly innervated although less dense in connective tissue composition and are related to the triquetrum. The triquetrum and its ligamentous attachments are regarded as key elements in the generation of the proprioceptive information necessary for adequate neuromuscular wrist stabilization.

Aged↗
PubMed2003

Re-establishment of neurochemical coding of preganglionic neurons innervating transplanted targets.

We investigated the effect on neurochemical phenotype of changing the targets innervated by sympathetic preganglionic neurons. In neonatal rats, the adrenal gland was transplanted into the neck, to replace the postganglionic neurons of the superior cervical ganglion. Transplanted adrenal glands survived, and contained noradrenergic and adrenergic chromaffin cells, and adrenal ganglion cells. Retrograde tracing from the transplants showed that they were innervated by preganglionic neurons that would normally have supplied postganglionic neurons of the superior cervical ganglion. The neurochemical phenotypes of preganglionic axons innervating transplanted chromaffin cells were compared with those innervating the normal adrenal medulla or superior cervical ganglion neurons. As in the normal adrenal gland, preganglionic nerve fibres apposing transplanted chromaffin cells were cholinergic. The peptide and calcium-binding protein content of preganglionic fibres was similar in normal and transplanted adrenal glands. In both cases, cholinergic fibres immunoreactive for enkephalin targeted adrenergic chromaffin cells, whilst cholinergic fibres with co-localised calretinin-immunoreactivity innervated noradrenergic chromaffin cells and adrenal ganglion cells. In contrast to the innervation of normal adrenal glands, these axons lacked immunoreactivity to nitric oxide synthase. In a set of control experiments, the superior cervical ganglion was subjected to preganglionic denervation in rat pups the same age as those that received adrenal transplants, and the ganglion was allowed to be re-innervated over the same time course as the adrenal transplants were studied. When the superior cervical ganglion was re-innervated by preganglionic nerve fibres, we observed that all aspects of chemical coding were restored, including cholinergic markers, nitric oxide synthase, enkephalin, calcitonin gene-related peptide and calcium binding proteins in predicted combinations, although the density of nerve fibres was always lower in re-innervated ganglia. These data show that the neurochemical phenotypes expressed by preganglionic neurons re-innervating adrenal chromaffin cells are selective and similar to those seen in the normal adrenal gland. Two explanations are advanced: either that contact of preganglionic axons with novel target cells has induced a switch in their neurochemical phenotypes, or that there has been target-selective reinnervation by pre-existing fibres of appropriate phenotype. Regardless of which of these alternatives is correct, the restoration of normal preganglionic codes to the superior cervical ganglion following denervation supports the idea that the target tissue influences the neurochemistry of innervating preganglionic neurons.

Adrenal Glands↗
PubMed1977

Re-innervation of guinea-pig superior cervical ganglion cells by preganglionic fibres arising from different levels of the spinal cord.

1. The ability of preganglionic axons to re-establish their normal pattern of synaptic connexions with superior cervical ganglion cells has been studied after section of the cervical sympathetic trunk.2. In vivo stimulation of the last cervical (C8) and the first seven thoracic ventral roots (T1-T7) 3-4 months after section of the trunk produced end-organ responses similar to those observed in normal animals.3. The pattern of innervation of individual neurones, determined by intracellular recording of synaptic potentials 4-9 months after cutting the sympathetic trunk, was also similar to that observed in normal neurones. Both normal and re-innervated ganglion cells were contacted by pre-ganglionic axons arising from C8 to T7, and each neurone was usually innervated by a contiguous subset of these segments.4. Re-innervated neurones, as normal cells, were typically dominated by the innervation from a particular spinal cord segment, with the adjacent segments contributing a synaptic influence that decreased as a function of distance from the dominant segment. This was true whether the amplitude of the post-synaptic potential, or the estimated number of contributing axons, was used as the criterion of segmental dominance.5. Re-innervated neurones, however, showed some abnormalities. The average number of ventral roots contributing innervation to each neurone was reduced from 4.1 to 3.0, and discontinuities in the sequence of innervating segments were more frequent than in normal neurones. Moreover, fewer preganglionic axons contacted each neurone after regeneration.6. A further difference between normal and re-innervated neurones during the period covered by these experiments was that axons from the more caudal spinal cord segments were less successful in re-establishing contacts with ganglion cells than those from the rostral segments. The more caudal the position of the preganglionic neurones, the more pronounced was this relative deficiency.7. Although anomalies of ganglion cell innervation were apparent, the basis for the restoration of normal functional effects appears to be the re-establishment of a pattern of innervation of individual neurones similar to that observed in normal ganglia.

Action Potentials↗
PubMed1980

The elimination of redundant preganglionic innervation to hamster sympathetic ganglion cells in early post-natal life.

The superior cervical ganglion of adult and neonated hamsters has been studied with intracellular recording. 1. Neurones in adult hamster ganglia are innervated by an average of 6-7 preganglionic axons. During the first week of post-natal life, however, these cells are innervated by at least eleven to twelve axons. Ganglion cells in animals 2-3 weeks old are innervated to an intermediate degree, indicating that these neurones lose a substantial portion of their initial synaptic contacts during the first weeks after birth. 2. The over-all innervation of the superior cervical ganglion in adult hamsters arises from thoracic segments T1-T5; no additional segments contribute significantly to the innervation of neonatal ganglia. 3. The average number of segments innervating each adult ganglion cell is 2 . 8 compared to 3 . 7 segments innervating neonatal neurones. Throughout post-natal development the innervation of individual neurones arises from a contiguous subset of the spinal segments that innervate the ganglion as a whole. 4. We conclude that the elimination of redundant innervatin in early life is not limited to those nerve and muscle cells contacted by a sigle axon in maturity, but also occurs in sympathetic ganglia where adult neurones remain multiply innervated. Moreover, the loss of some synaptic contacts during development refines the selective innervation of individual neurones.

Animals↗
PubMed1981

Re-innervation of ganglia transplanted to the neck from different levels of the guinea-pig sympathetic chain.

Thoracic and lumbar sympathetic ganglia from donor guinea-pigs were transplanted to the bed of an excised superior cervical ganglion in host animals. Homotopic transplants of superior cervical ganglia served as controls. In this way the same set of preganglionic axons (the cervical sympathetic trunk) was confronted with ganglia from different levels of the sympathetic chain. Re-innervation of the transplants was studied after 3-5 months. 1. Neurones in ganglia transplanted from different levels of the sympathetic chain were re-innervated to about the same over-all degree by the preganglionic axons of the host's cervical sympathetic trunk. Thus, the mean amplitude of post-synaptic potentials, the estimated number of innervating axons, and the number of spinal segments providing innervation to each neurone were similar in transplanted thoracic, lumbar and superior cervical ganglion cells. 2. Neurones in transplanted mid-thoracic ganglia, however, were re-innervated more frequently, and more strongly, by axons arising from more caudal thoracic segments than neurones in transplanted superior cervical ganglia. Stimulation of axons arising from the fourth thoracic spinal segment (T4), for example, elicited post-synaptic potentials that on average were twice as large in transplanted fifth thoracic ganglion cells as in transplanted superior cervical ganglion cells; conversely, axons arising from T1 re-innervated neurones in the superior cervical ganglion about 2-3 times more effectively than fifth thoracic ganglion cells. This difference in the re-innervation of the fifth thoracic and the superior cervical ganglion is in the same direction as (although less pronounced than) the normal difference in the segmental innervation of these ganglia. 3. Transplanted lumbar ganglia were also re-innervated more effectively by relatively caudal segments compared to re-innervated cervical ganglia, but this difference was no greater than that observed for transplanted thoracic ganglia. 4. We conclude that preganglionic axons can distinguish (or be distinguished by) ganglia derived from different levels of the sympathetic chain. Our findings are consistent with the view that ganglion cells have some permanent property that biases the innervation they receive.

Animals↗
PubMed1990

Development of the adrenergic innervation in the myocardium and coronary arteries of the dog.

The development of the adrenergic cardiac innervation was studied in premature dog fetuses, puppies and adult dogs by means of the formalin-induced fluorescence technique. A point-counting technique was used to evaluate the density of innervation. Two types of fluorescent profiles can be observed in the heart during development: (1) sprouting axons, and (2) beaded terminals. The axonal fluorescence disappears in adult neurons. A different morphology and a different time course of development enable to study separately the innervation of the myocardium (cardiomotor innervation) and that of the vessels (vasomotor innervation). The late prenatal innervation is very poor (0.1 hit). The first but very scant cardiomotor terminals appear in this period. A mature cardiomotor innervation is found in 4-month-old puppies [1.5 +/- 0.3 (SD) hits]. The vasomotor innervation is shifted to the right. The development of beaded vascular terminals begins and matures 1-2 weeks later. The growing fluorescent axons reveal that the myocardium is supplied by axons of the cardiac plexus and of the perivascular nerves; the vascular wall, on the other hand, is supplied by the perivascular nerves only. The developmental, spatial and morphological differences in innervation suggest that two different types of neurons exist in the sympathetic ganglia: (1) neurons innervating the vessels (coronaromotor neurons), and (2) neurons innervating the myocardium (cardiomotor neurons).

Adrenergic Fibers↗
PubMed1983

Rat extraocular muscle. 1. Three dimensional cytoarchitecture, component fibre populations and innervation.

Rat superior oblique extraocular muscle was examined in serial sections by light and electron microscopy. By such analysis, it was possible to discriminate single versus multiply innervated fibres, characteristics of the internal structure of fibres, and topographical distribution of the respective fibre populations within the muscle. The superior oblique muscle was observed to consist of two distinguishable muscle portions; one portion originated proximally and the other muscle portion originated distally after passing through the trochlea tendon. Seven morphologically distinct fibre populations were discernible. Four populations, three singly innervated fibre populations and one multiply innervated fibre population, were localised in the global region; these differed in terms of diameter, mitochondrial richness, development of the sarcoplasmic reticulum and myofibrillar size. The orbital surface layer contained two singly innervated and one multiply innervated populations; all of these exhibited systematic morphological variability. The multiply innervated fibres displayed multiple, relatively superficial, neuromuscular junctions along their length, as well as end plate-like junctions which were apparently confined to the region of the singly innervated fibre innervation band, thus suggesting polyneuronal innervation. In the latter region, the multiply innervated fibres displayed morphological features characteristic of "twitch' fibres; away from this region these cells appeared to have morphological features typical of "tonic' fibres. In contrast, the global multiply innervated fibres were constant diameter and form along their length, and displayed only relatively superficial neuromuscular junctions.

Animals↗
PubMed1996

Functional motor innervation of brachial plexus roots. An intraoperative electrophysiological study.

OBJECTIVE: To study the functional motor innervation of C5-T1 nerve roots of the brachial plexus electrophysiologically. PATIENTS AND METHODS: The electrophysiological properties of normal brachial plexus roots and their functional motor innervation were examined in 15 patients with brachial plexus injuries, while the contralateral healthy side C7 root transfer was operated on. Different nerve roots of the brachial plexus were stimulated and maximum amplitudes were recorded in the following 12 muscles: deltoid, biceps, infraspinatus, brachiaradialis, flexor carpi radialis, triceps, extensor digitorum communis, latissimus dorsi, flexor digitorum profundus, abductor brevis, abductor digiti minimi and flexor carpi ulnaris. RESULTS: Functional motor innervation of brachial plexus roots showed the following results: a. C5 mainly forms the axillary nerve to innervate deltoid muscle; b. C6 mainly constructs the musculocutaneous nerve to innervate biceps muscle; c. C7 mainly forms the radial nerve to innervate triceps muscle; d. C8 mainly forms the median nerve to innervate the flexor digitorum muscle; e. T1 mainly forms the ulnar nerve to innervate the intrinsic muscles of the hand. CONCLUSIONS: The brachial plexus is functionally divided into three groups: C5, 6 innervate shoulder and elbow; C8T1 innervate the hand; and C7 innervates shoulder, elbow, wrist and hand. Theoretically, any division of the nerve root alone may not cause damage to limb function.

Adolescent↗
PubMed1998

Innervation of single fungiform taste buds during development in rat.

To determine whether the innervation of taste buds changes during postnatal development, the number of geniculate ganglion cells that innervated single fungiform taste buds were quantified in the tip- and midregions of the tongue of adult and developing rats. There was substantial variation in both the size of individual taste buds and number of geniculate ganglion cells that innervated them. Importantly, taste bud morphology and innervation were highly related. Namely, the number of labeled geniculate ganglion cells that innervated a taste bud was highly correlated with the size of the taste bud (r = 0.91, P < .0003): The larger the taste bud, the more geniculate ganglion cells that innervated it. The relationship between ganglion cell number and taste bud volume emerged during the first 40 days postnatal. Whereas there was no difference in the average number of ganglion cells that innervated individual taste buds in rats aged 10 days postnatal through adulthood, taste bud volumes increased progressively between 10 and 40 days postnatal, at which age taste bud volumes were similar to adults. The maturation of taste bud size was accompanied by the emergence of the relationship between taste bud volume and number of innervating neurons. Specifically, there was no correlation between taste bud size and number of innervating geniculate ganglion cells in 10-, 20-, or 30-day-old rats, whereas taste bud size and the number of innervating ganglion cells in 40-day-old rats were positively correlated (r = .80, P < .002). Therefore, the relationship between taste bud size and number of innervating ganglion cells develops over a prolonged postnatal period and is established when taste buds grow to their adult size.

Afferent Pathways↗
PubMed2004

Unilateral nerve injury produces bilateral loss of distal innervation.

There are no known anatomical connections between neurons that innervate homologous right and left body parts. Nevertheless, some patients develop bilateral abnormalities after unilateral injury, a phenomenon often unrecognized and not yet characterized. Therefore, we examined in rats the effects of ligating and cutting one tibial nerve on sensory function and on density of innervation in hind paws contralaterally as well as ipsilaterally to the injury, at times between 1 day and 5 months after surgery. Punches removed from tibial- or sural-innervated planter paw skin were immunolabeled to quantitate epidermal nerve endings. Naive and sham-operated rats provided controls. Axotomized rats had near-total loss of PGP9.5(+) innervation within ipsilateral tibial-innervated skin at all time-points. Adjacent ipsilateral sural-innervated skin had persistent hyperalgesia without denervation, and robust axonal sprouting at 5 months after surgery. Contralesional hind paws lost 54% of innervation in tibial-innervated epidermis starting 1 week after surgery and persisting throughout. Contralesional sural-innervated skin had neither neurite loss nor sprouting. These results imply that unilateral nerve injury can cause profound, long lasting, nerve-branch-specific loss of distal innervation contralaterally as well as ipsilaterally. They discredit the practice of using tissues contralateral to an injury to provide normative controls and suggest the possibility of rapid, transmedian postinjury signals between homologous mirror-image neurons.

Animals↗
PubMed1979

Origin and organization of brainstem catecholamine innervation in the rat.

The catecholamine (CA) innervation of the rat brainstem was studied by biochemical analysis of discrete nuclei or areas and by glyoxylic acid-formaldehyde freeze dry fluorescence histochemistry. CA assays demonstrate that the highest norepinephrine (NE) content in brainstem is present in the trigeminal motor nucleus, nucleus tractus solitarius, dorsal motor nucleus of the vagus and nucleus raphe dorsalis. Bilateral locus coeruleus (LC) lesions do not significantly alter NE content in these nuclei but do decrease NE content in the superior and inferior colliculi, medial geniculate body, interpeduncular nucleus, pontine nuclei and the main sensory trigeminal nucleus (60-75%). Dopamine (DA) and epinephrine (E) are found in significant concentration in only a few of the nuclei examined. Fluorescence histochemical analysis indicates that two groups of NE axons innervate rat brainstem. LC neuron axons with a distinctive morphology principally innervate sensory and association nuclei of the brainstem. These disappear completely after bilateral LC lesions. The second group of axons originates from lateral and dorsal tegmental NE cell groups. Primary motor and visceral nuclei are densely innervated by fine and thick axons from these groups. Lesions of LC do not alter the NE innervation in any of the nuclei which contain axons of the second group. These results indicate that the brainstem NE innervation is divided into two major systems. The locus coeruleus complex innervates mainly primary sensory and association nuclei whereas the lateral tegmental NE neurons innervate primary motor and visceral nuclei. Although some overlap is present, the LC and lateral tegmental NE systems predominantly innervate separate and functionally distinct areas of the brainstem. DA and E neurons provide a very minor component of the brainstem CA innervation.

Animals↗
PubMed1981

Innervation and structure of extraocular muscles in the monkey in comparison to those of the cat.

Motoneurones that innervate the medial rectus, lateral rectus, and accessory lateral rectus muscles in the monkey have been identified and localized by retrograde transport of horseradish peroxidase. Medial rectus motoneurones were located within both dorsal and ventral regions of the oculomotor nucleus, with a differential distribution along the rostral-caudal axis of the nucleus. Lateral rectus motoneurones were located predominantly within the abducens nucleus, and were distributed throughout the rostral-caudal extent of the nucleus. Motoneurons that innervate the accessory lateral rectus muscle comprised a group of large cells located approximately 0.5 mm ventral to the rostral portion of the abducens nucleus, corresponding to the ventral abducens nucleus of Tsuchida ('06). The ventral subgroup of abducens motoneurones, which innervate both the lateral rectus and accessory lateral rectus muscles, thus do not occupy a motoneurones innervate the retractor bulbi muscle, to which the accessory lateral rectus muscle presumably is homologous. A few accessory lateral rectus motoneurones also were located within the abducens nucleus, overlapping the distribution of lateral rectus motoneurones. Electron microscope examination of the lateral rectus muscle revealed the presence of three morphological types of singly innervated muscle fibers and two morphological types of multiply innervated muscle fibers that exhibited a differential distribution within the orbital, intermediate, and global regions of the muscle. The accessory lateral rectus muscle resembled the global portion of the lateral rectus muscle in containing two morphological types of singly innervated fibers and one type of multiply innervated fiber. These findings indicate that the central differences in the brainstem locations of motoneurones that innervate the cat retractor bulbi and monkey accessory lateral rectus muscles are correlated with peripheral differences not only in the morphology, but also possibly in the mechanical roles, of the muscles they innervate. The accessory lateral rectus muscle thus appears to have evolved both structurally and functionally toward more of a role in patterned eye movement. Furthermore, with the phylogenetic regression of the retractor bulbi muscle, the various types of eye movement with which this muscle is associated in lower vertebrates may be assumed by the other extraocular muscles in higher mammals, including humans.

Abducens Nerve↗
PubMed1991

Serotoninergic innervation of the ferret cerebral cortex. II. Postnatal development.

We have investigated the serotoninergic innervation of the ferret cortex from the day of birth to adulthood with immunohistochemical techniques. Due to the premature birth of ferrets, this period spans the entire generation of cells located within the upper cortical layers and their subsequent migration to their final positions. Already at birth, serotoninergic fibers innervate the developing cortex. This innervation is most dense within the marginal zone, the subplate region, and the lower portion of the cortical plate. As long as cell migration continues, serotoninergic fibers enter the expanding portions of the cortex. Only the region just below the marginal zone where newly arriving cells are added to the cortical plate is not innervated by the ingrowing fibers. When the bulk of cell migration ceases, during the third postnatal week, this gap disappears and the fibers gradually form a continuous innervation from the pia to the ventricle. As the cortex matures, the serotoninergic fibers become successively confined to the upper layers, to generate the adult pattern. In the adult ferret cortex, the highest innervation density is found within layers 1, 2, and 3, with a much sparser innervation within the lower layers (Voigt and de Lima, J. Comp. Neurol. 314:403-414, 1991). The dense innervation in the deep cortical layers is only transient, virtually disappearing toward adulthood. These results suggest that serotoninergic axons innervate cortical layers as soon as newly arriving cells reach their final positions within the cortex. This early innervation lends support to the idea that serotonin may play a role during development of the cerebral cortex.

Aging↗
PubMed1993

Sequential differentiation of sensory innervation in the mystacial pad of the ferret.

The mystacial pad of the ferret has an elaborate sensory innervation provided by three types of terminal nerves that arise from the infraorbital branch of the trigeminal nerve. Deep and superficial vibrissal nerves innervate nearly exclusive targets in the large follicle-sinus complexes (F-SCs) at the base of each tactile vibrissa. Dermal plexus nerves innervate the fur between the vibrissae. Each type of nerve provides a similar variety of sensory endings, albeit to different targets. In this study, Winkelmann and Sevier-Munger reduced silver techniques revealed that most of the endings differentiate postnatally in an overlapping sequence like that observed previously in the rat. Afferents from the deep vibrissal nerves begin to differentiate first, followed successively by those from superficial vibrissal nerves and the dermal plexus. Within each type of nerve, Merkel endings begin to differentiate first, followed successively by lanceolate endings and circumferential endings. In the ferret, the differentiation of the intervibrissal fur and its innervation is slightly delayed but substantially overlaps the development of the vibrissal innervation, whereas in the rat it occurs almost entirely later. There was no evidence of a transient exuberant or misplaced innervation or other secondary remodeling. Differentiating afferents and endings are located only in the sites normally seen in the adult, suggesting a high degree of afferent-target specificity. In the ferret, innervation is virtually lacking in one target--the inner conical body of the F-SCs, which is densely innervated in the rat. This lack was due to a failure of innervation to develop rather than to a secondary elimination of a transient innervation.

Animals↗
PubMed1993

The innervation of the mystacial pad of the rat as revealed by PGP 9.5 immunofluorescence.

The innervation of the mystacial pad in the rat was investigated with the aid of antihuman protein gene product (PGP) 9.5 immunofluorescence. PGP 9.5 is ubiquitin carboxyl-terminal hydrolase, which is distributed throughout neuronal cytoplasm. This technique revealed all previously known innervation as well as a wide variety of small-caliber axons and some endings of large-caliber afferents that had not been observed before. Newly revealed innervation affiliated with vibrissal-follicle sinus complexes included 1) fine-caliber, radially oriented processes in the epidermal rete ridge collar; 2) a loose network of fine-caliber, circumferentially arrayed processes in the centrifugal part of the mesenchymal sheath at the level of the ring sinus; 3) a loose haphazard network of fine-caliber and medium-caliber processes in the mesenchymal sheath and among the trabeculae of the cavernous sinus; 4) a loose network of circumferentially arrayed processes within the mesenchymal sheath of the cavernous sinus and in close proximity to the basement membrane; 5) a dense network of reticular-like endings provided by large-caliber afferents to the mesenchymal sheath in the upper part of the cavernous sinus; and 6) fine-caliber innervation to the dermal papilla at the base of all vibrissal shafts. In the intervibrissal skin, a dense distribution of fine-caliber individual and clustered profiles was detected in the epidermis. In addition to previously known innervation, Merkel endings were consistently observed in the epidermis at the mouths of guard hairs, loose networks of fine-caliber axons were found around the necks of occasional guard hairs, and fine-caliber profiles were frequently affiliated with vellus hairs. Vascular profiles were heavily innervated throughout the dermis. Axons and motor end plates of the facial nerve innervation to papillary muscles also were labeled. Transection of the infraorbital nerve eliminated all but the facial nerve innervation. Unilateral removal of the superior cervical ganglion eliminated the innervation to the dermal papillae but caused no other noticeable reduction. PGP 9.5-like immunofluorescence was also moderately expressed in apparent Schwann cells, in Merkel cells only in the external root sheath of vibrissal follicles, and in apparent dendritic and/or Langerhans cells usually located in the epidermis and occasionally in the follicles. PGP 9.5-like immunofluorescence persisted in highly vacuolated profiles along the usual courses of medium to large-caliber axons 2 weeks after nerve transection. The possible functional role of the newly discovered innervation is considered along with that of previously identified afferents.

Animals↗
PubMedDate not supplied

Laminar, tangential and regional organization of the noradrenergic innervation of monkey cortex: dopamine-beta-hydroxylase immunohistochemistry.

An antiserum directed against human dopamine-beta-hydroxylase purified from pheochromocytoma tissue was employed in an immunohistochemical study of the organization of the noradrenergic innervation of monkey neocortex. A detailed description is given of the laminar pattern of noradrenergic innervation in the dorsolateral prefrontal cortex (Brodmann areas 9 and 10) and the primary somatosensory cortex of the postcentral gyrus (Brodmann areas 3,1,2). The noradrenergic innervation of these two regions is similar in the following respects: (1) fibers are present in all six layers, (2) the innervation is dense and terminal-like in layers IV and V, and (3) layer VI is characterized by fibers oriented parallel to the pial surface which follow the contours of the subcortical white matter. However, these regions differ with respect to specific laminar patterns of fiber distribution and orientation and by virtue of the fact that the primary somatosensory cortex has a very dense noradrenergic innervation, while the density of innervation in dorsolateral prefrontal cortex is low relative to the postcentral gyrus and most other neocortical areas. The laminar pattern of noradrenergic innervation in primary visual cortex differs fundamentally from both prefrontal and primary somatosensory cortices. In a separate series of experiments, dorsolateral frontal cortex lesions were used to investigate the intracortical trajectory of noradrenergic fibers. A discrete aspiration lesion confined to the grey matter of the prefrontal cortex led to a substantial loss of noradrenergic fibers in cortical regions caudal to the lesion. The decrease in density of noradrenergic innervation was particularly pronounced in the pre- and postcentral gyri. These results demonstrate that while the noradrenergic innervation of primate cortex exhibits a far greater degree of regional variation than is present in the rat cortex, the tangential intracortical trajectory that is characteristic of the lissencephalic rat brain is also a dominant feature of the noradrenergic innervation of the gyrencephalic primate brain.

Adrenergic Fibers↗
PubMed2003

Functional changes after prenatal opiate exposure related to opiate receptors' regulated alterations in cholinergic innervation.

Opioid drugs act primarily on the opiate receptors; they also exert their effect on other innervations resulting in non-opioidergic behavioural deficits. Similarly, opioid neurobehavioural teratogenicity is attested in numerous behaviours and neural processes which hinder the research on the mechanisms involved. Therefore, in order to be able to ascertain the mechanism we have established an animal (mouse) model for the teratogenicity induced by opioid abuse, which focused on behaviours related to specific brain area and innervation. Diacetylmorphine (heroin) and not morphine was applied because heroin exerts a unique action, distinguished from that of morphine. Pregnant mice were exposed to heroin (10 mg/kg per day) and the offspring were tested for behavioural deficits and biochemical alterations related to the septohippocampal cholinergic innervation. Some studies employing the chick embryo were concomitantly added as a control for the confounding indirect variables. Prenatal exposure to heroin in mice induced global hyperactivation both pre- and post-synaptic along the septohippocampal cholinergic innervation, including basal protein kinase C (PKC) activity accompanied by a desensitization of PKC activity in response to cholinergic agonist. Functionally, the heroin-exposed offspring displayed deficits in hippocampus-related behaviours, suggesting deficits in the net output of the septohippocampal cholinergic innervation. Grafting of cholinergic cells to the impaired hippocampus reversed both pre- and post-synaptic hyperactivity, resensitized PKC activity, and restored the associated behaviours to normality. Consistently, correlation studies point to the relative importance of PKC to the behavioural deficits. The chick model, which dealt with imprinting related to a different brain region, confirmed that the effect of heroin is direct. Taken together with studies by others on the effect of prenatal exposure to opioids on the opioidergic innervation and with what is known on the opioid regulation of the cholinergic innervation, it appears that heroin exerts its neuroteratogenicity by inducing alterations in the opioidergic innervation, which by means of its regulatory action, attenuates the functional output of the cholinergic innervation. In our model, there was hyperactivity mostly of the post-synaptic components of the cholinergic innervation. However, the net cholinergic output is decreased because PKC is desensitized to the effect of the cholinergic agonist, and this is further evidenced by the extensive deficits in the related behaviours.

Animals↗