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PubMed2005

Patterns of lower extremity innervation in pediatric spinal cord injury.

STUDY DESIGN: Retrospective review. OBJECTIVES: To identify relationships between lower extremity innervation and level of injury, mechanism of injury, and age at injury in a pediatric population with spinal cord injury (SCI). Secondarily, relationships between innervation and completeness of injury, time since injury, race, and sex were evaluated. SETTING: Pediatric orthopedic referral hospital, Philadelphia, Pennsylvania. METHODS: Records of 190 subjects, ages 1-21 years, were reviewed. Data collected from the medical record included lower extremity muscle innervation, American Spinal Injury Association (ASIA) level and class, mechanism of injury, age at injury, time since injury, race, and sex. To determine innervation, lower extremity muscles had been tested using surface electrical stimulation and identified as being innervated or denervated. If a muscle responded weakly, strength duration testing was performed. For analysis via logistic regression, subjects were grouped based upon level and mechanism of injury. RESULTS: A relationship (P<0.0001) was found between ASIA level and lower extremity innervation of all muscles and between length of time since injury and lower extremity innervation for some muscles. Following multiple logistic regression, only ASIA level remained as an independent predictor of lower extremity innervation status. CONCLUSION: Our results show that lower extremity innervation does differ based on the level of the injury. Denervation began to be seen with injuries in the lower thoracic region and more predominantly with injuries in the lumbar region. This supports our hypothesis that the incidence of lower motor neuron injuries would increase as injuries became more caudal. Our hypotheses of a relationship between innervation status and mechanism of injury and age at injury were not supported. This information is important in determining treatment strategies, eligibility for electrical stimulation techniques, and potential regenerative strategies. SPONSORSHIP: This study was funded by Shriners Hospitals for Children, Grant #8530.

Adolescent↗
PubMed1999

Localisation and quantitation of autonomic innervation in the porcine heart I: conduction system.

This study was prompted by the prospect of transgenic pigs providing donor hearts for transplantation in human recipients. Autonomic innervation is important for the control of cardiac dynamics, especially in the conduction system. Our objective was to assess the relative distribution of autonomic nerves in the pig heart, focusing initially on the conduction system but addressing also the myocardium, endocardium and epicardium (see Crick et al. 1999). Quantitative immunohistochemical and histochemical techniques were adopted. All regions of the conduction system possessed a significantly higher relative density of the total neural population immunoreactive for the general neuronal marker protein gene product 9.5 (PGP 9.5) than did the adjacent myocardium. A similar density of PGP 9.5-immunoreactive innervation was observed between the sinus node, the transitional region of the atrioventricular node, and the penetrating atrioventricular bundle. A differential pattern of PGP 9.5-immunoreactive innervation was present within the atrioventricular node and between the components of the ventricular conduction tissues, the latter being formed by an intricate network of Purkinje fibres. Numerous ganglion cell bodies were present in the peripheral regions of the sinus node, in the tissues of the atrioventricular groove, and even in the interstices of the compact atrioventricular node. Acetylcholinesterase (AChE)-containing nerves were the dominant subpopulation observed, representing 60-70% of the total pattern of innervation in the nodal tissues and penetrating atrioventricular bundle. Tyrosine hydroxylase (TH)-immunoreactive nerves were the next most abundant neural subpopulation, representing 37% of the total pattern of innervation in the compact atrioventricular node compared with 25% in the transitional nodal region. A minor population of ganglion cell bodies within the atrioventricular nodal region displayed TH immunoreactivity. The dominant peptidergic nerve supply possessed immunoreactivity for neuropeptide Y (NPY), which displayed a similar pattern of distribution to that of TH-immunoreactive nerve fibres. Calcitonin gene-related peptide (CGRP)-immunoreactive nerves represented 8-9% of the total innervation of the nodal tissues and penetrating atrioventricular bundle, increasing to 14-19% in the bundle branches. Somatostatin-immunoreactive nerve fibres were relatively sparse (4-13% of total innervation) and were most abundant in the nodes, especially the compact atrioventricular node. The total pattern of innervation of the porcine conduction system was relatively homogeneous. A substantial proportion of nerve fibres innervating the nodal tissues could be traced to intracardiac ganglia indicative of an extensive intrinsic supply. The innervation of the atrioventricular node and ventricular conduction tissues was similar to that observed in the bovine heart, but markedly different to that of the human heart. It is important that we are aware of these findings in view of the future use of transgenic pig hearts in human xenotransplantation.

Acetylcholinesterase↗
PubMed1983

Cross-innervation of fast and slow-twitch muscles by motor axons of the sural nerve in the mouse.

The extensor digitorum longus (EDL) or soleus muscles of adult mice were cross-innervated by the sural nerve (SN) and deprived of their original innervation. The number and sizes of motor units and the location of endplates in these muscles were studied 1.5 to 16 months later. In the EDL muscle, the SN cross-innervated the original endplates. Very few ectopic endplates were seen, even when the nerve was implanted well outside of the original endplate area. Only 3% of the fibres were polyneuronally innervated. In the soleus muscle, however, the SN formed large numbers of ectopic endplates whether the nerve was implanted in the original endplate zone or outside of it. In addition, 20% of the muscle fibres were polyneuronally innervated. The SN cross-innervated both EDL and soleus muscles completely. There was no preference for a particular group of the SN motoneurones since all the cross-innervated muscles were innervated by all SN motor axons and the motor unit sizes of the SN were similar in the cross-innervated EDL and soleus muscles. It is concluded that intrinsic properties of a muscle determine the ability to form ectopic synapses. The distribution of the motor unit sizes is determined by the particular pool of motoneurones which innervates the muscle.

Acetylcholinesterase↗
PubMed1976

Re-innervation of twitch and slow muscle fibres of the frog after crushing the motor nerves.

1. The conduction velocities of individual motor axons innervating twitch and slow muscle fibres of the frog were determined by intracellular recording of junctional potentials elicited by stimulating the motor nerves at two different points. 2. In normal pyriformis muscles twitch and slow fibres were found to be innervated by two distinct populations of motor axons. Twitch fibre axons conducted at 10-18-7 m/sec, while the conduction velocities of slow fibre axons ranged from 0-5 to 5 m/sec (at 7-9 degrees C). The thresholds for electrical stimulation were significantly lower in the fast than in the slow axons population. 3. Following denervation by crushing the sciatic nerve fast axons which re-innervated the muscle had lower conduction velocities than normal but could still be identified. These lower conduction velocities were measured proximal to the site of the crush and did not recover over a period of 446 days. 4. Fast motor axons regenerated more quickly than slow axons and re-innervated twitch as well as slow muscle fibres non-selectively. About 1 month later slow axons re-established synaptic contacts with slow (and some twitch) muscle fibres. Simultaneous re-innervation by fast and slow motor axons was occasionally observed in slow muscle fibres. Finally, the slow muscle fibres were innervated by slow axons only, while synapses of fast axons could no longer be found in this type of muscle fibre. 5. Action potentials were observed in denervated as well as in re-innervated slow muscle fibres; they disappeared as re-innervation progressed. 6. It is concluded that non-selective re-innervation of slow muscle fibres is present in the frog; it is, however, a transient phenomenon followed by restoration of the original innervation pattern.

Action Potentials↗
PubMed1976

Competitive and non-competitive re-innervation of mammalian sympathetic neurones by native and foreign fibres.

The ability of native (sympathetic preganglionic) and foreign (vagal) nerve fibres to re-innervate neurones of the guinea-pig superior cervical ganglion, either alone or in competition with each other, has been studied by means of intracellular recording and electron microscopy. 1. Native fibres make synaptic contacts with nearly all ganglion cells within one month of cervical trunk section; within 6 months the degree of innervation, judged by measurement of excitatory post-synaptic potential (e.p.s.p.) amplitude and electron microscopical synapse counts, approaches normal. However, even after 15 months innervation was weaker than in normal control ganglia. 2. Vagal fibres are less successful during re-innervation. Although a similar number of foreign fibres grown into denervated ganglia and make contact with nearly all ganglion cells within a month, after 6-12 months e.p.s.p. amplitudes in response to foreign nerve stimulation remain relatively small, and counts of synapses are only about 60% as great as in ganglia re-innervated with the native nerve. 3. When both native and foreign fibres are allowed to re-innervate ganglion cells simultaneously, about half the neurones in the ganglion receive synapses from both sources after 1 month. The proportion of dually invervated cells remains roughly constant for at least 14 months. Neither set of preganglionic fibres dominates or displaces the other, although neurones generally are re-innervated more effectively by native than foreign fibres, as is true during non-competitive re-innervation. 4. Thus during re-innervation of mammalian sympathetic neurones native fibres are preferred to foreign ones only in the sense that roughly the same number of native fibres form many more synapses on ganglion cells than do vagal axons. A foreign synapse, once formed, is as stable as a native one, and shows no tendency to be replaced by native terminals. These findings are discussed in relation to other evidence which has suggested specificity and selectivity during re-innervation of mammalian autonomic neurones.

Action Potentials↗
PubMed1986

Sympathetic innervation alters growth and intrinsic heart rate of fetal rat atria maturing in oculo.

The influence of sympathetic innervation on the growth and intrinsic rate of beating established by fetal rat heart was studied by culturing fetal atrial tissue in sympathetically innervated and denervated anterior eye chambers of adult Sprague-Dawley rats. One anterior eye chamber in each host rat was sympathetically denervated by removing the ipsilateral superior cervical ganglion. In oculo, atrial grafts were vascularized by blood vessels sprouting from the iris and innervated by sympathetic and parasympathetic fibers from the ground plexus of the iris. Innervation was assessed by light-activated efferent nerve stimulation to the grafts that changed their rates of beating. The norepinephrine contents of 16 atria cultured for 2.5 months in sympathetically innervated and denervated eye chambers were 5.7 +/- 1.1 ng/implant vs. 0.2 +/- 0.07 ng/implant (mean +/- SEM), indicating permanent sympathetic denervation of the anterior eye chamber and the implanted atria. By 8 weeks in oculo, atria maturing in sympathetically innervated anterior eye chambers were 86% larger than those in denervated eye chambers (2.22 +/- 0.29 vs. 1.19 +/- 0.13 mm2); the weight of innervated transplants was over 3 times that of noninnervated grafts (2.35 +/- 0.75 vs. 0.76 +/- 0.21 mg). After implanted atria had ceased growing rapidly (2.5 months in oculo), bipolar electrodes were implanted adjacent to the cornea to record impulses from atrial grafts while host rats were unanesthetized. The dark-adapted baseline heart rates of sympathetically innervated and noninnervated atria were virtually identical (289 vs. 290 bpm). Graft intrinsic heart rate was estimated by combined beta-adrenergic and muscarinic receptor blockade with atenolol (1.0 mg/kg) and methylatropine (10 micrograms/kg). Sympathetically innervated transplants had lower intrinsic heart rates than noninnervated atria (134 +/- 25 vs. 213 +/- 12 bpm). These data suggest that sympathetic innervation of the developing heart influences both growth and intrinsic rate of beating.

Animals↗
PubMed2002

Distal extension of climbing fiber territory and multiple innervation caused by aberrant wiring to adjacent spiny branchlets in cerebellar Purkinje cells lacking glutamate receptor delta 2.

Organized synapse formation on to Purkinje cell (PC) dendrites by parallel fibers (PFs) and climbing fibers (CFs) is crucial for cerebellar function. In PCs lacking glutamate receptor delta2 (GluRdelta2), PF synapses are reduced in number, numerous free spines emerge, and multiple CF innervation persists to adulthood. In the present study, we conducted anterograde and immunohistochemical labelings to investigate how CFs innervate PC dendrites under weakened synaptogenesis by PFs. In the GluRdelta2 knock-out mouse, CFs were distributed in the molecular layer more closely to the pial surface compared with the wild-type mouse. Serial electron microscopy demonstrated that CFs in the knock-out mouse innervated all spines protruding from proximal dendrites of PCs, as did those in the wild-type mouse. In the knock-out mouse, however, CF innervation extended distally to spiny branchlets, where nearly half of the spines were free of innervation in contrast to complete synapse formation by PFs in the wild-type mouse. Furthermore, from the end point of innervation, CFs aberrantly jumped to form ectopic synapses on adjacent spiny branchlets, whose proximal portions were often innervated by different CFs. Without GluRdelta2, CFs are thus able to expand their territory along and beyond dendritic trees of the target PC, resulting in persistent surplus CFs by innervating the distal dendritic segment. We conclude that GluRdelta2 is essential to restrict CF innervation to the proximal dendritic segment, by which territorized innervation by PFs and CFs is properly structured and the formation of excess CF wiring to adjacent PCs is suppressed.

Animals↗
PubMed1986

Specific innervation of neurons in the paravertebral sympathetic ganglia of the chick.

I have explored the chick sympathetic system as a model for the study of specific synapse formation by examining the pattern of ganglion cell innervation by preganglionic axons in 2 different ganglia. Using intracellular recording and HRP labeling techniques, the innervation of the 12th and 15th cervical ganglia (C12 and C15) was examined. Sympathetic ganglion cells of the chick are innervated in a stereotyped manner by preganglionic axons arising from different levels of the spinal cord. While each ganglion is innervated by preganglionic axons arising from several spinal cord segments, individual ganglion cells are innervated by only some of the spinal segments that supply each ganglion as a whole. The subset of spinal segments is always contiguous, with 1 segment providing the dominant innervation to the cell. Spinal segments adjacent to the dominant segment provide synaptic inputs that diminish as a function of distance from the dominant segment. This pattern of ganglion cell innervation in the chick is similar to that of the mammal, where re-innervation studies have suggested that ganglion cell innervation is selective. The similarity in the innervation of avian and mammalian sympathetic neurons suggests that the rules that underlie the specificity of synapse formation in the sympathetic system of the 2 species are the same. Because of the accessibility of the chick embryo for experimental manipulations during development, it is now possible to study the cellular basis that underlies the specificity of synapse formation in this relatively simple nervous system.

Animals↗
PubMed1979

Development of the segmental innervation of the chick forelimb.

A number of recent studies have shown that during embryonic development the initial innervation of a target structure may be made up, in part, by axons which do not form part of the mature innervation of that structure. In the present study we have examined the motor innervation of the major muscles of the chick forelimb at different stages of development using HRP-uptake-labelling of motoneurons, electrophysiological recording and measurement of muscle contraction. In the mature White Leghorn chick the major contribution to the motor innervation of the forelimb is from spinal segments 14, 15 and 16. Using the HRP-labelling technique we have shown that at stages 26-29 of development motoneurons in segments 12-17 have axon terminals in the presumptive biceps muscle. Between stages 30 and 35, however, the axon terminals arising from segments 12, 13, 16 and 17 are lost, leaving the mature innervation from segments 14 and 15. We have also observed the loss of innervation of the biceps muscle by segment 16 using electrophysiological recording of compound action potentials in the biceps nerve and by measurement of the local contraction of the biceps muscle in response to stimulation of the segmental nerves. Similar changes in the innervation of the triceps, extensor metacarpi radialis, flexor carpi ulnaris and flexor digitorum profundus muscles have also been observed. These results are discussed in relation to the hypothesis that (i) the motoneuron pools and muscles in the developing spinal cord and forelimb are matched, (ii) that some axons which arrive in a particular muscle during early development are unable to form a stable connexion and (iii) that the inability of an axon terminal to form a stable connexion in a muscle results in the death of the motoneuron. Intracellular recording from muscle cells at stage 35 shows that the synaptic site on each cell is innervated by about three separate axons. Over the next few stages, however, all but one of the innervating axons is lost. From our contraction studies it is clear that the removal of the excess axon terminals after stage 35 is not associated with the establishment of the mature segmental innervation pattern of the muscle.

Action Potentials↗
PubMed1996

Selective innervation of fast and slow muscle regions during early chick neuromuscular development.

The electrical properties of adult motoneurons are well matched to the contractile properties of the fast or slow muscle fibers that they innervate. How this precise matching occurs developmentally is not known. To investigate whether motoneurons exhibit selectivity in innervating discrete muscle regions, containing either fast or slow muscle fibers during early neuromuscular development, we caused embryonic chick hindlimb muscles to become innervated by segmentally inappropriate motoneurons. We used the in vitro spinal cord-hindlimb preparation to identify electrophysiologically the pools of foreign motoneurons innervating the posterior iliotibialis (pITIB), an all-fast muscle, and the iliofibularis (IFIB), a partitioned muscle containing discrete fast and slow regions. The results showed that the pITIB and the fast region of the IFIB were exclusively innervated by motoneurons that normally supply fast muscles. In contrast, the slow region of the IFIB was always innervated by motoneuron pools that normally supply slow muscles. Some experimental IFIB muscles lacked a fast region and were innervated solely by "slow" motoneurons. In addition, the intramuscular nerve branching patterns were always appropriate to the fast-slow nature of the muscle (region) innervated. The selective innervation was found early in the motoneuron death period, and we found no evidence that motoneurons grew into appropriate muscle regions, but failed to form functional contacts. Together, these results support the hypothesis that different classes of motoneurons exhibit molecular differences that allow them to project selectively to, and innervate, muscle fibers of the appropriate type during early neuromuscular development.

Animals↗
PubMed1997

Comprehensive immunofluorescence and lectin binding analysis of vibrissal follicle sinus complex innervation in the mystacial pad of the rat.

The innervation of the vibrissal follicle sinus complexes (FSCs) in the mystacial pad of the rat was examined by lectin binding histofluorescence with the B subunit of Griffonia simplicifolia (GSA) and by immunofluorescence with a wide variety of antibodies for neuronal related structural proteins, enzymes, and peptides. Only anti-protein gene product 9.5 labeled all sets of innervation. Several types of mechanoreceptors were distributed to specific different targets by medium to large caliber myelinated axons. All were positive for 200 kDa neurofilament subunit, peripherin, and carbonic anhydrase. Their endings expressed synaptophysin. Labeling for the 160 kDa neurofilament subunit, calbindin, and parvalbumin varied. Anti-Schwann cell protein S100 was completely co-extensive with the axons, terminal arbors, and endings of the mechanoreceptor afferents including Merkel innervation. At least 15 different sets of unmyelinated innervation were evident based upon distribution and labeling characteristics. They consisted of four basic types: 1) peptidergic; 2) GSA binding; 3) peptidergic and GSA binding; and 4) nonpeptidergic and GSA negative (peptide-/GSA-). Previous studies had not revealed that several major sets of unmyelinated innervation were peptide-/GSA-. The unmyelinated innervation had detectable peripherin but not 160 kDa or 200 kDa neurofilament subunits. GSA-positive axons uniquely lacked anti-S100 immunoreactivity. The dense circumferentially oriented unmyelinated innervation of the inner conical body contained major sets of peptide-/GSA- and GSA innervation as well as a smaller peptidergic GSA component. A small contingent of sympathetic and possibly parasympathetic innervation was affiliated with microvasculature in the FSCs. This study confirms and refutes some previous hypotheses about biochemical and morphological relationships between peripheral innervation and sensory ganglion cells.

Animals↗
PubMed1998

Differential dependency of unmyelinated and A delta epidermal and upper dermal innervation on neurotrophins, trk receptors, and p75LNGFR.

The impact of the nerve growth factor (NGF) family of neurotrophins and their receptors was examined on the cutaneous innervation in the mystacial pads of mice. Ten sets of unmyelinated and thinly myelinated sensory and autonomic innervation were evaluated that terminated in the epidermis, upper dermis, and upper part of the intervibrissal hair follicles. Mystacial pads were analyzed from newborn to 4-week-old mice that had homozygous functional deletions of the genes for NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), tyrosine kinase (trk) A, trkB, trkC, or p75. Mystacial pads were also analyzed in adult transgenic mice that had overproduction of NGF, BDNF, or NT-3 driven by a keratin promoter gene. The innervation was revealed by using immunofluorescence and immunocytochemistry with antibodies for protein gene product (PGP) 9.5, calcitonin gene-related product (CGRP), substance P (SP), galanin (GAL), neuropeptide Y (NPY), tyrosine hydroxylase (TH), and a neurofilament protein. The cumulative results indicated that NGF/trkA signaling plays a major role in the outgrowth and proliferation of sensory axons, whereas NT-3/ trkA signaling plays a major role in the formation of sensory endings. TrkC is also essential for the development of three sets of trkA-dependent sensory innervation that coexpress CGRP, SP, and GAL. Another set of sensory innervation that only coexpressed CGRP and SP was solely dependent upon NGF and trkA. Surprisingly, most sets of trkA-dependent sensory innervation are suppressed by trkB perhaps interacting with p75. BDNF and NT-4 appear to mediate this suppressing effect in the upper dermis and NT-4 in the epidermis. In contrast to sensory innervation, sympathetic innervation to the necks of intervibrissal hair follicles depends upon NGF/trkA signaling interacting with p75 for both the axon outgrowth and ending formation. Although NT-3/trkA signaling is essential for the full complement of sympathetic neurons, NT-3 is detrimental to the formation of sympathetic terminations to the necks of hair follicles. TrkB signaling mediated by BDNF but not NT-4 also suppresses these sympathetic terminations. One sparse set of innervation, perhaps parasympathetic, terminating at the necks of hair follicles is dependent solely upon NT-3 and trkC. Taken together, our results indicate that the innervation of the epidermis, upper dermis, and the upper portion of hair follicles is regulated by a competitive balance between promoting and suppressing effects of the various neurotrophins.

Animals↗
PubMed1990

Abnormalities of aneural and innervated cultured muscle fibers from patients with myotonic atrophy (dystrophy).

Innervation of human muscle cocultured in monolayer with explants of fetal rat spinal cord plus dorsal-root ganglia produces more mature fibers, which show spontaneous, neurogenic (d-tubocurarine-blocked) contractions. On the innervated myotonic atrophy (MA) muscle fibers, 96% of acetylcholinesterase-stained patches were simple, and only 4% appeared as complicated, pretzel-like, more mature-looking structures; on control innervated fibers, 37% of the acetylcholinesterase patches had the mature appearance. The normal trend from multifocal innervation toward unifocal innervation was decreased in innervated MA muscle fibers. Microelectrode studies compared parameters of cultured aneural muscle fibers and cultured innervated-contracting muscle fibers from 7 patients with MA and 10 control patients. The mean resting membrane potentials of the two groups (aneurally cultured MA muscle fibers and innervated-contracting cultured MA muscle fibers) were 8 and 9 mV lower, respectively, than those of their counterpart controls. The mean amplitude of action potentials, the maximum rate of rise of action potentials in innervated MA muscle fibers, and the action potential amplitude in aneural MA muscle fibers were significantly smaller than in corresponding control fibers.

Acetylcholinesterase↗
PubMed1997

Comprehensive immunofluorescence and lectin binding analysis of intervibrissal fur innervation in the mystacial pad of the rat.

The innervation of the intervibrissal fur in the mystacial pad of the rat and mouse was examined by immunofluorescence with a wide variety of antibodies for neuronal related structural proteins, enzymes, and peptides as well as for lectin binding histofluorescence with Griffonia simplicifolia (GSA). Anti-protein gene product 9.5 (PGP) immunofluorescence labeled all sets of axons and endings. The innervation in the upper dermis and epidermis was distributed through a four tiered dermal plexus. From deep to superficial, the second tier was the source of all apparent myelinated mechanoreceptors, the third tier of nearly all the peptidergic and GSA binding innervation, and the fourth tier of nonpeptidergic GSA negative innervation (peptide-/GSA-). Three types of mechanoreceptors-Merkel, transverse lanceolate, and longitudinal lanceolate endings-innervated guard hair follicles. All had similar labeling characteristics for 160 kDa and 200 kDa neurofilament subunits, peripherin, carbonic anhydrase, synaptophysin, and S100. Palisades of longitudinal lanceolate endings were part of piloneural complexes along circumferentially oriented sets of transverse lanceolate endings, peptidergic free nerve endings (FNEs), and peptide-/GSA- FNEs. The longitudinal lanceolate endings were the only mechanoreceptors in the mystacial pad that had detectable calcitonin gene-related peptide. The epidermis contained four types of unmyelinated endings: simple free nerve endings (FNEs), penicillate endings, cluster endings and bush endings. Only the simple FNEs were clearly peptidergic. Virtually all others were peptide-/ GSA-. Each bush ending was actually an intermingled cluster of endings formed by several unmyelinated axons and occasionally an Adelta axon. In contrast to the other unmyelinated innervation to the epidermis, bush endings labeled with an antibody against the Schwann cell protein S100. The necks and mouths of follicles, as well as superficial vasculature, were innervated by a mixture of unmyelinated peptidergic and/or GSA labeled sensory and sympathetic axons. Small presumptive sweat glands were innervated by three sets of peptidergic axons of which one was immunoreactive for somatostatin. Potential functions of the various sets of innervation are discussed.

Animals↗
PubMed2000

Innervation of the digit on the forepaw of the raccoon.

The innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin-gene related peptide, substance P, neuropeptide-Y, tyrosine hydroxylase, and neurofilament protein. The larger-caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine-caliber innervation terminates in the epidermis and on the microvasculature. The innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffini-like endings at the transition from the distal phalanx and unmyelinated innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine-caliber innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular innervation is peptidergic, whereas most of the unmyelinated epidermal innervation is nonpeptidergic.

Animals↗
PubMed1990

Further serial transmission electron microscopy studies of auditory hair cell innervation in lizards and in a snake.

Auditory hair cells of three lizard and one snake species were studied by serial transmission electron microscopy (TEM) sections of two unidirectional hair cells (UHC) and two bidirectional hair cells (BHC) and by nonserial section montages of each entire papilla cut at 2-microns intervals across the papillar width. The unidirectional hair cell region of the agamid lizard, Acanthosaura crucigera, lacked efferent innervation. Another agamid lizard, Agama agama, studied by nonserial section only, also lacked efferent innervation to the UHC. Afferent innervation to both the UHC and BHC of Acanthosaura was primarily exclusive (each nerve fiber innervates only one hair cell), although an occasional nerve fiber innervated two hair cells. Both the UHC and the BHC of the anguid, Celestus costatus, were exclusively innervated. Both hair cell types of the varanid, Varanus exanthematicus, were nonexclusively innervated (all afferent nerve fibers innervate two or more hair cells). The auditory papilla of the colubrid snake, Elaphe obsoleta, has only one type of hair cell and each is nonexclusively innervated. The numbers of afferent and efferent nerve fibers and of afferent synapses are presented in tabular form.

Animals↗
PubMed2003

GABAergic and glutamatergic axons innervate the axon initial segment and organize GABA(A) receptor clusters of cultured hippocampal pyramidal cells.

We have studied gamma-aminobutyric acid (GABA)(A) receptor (GABA(A)R) clustering within the axon initial segment (AIS) in low-density cultures of hippocampal pyramidal cells following GABAergic and glutamatergic innervation of the AIS. Large, intensely fluorescent, and postsynaptic GABA(A)R clusters were present in the AIS. More than 95% of these clusters colocalized with presynaptic GABAergic or glutamatergic terminals, forming matched or mismatched synapses, respectively. Less than 5% of the GABA(A)R clusters of the AIS did not colocalize with GABAergic or glutamatergic terminals, suggesting that GABA(A)Rs normally do not form clusters unless the AIS received GABAergic or glutamatergic innervation. Few or no clusters of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors or the postsynaptic density-95 protein (PSD-95) were found in the AIS, even when the AIS was innervated by glutamatergic axons. Glutamatergic innervation of the AIS that formed mismatched synapses with postsynaptic GABA(A)R clusters mainly occurred when the AIS did not receive GABAergic innervation. However, when the AIS was innervated by GABAergic axons, the formation of matched GABAergic synapses predominated and coincided with large reductions in both the density of glutamatergic terminals from the AIS and the mismatching of GABA(A)R clusters. A similar effect was observed at axo-dendritic synapses, where GABAergic innervation also led to a large decrease in mismatched GABA(A)R clusters and a smaller, but significant, decrease in glutamatergic terminal density in dendrites that received GABAergic innervation. We hypothesize that competition between GABAergic and glutamatergic innervation of the AIS in the intact hippocampus leads to the exclusive presence of GABAergic inhibitory synapses in the AIS of pyramidal cells.

Animals↗
PubMed1984

Autonomic nervous system innervation of thymic-related lymphoid tissue in wildtype and nude mice.

A study was undertaken to determine the source and terminal distribution of the autonomic nervous system (ANS) innervation of lymphoid tissue in the mediastinum of male and female B10 and Balb/c wildtype and syngeneic nude (nu/nu) mice. Acetylcholinesterase (AChE) histochemistry was used to localize this hydrolytic enzyme in neural tissue and glyoxylic acid fluorescent histochemistry was used to characterize catecholaminergic (CA) innervation. The thymus was innervated by AChE-positive fibers of the vagus, the recurrent laryngeal, and the phrenic nerves. Catecholaminergic innervation was derived from the stellate ganglia and other small ganglia of the thoracic sympathetic nervous system chain. Whereas intrinsic AChE-positive innervation of the thymus was evident at the cortico-medullary boundaries and under the capsule, CA innervation was observed along the trabeculae with perivascular plexuses at the cortico-medullary boundaries and interlobular septa. Free CA fibers were noted in the medulla and in the cortex, where they were often proximal to cortical autofluorescent (CAF) cells. The rudimentary thymus of the adult nude mouse received limited ANS innervation. Only a few CA or AChE-positive fibers were evident, with the majority of fibers associated with the acinar cells of the gland. Mediastinal lymph nodes in male and female wildtype mice varied in their distribution and were frequently found clustered around nerves and ganglia. The intrinsic innervation of lymph nodes by AChE-positive fibers was confined to the subcapsular marginal sinus, with a few vascular-associated fibers in the parenchyma. Catecholaminergic perivascular plexuses were present in the hilar zone, whereas some free fibers were noted under the capsule and in the parenchyma. The mediastinal lymph nodes of male and female nude mice when compared to the lymph nodes of male and female wildtype mouse were found to be increased in number and in distribution. Clusters of these lymph nodes were found in close proximity to ANS tissue. The intrinsic innervation of the nude mediastinal lymph nodes was comparable to that present in the wildtype mouse tissue. The functional implication of these data is discussed with regard to nervous:immune system interactions.

Acetylcholinesterase↗