Extrinsic Sources Research Articles

Dichronous appearance and unusual origins of GABA neurons during development of the mammalian thalamus

These studies in fetal monkeys and ferrets show that the two fundamental types of thalamic GABA neuron populate the thalamus during widely separated developmental epochs. Those of the ventral thalamus (VT) and epithalamus (ET) appear very early in conjunction with the GABA cells of the substantia nigra, globus pallidus, and pretectum (PT). GABA neurons intrinsic to the dorsal thalamus (DT) appear later, long after proliferative activity has ceased in the wall of the third ventricle, after dorsal thalamic nuclei have differentiated and at the same time as principal neurons are acquiring a glutamatergic phenotype. The exact origins of the two waves of GABA cells are uncertain but some appear to arrive from extrinsic sources that include the ganglionic eminence (GE) of the basal forebrain.

Carbon acceptor doping efficiency in GaAs grown by metalorganic chemical vapor deposition

Carbon doping efficiency in GaAs grown by metalorganic chemical vapor deposition using intrinsic and extrinsic doping sources is studied. Independent of the carbon source, carbon hydrogen complexes are systematically present and depending on the growth conditions, carbon dimers can be present and form complexes with hydrogen as well. Carbon–hydrogen related complexes and dimers reduce the hole concentration decreasing the doping efficiency. Additionally, the carbon dimer introduces a deep level, decreases the hole mobility and hydrogen bonds stronger to it than to isolated carbon. Depending on the growth conditions it is possible to reach 100% doping efficiency with high hole mobility.

Atrial Natriuretic Peptide-like Immunoreactivity in Neurons and Astrocytes of Human Cerebellum and Inferior Olivary Complex

Atrial natriuretic peptide (ANP) has previously been localized in areas of mammalian brain associated with olfaction, cardiovascular function, and fluid/electrolyte homeostasis. Despite the presence of several types of natriuretic peptide receptors in mammalian cerebellum, neither intrinsic nor extrinsic sources of the natriuretic peptides have been described. In this report we describe the immunohistochemical localization of both intrinsic and extrinsic sources for ANP in human cerebellum. ANP-like immunoreactivity (ANP-LIR) was observed in climbing fibers in the cerebellar molecular layer that probably originated from isolated immunopositive neurons of the inferior olivary complex. Intrinsic sources of ANP-LIR included small subpopulations of protoplasmic and fibrous astrocytes and Bergmann glia, as well as Golgi and Lugaro neurons of the granule cell layer. These results suggest that, in addition to its presumptive roles in local vasoregulation, ANP may serve as a modulator of the activity of Purkinje neurons.

Redox regulation in human melanocytes and melanoma.

The human melanocyte is continuously exposed to intrinsic and extrinsic sources of reactive biochemical species, but is finely tuned via the intrinsic anti-oxidant and radical properties of melanin to suppress the build-up of an altered redox phenotype. We propose that this control is lost during melanomagenesis and inappropriate redox-sensitive transcriptional factor activations occur which result in enhancement of an anti-apoptotic phenotype in the transformed cell. This conceptual framework offers testable steps to determine the role of redox alterations in the carcinogenic evolution, prevention and treatment of melanoma and other diseases of the melanocyte.

Domain wall motion and its contribution to the dielectric and piezoelectric properties of lead zirconate titanate films

In this article, domain wall motion and the extrinsic contributions to the dielectric and piezoelectric responses in sol–gel derived lead zirconate titanate (PZT) films with compositions near the morphotropic phase boundary were investigated. It was found that although the films had different thicknesses, grain sizes, and preferred orientations, similar intrinsic dielectric constants were obtained for all films between 0.5 and 3.4 μm thick. It was estimated that about 25%–50% of the dielectric response at room temperature was from extrinsic sources. The extrinsic contribution to the dielectric constant of PZT films was mainly attributed to 180° domain wall motion, which increased with both film thickness and grain size. In studies on the direct and converse longitudinal piezoelectric coefficients of PZT films as a function of either stress or electric driving field, it was found that the ferroelastic non-180° domain wall motion was limited. Thus extrinsic contributions to the piezoelectric response were small in fine grain PZT films (especially those under 1.5 μm in thickness). However, as the films became thicker (>5μm), nonlinear behavior between the converse piezoelectric coefficient and the electric driving field was observed. This indicated that there was significant ferroelectric non-180° domain wall motion under high external excitation in thicker films. The activity of the non-180° domain walls was studied through non-180° domain switching. For fine grain films with film thicknesses less than 2 μm, non-180° switching was negligible. Transmission electron microscopy plan-view micrographs evidenced non-180° domain fringes in these films, where the vast majority of grains were 50–100 nm in diameter and showed a single set of domain fringes. Taken together, these measurements suggest that the pinning of non-180° domain walls is very strong in films with thickness less than 2 μm. In thicker films, non-180° domain switching was evidenced when the poling field exceeded a threshold field. The threshold field decreased with an increase in film thickness, suggesting more non-180° domain wall mobility in thicker films. Non-180° domain switching in large grained PZT films was found to be much easier and more significant than in the fine grained PZT films.

VIP innervation: sharp contrast in fetal sheep and baboon adrenal glands suggests differences in developmental regulation

Immunocytochemical technique and light microscopy were used to ascertain the relationship between vasoactive intestinal polypeptide (VIP) and tyrosine hydroxylase in fetal sheep and fetal baboon adrenal cortices and medullae at 85% of gestation. VIP immunostaining was extremely robust in fetal sheep adrenal cortical neurofibers and cells while weak in fibers and nonexistent in cells of fetal baboon. Also, tyrosine hydroxylase-immunopositive cells, present throughout the adrenal cortices of both fetal sheep and baboons, were heavily innervated by VIP-immunoreactive neurofibers in fetal sheep, but not in fetal baboons. Adrenal cortical VIP-immunopositive fibers occurred in greater ( P<0.05) frequency in fetal sheep than in fetal baboons (14.82±3.10 vs. 0.84±0.26 fibers/field), were larger in diameter (2.93±0.34 vs. 0.93±0.07 μm) and ran for longer distances in the plane of section (127.85±5.16 vs. 74.53±4.93 μm). VIP immunogenicity in cells (ganglion and chromaffin) and fibers was robust in fetal adrenal medulla of sheep while nonexistent in baboons. VIP fibers in fetal sheep medulla were smaller in diameter compared to fetal sheep cortex (1.22±0.13 vs. 2.93±0.34 μm, P<0.05), but not compared to extrinsic nerve fibers (1.30±0.09 μm). We hypothesize that in fetal sheep of this age, medullary neurofibers derive primarily from extrinsic sources while cortical fibers arise from cortical ganglion cells. We conclude that at 85% of gestation the potential for VIP neural control of paracrine (e.g., glucocorticoid/catecholamine) interactions in both adrenal cortex and medulla is much greater in fetal sheep compared to fetal baboons.

Types of neurons in the enteric nervous system

This paper, written for the symposium in honour of more than 40 years’ contribution to autonomic research by Professor Geoffrey Burnstock, highlights the progress made in understanding the organisation of the enteric nervous system over this time. Forty years ago, the prevailing view was that the neurons within the gut wall were post-ganglionic neurons of parasympathetic pathways. This view was replaced as evidence accrued that the neurons are part of the enteric nervous system and are involved in reflex and integrative activities that can occur even in the absence of neuronal influence from extrinsic sources. Work in Burnstock’s laboratory led to the discovery of intrinsic inhibitory neurons with then novel pharmacology of transmission, and precipitated investigation of neuron types in the enteric nervous system. All the types of neurons in the enteric nervous system of the small intestine of the guinea-pig have now been identified in terms of their morphologies, projections, primary neurotransmitters and physiological identification. In this region there are 14 functionally defined neuron types, each with a characteristic combination of morphological, neurochemical and biophysical properties. The nerve circuits underlying effects on motility, blood flow and secretion that are mediated through the enteric nervous system are constructed from these neurons. The circuits for simple motility reflexes are now known, and progress has been made in analysing those involved in local control of blood flow and transmucosal fluid movement in the small intestine.

Changes in the Structure of Dentine from Cheek Teeth of Deer Chronically Exposed to High Levels of Environmental Fluoride

The purpose of this study was to examine, using backscattered electron imaging, the changes occurring in the structure of the dentine including giant tubules in the teeth of deer chronically exposed to fluoride. The primary and secondary dentine was characterised by the presence of interglobular dentine and regular bands of hypo- and hypermineralised dentine. Giant tubules in the unworn teeth of animals exposed to low and high levels of fluoride were characterised by a large lumen and hypermineralised rim in which there were calcospherites. With the occlusal wear of the teeth tubules beneath the immediate surface of the exposed dentine in teeth from fluorotic animals became occluded with mineral, but in low fluoride animals some tubules at the surface were not occluded with mineral. It is suggested that mineral which occludes the tubules may come from both intrinsic and extrinsic sources. The presence of some open tubules at the immediate surface in the worn teeth of animals exposed to low fluoride suggests an extrinsic source for this mineral.

Helicobacter pylori infection reduces intraluminal nitric oxide in humans.

It has recently been demonstrated that nitric oxide (NO) is highly concentrated in the gastric lumen and plays an important role in defending against pathogenic microorganisms in the stomach. NO in the gastric lumen is mainly delivered by extrinsic sources from saliva. We studied whether Helicobacter pylori infection affected intraluminal NO levels in humans. H. pylori infection was diagnosed on the basis of histology and culture or (13C)-urea breath test. Air and gastric juice in the gastric lumen were collected endoscopically. The concentration of intraluminal NO was measured by a chemiluminescence system, using an NO analyzer. The concentration of nitrite in gastric juice was measured by the Griess reaction. The intraluminal concentration of NO in H. pylori-positive patients (198.2 +/- 41 parts per billion [ppb] mean +/- SE; n = 70) was significantly lower than that in H. pylori-negative patients (353.0 +/-57.9ppb; n = 43; P < 0.05). In contrast, the concentration of nitrite in gastric juice in H. pylori-positive patients (57.7 +/- 12.3 RM; n = 70) was significantly higher than that in H. pylori-negative patients (25.9 +/- 6.4 microM; n = 43, P < 0.01). The intraluminal concentration of NO in H. pylori-positive patients was markedly increased and the concentration of nitrite in H. pylori-positive patients was markedly decreased following the completion of eradication therapy. Based on these results, we propose that a decrease in NO and excess nitrite production in the gastric lumen are associated with H. pylori infection and may play an important role in the pathogenesis of H. pylori-related abnormalities.

Imaging field-dependent structure in charge-density waves by X-ray diffraction topography

We have imaged field-dependent CDW structure in NbSe 3 single crystals by X-ray diffraction topography. Just above E T , the CDW shears along longitudinal steps in crystal thickness associated with small-angle grain boundaries, and at high fields transverse correlations recover. These results demonstrate X-ray topography as an effective probe of CDW structure, and together with earlier transport measurements establish that extrinsic sources dominate the most obvious manifestations of plasticity in this CDW conductor.

Imaging Shear in Sliding Charge-Density Waves by X-Ray Diffraction Topography

We have imaged the electric-field-dependent structure of charge-density waves (CDWs) in ribbonlike ${\mathrm{NbSe}}_{3}$ single crystals by monochromatic x-ray topography. Below the depinning threshold ${E}_{T}$ the CDW is well correlated. Just above ${E}_{T}$, the CDW shears along longitudinal steps in crystal thickness associated with small-angle grain boundaries, and at high fields transverse correlations recover. These results demonstrate x-ray topography as an effective probe of superlattice structure and with earlier transport measurements establish that extrinsic sources dominate CDW plasticity observed in ${\mathrm{NbSe}}_{3}$.

Autologous chondrocyte transplantation.

The intrinsic capacity of cartilage to repair chondral injuries is poor. Different techniques to induce cartilage repair with the use of extrinsic chondrogeneic cell sources have been explored in experimental models. Cells can be harvested autologously or as allografts from a healthy part of the donor tissue, isolated, expanded in vitro, and finally implanted into the defect in high densities. Pure chondrocytes, epiphyseal or mature, allogeneic or autologous, and other types of mesenchymal cells have been used. The composition and structure of the extracellular cartilage matrix are maintained through a balance of anabolic and catabolic activities controlled by the unique chondrocytes. They keep the cartilage alive; they alone maintain it and regulate it. It therefore seems important to use true committed chondrocytes to repair a local cartilaginous defect. The rational basis for the use of committed autologous chondrocytes in combination with a covering periosteal membrane in the treatment of deep cartilage defects is presented.

The site of origin of calcitonin gene-related peptide-like immunoreactive afferents to the inferior olivary complex of the mouse.

The intent of the present study is to define the brainstem nuclei which give rise to CGRP-immunolabeled afferents to the inferior olivary complex of the mouse. A technique which combines retrograde transport of fluorescent microspheres with immunohistochemistry was used to address this question. In the present study, intensely labeled CGRP neurons were localized within several cranial nerve nuclei including the hypoglossal, facial, oculomotor, motor nucleus of the trigeminal nerve and nucleus ambiguus, as well as in the parabrachial nucleus, locus coeruleus and medullary and pontine reticular formation. In addition, lightly labeled CGRP neurons were identified within the deep cerebellar nuclei, the inferior olivary complex, lateral reticular nucleus, medial and lateral vestibular nuclei, nucleus Darkschewitsch, interstitial nucleus of Cajal, the central gray area adjacent to the third ventricle, and the zona incerta. The origin of the projection to the inferior olivary complex primarily arises from the deep cerebellar nuclei, the locus coeruleus, and the central gray matter of the mesodiencephalic area. In addition, a small CGRP input is derived from the superior and lateral vestibular nuclei as well as the zona incerta. In conclusion, we have identified several extrinsic sources of CGRP to the inferior olivary complex and have localized it within afferents that have been shown to have either excitatory (mesodiencephalic nuclei) or inhibitory (cerebellar nuclei) effects on olivary circuits. The presence of CGRP in these functionally diverse brainstem and cerebellar afferents suggests that the peptide may act as a co-transmitter to modulate the activity of olivary neurons.

Parvalbumin-immunoreactive axon terminals in macaque monkey and human prefrontal cortex: Laminar, regional, and target specificity of type I and type II synapses

In sensory regions of primate neocortex, the calcium-binding protein parvalbumin (PV) is present in axon terminals that form both Gray's type I (asymmetric) and type II (symmetric) synapses. Those terminals forming type I synapses appear to arise from relay nuclei in the thalamus, whereas those forming type II synapses derive from cortical local circuit neurons. However, whether PV is present in both of these two types of terminals in the association regions of the primate prefrontal cortex (PFC) is not known. In the present study, PV-immunoreactive (IR) axon terminals in the superficial layers (layers 2-3a) of monkey PFC area 9 were found to form exclusively type II synapses onto the dendritic spines (44%), shafts (39%), or somata/axon initial segments (17%) of pyramidal neurons. In contrast, in the middle layers (layers 3b-4), 52% of the PV-IR axon terminals formed type I synapses, and 79% of these terminals contacted dendritic spines. However, in the adjacent area 46, only 12% of the PV-IR terminals in the middle layers formed type I synapses. In addition, the PV-IR axon terminals forming type I synapses were 50% larger than those terminals forming type II synapses. Similar to the macaque monkey, in area 9 of the human PFC, PV-IR axon terminals forming type I synapses onto dendritic spines were found in the middle layers. These findings indicate that PV-IR axon terminals in macaque monkey and human PFC are likely to have both intrinsic and extrinsic sources. In addition, the laminar, regional, and target specificity of the labeled terminals forming type I synapses suggests that they arise from PV-IR neurons in the mediodorsal thalamic nucleus.

Fine structural analysis of calcitonin gene-related peptide in the mouse inferior olivary complex.

Climbing fiber afferents to the cerebellum, from the inferior olivary complex, have a powerful excitatory effect on Purkinje cells. Changes in the responsiveness of olivary neurons to their afferent inputs, leading to changes in the firing rate or pattern of activation in climbing fibers, have a significant effect on the activation of cerebellar neurons and ultimately on cerebellar function. Several neuropeptides have been localized in both varicosities and cell bodies of the mouse inferior olivary complex, one of which, calcitonin gene related peptide (CGRP), has been shown to modulate the activity of olivary neurons. The purpose of the present study was to investigate the synaptic relationships of CGRP-containing components of the caudal medial accessory olive and the principal olive of adult mice, using immunohistochemistry and electron microscopy. The vast majority of immunoreactive profiles were dendrites and dendritic spines within and outside the glial boundaries of synaptic glomeruli (clusters). Both received synaptic inputs from non-CGRP labeled axon terminals. CGRP was also present within the somata of olivary neurons as well as in profiles that had cytological characteristics of axons, some of which were filled with synaptic vesicles. These swellings infrequently formed synaptic contacts. At the LM level, few, if any, CGRP-immunoreactive climbing fibers, were seen, suggesting that CGRP is compartmentalized within the somata and dendrites of olivary neurons and is not transported to their axon terminals. Thus, in addition to previously identified extrinsic sources of CGRP, the widespread distribution of CGRP within olivary somata and dendrites identifies an intrinsic source of the peptide suggesting the possibility of dendritic release and a subsequent autocrine or paracrine function for this peptide within olivary circuits.

The cellular mechanism by which the dermomyotome contributes to the second wave of myotome development.

We have shown that a subset of early postmitotic progenitors that originates along the medial part of the epithelial somite gives rise to the primary myotome (Kahane, N., Cinnamon, Y. and Kalcheim, C. (1998). Mech. Dev. 74, 59-73). Because of its postmitotic nature, further myotome expansion must be achieved by cell addition from extrinsic sources. Here we investigate the mechanism whereby the dermomyotome contributes to this process. Using several different methods we found that cell addition occurs from both rostral and caudal edges of the dermomyotome, but not directly from its dorsomedial lip (DML). First, labeling of quail embryos with [3H]thymidine revealed a time-dependent entry of radiolabeled nuclei into the myotome from the entire rostral and caudal lips of the dermomyotome, but not from the DML. Second, fluorescent vital dyes were injected at specific sites in the dermomyotome lips and the fate of dye-labeled cells followed by confocal microscopy. Consistent with the nucleotide labeling experiments, dye-labeled myofibers directly emerged from injected epithelial cells from either rostral or caudal lips. In contrast, injected cells from the DML first translocated along the medial boundary, reached the rostral or caudal dermomyotome lips and only then elongated into the myotome. These growing myofibers had always one end attached to either lip from which they elongated in the opposite direction. Third, following establishment of the primary myotome, cells along the extreme dermomyotome edges, but not the DML, expressed QmyoD, supporting the notion that rostral and caudal boundaries generate myofibers. Fourth, ablation of the DML had only a limited effect on myotomal cell number. Thus, cells deriving from the extreme dermomyotome lips contribute to uniform myotome growth in the dorsoventral extent of the myotome. They also account for its expansion in the transverse plane and this is achieved by myoblast addition in a lateral to medial direction (from the dermal to the sclerotomal sides), restricting the pioneer myofibers to the dermal side of the myotome. Taken together, the data suggest that myotome formation is a multistage process. A first wave of pioneers establishes the primary structure. A second wave generated from specific dermomyotome lips contributes to its expansion. Because dermomyotome lip progenitors are mitotically active within the epithelia of origin but exit the cell cycle upon myotome colonization, they can only provide for limited myotome growth and subsequent waves must take over to ensure further muscle development.

Testing the relative influence of instrinsic and extrinsic variation in food availability on feral pig populations in Australia's rangelands.

Instrinsic variation in the availability of food to animal populations reflects the influence of foraging by the animals themselves. Instrinsic variation in food availability provides a link between population density, subsequent food availability and variation in the rate of population increase (r), operating through density-dependent food shortage. In contrast, extrinsic variation in food availability is caused by environmental influences on food or animal abundance, which are independent of animal foraging. Extrinsic variation in food availability is random relative to that arising through intrinsic shortage. Intrinsic and extrinsic variation in food availability can influence animal populations simultaneously. Intrinsic variation will impart a tendency towards an equilibrium between animal and food abundance. which will be progressively obscured by density-independent variation as the influence of extrinsic factors increases. This study used a large-scale field experiment, in which the density of food-limited feral pig (Sus Scrofa L.) populations was manipulated on six sites, to assess the relative influence of intrinsic and extrinsic variation in food availability. The experiment evaluated the influence of pig population density on r and the abundance of food resources measured as pasture biomass. It was predicted that if intrinsic shortages dominated variation in food availability, pasture biomass and r would decline with increasing pig density. If extrinsic factors dominated variation in food availability, pig density would have no systematic effect on either pasture biomass or r. If intrinsic and extrinsic sources simultaneously affected variation in food availability, higher pig densities would have no systematic effect on r, but would reduce pasture biomass. The simultaneous model predicts reduced pasture biomass because, in the absence of compensatory changes in other sources of variation, the effects of intrinsic and extrinsic factors will be additive. To examine further the degree of interdependence in pig and pasture abundance, a series of stochastic models of the grazing system were estimate and the feedback loop comprising the functional and numerical responses of feral pigs to variation in pasture biomass was manipulated. In the large-scale experiment, neither pasture biomass nor r declined with increasing pig density, suggesting that food availability was dominated by extrinsic factors. However, limitations of the experiment meant that a minor decline in pasture biomass may have gone undetected. Comparison of simulation models, which included and omitted pasture offtake by pigs, indicated that because they were less efficient grazers and persisted at lower average densities relative to other large herbivores, pigs had little influence on variation in pasture biomass.

DNA repair in higher plants

Numerous studies have demonstrated a requirement in plants for repair of DNA damage arising from either intrinsic or extrinsic sources. Investigations also have revealed a capacity for repair types of DNA damage, and conversely, identified mutants apparently defective in such repair. This article provides a concise overview of nuclear DNA repair mechanisms in higher plants, particularly those processes concerned with the repair of UV-induced lesions, and includes surveys of UV-sensitive mutants and genes implicated in DNA repair.

Modeling Pesticide Transport in an Irrigated Field with Variable Water Application and Hydraulic Conductivity

AbstractThe impact of spatially varying hydraulic properties on chemical transport in the unsaturated zone has been extensively studied. However, few studies have investigated the impact of variable water application on chemical transport. This paper uses field data and a modeling study to evaluate the relative importance of intrinsic and extrinsic sources of variability on pesticide transport through a field soil. Saturated hydraulic conductivity represented the source of intrinsic variability and water application was studied as a source of extrinsic variability. A conceptual model of water flow and solute transport was developed based on results from soil cores, shallow groundwater samples, and dye studies. One important result of the field study was the detection of low levels of the applied pesticide metolachlor ([2‐chloro‐N‐(2‐ethyl‐6‐methylphenyl)‐N‐(2‐methoxy‐1‐methyethyl) acetamide]) in groundwater samples collected at 2.6 m below ground surface after an average application of only 0.097 m of water. Dye studies indicated gravity‐driven fingered flow occurred in the subsoil, which may explain the early detection of pesticide in the shallow groundwater. Monte Carlo simulations revealed that the variability of water application had a greater impact on pesticide transport than the variability of saturated hydraulic conductivity at this site. Therefore, improving sprinkler uniformity represents an important best management practice (BMP) for reducing groundwater contamination by agricultural chemicals under the conditions studied.

Pattern of synaptophysin immunoreactivity within mesencephalic grafts following transplantation in a parkinsonian primate model

The majority of investigations into the degree of restoration of neural circuitry following transplantation of the embryonic ventral mesencephalon to the striatum have focused upon the particular neurochemical subtypes of the fibers exchanged between graft and host. Visualization of neurites of specific neurotransmitter type while informative regarding the specificity of graft–host interactions, vastly underrepresents overall synaptogenesis as it may occur in the grafting situation. The present approach of using a molecular marker characteristic of all normal, functional synapses provides broader information about the synaptic remodeling that occurs after tissue grafting. Synaptophysin (SY), an integral membrane protein of the synaptic vesicle, is a reliable marker of nerve terminal differentiation. Immunohistochemical staining with antibodies directed against SY and the dopamine synthetic enzyme tyrosine hydroxylase (TH) was used to assess overall synaptic differentiation as well as the relationship between SY immunoreactivity and the distribution of grafted dopamine (DA) neurons and processes in mesencephalic grafts and mesencephalic-striatal co-grafts implanted in the striatum of MPTP-treated African green monkeys. Grafted embryonic cerebellar tissue was used as a comparison graft type that does not normally exchange prominent direct projections with striatum. Dense pericellular arrays of SY-positive terminals were associated with TH-positive neurons in mesencephalic grafts. In mixed mesencephalic-striatal co-grafts, TH-positive fiber patches within the striatal portion of the graft demonstrated a high degree of correspondence with SY immunoreactivity. In contrast, grafts of cerebellar tissue did not display the same pattern of prominent pericellular arrays of SY staining. These observations suggest that functional synapses are abundantly present within grafted mesencephalon, and that these contacts are enriched in areas of the graft occupied by DA neurons. Implantation of an inappropriate striatal target, the cerebellum, results in visibly diminished innervation. The pattern of SY labeling observed suggests that tissue grafts are extensively innervated, probably both from extrinsic and intrinsic sources, and that the pattern and density of this innervation corresponds to the appropriateness of the graft–host interaction.