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The time course of the development of the sympathetic innervation of the vasculature of the rat tail.

The development of the sympathetic innervation of the tail vasculature in the rat has been examined using catecholamine fluorescence and immunohistochemical techniques to demonstrate tyrosine hydroxylase (TH) and neuropeptide Y (NPY). The tail was found to be largely devoid of noradrenergic terminals at birth. At the earliest ages, axons within nerve trunks and paravascular axon bundles showed high levels of catecholamine fluorescence, but this virtually disappeared as the innervation of the effectors was achieved. The perivascular plexus on the caudal artery was established over the first six postnatal weeks along a rostrocaudal gradient which was retained in the adult, i.e. proximal regions were more densely innervated than distal ones. The innervation of the rest of the vasculature developed relatively late during this period, with the exception of the arteriovenous anastomoses present in the distal half of the tail. These became innervated about 10 days earlier than the adjacent caudal artery at the same levels, and received a much denser innervation in the adult. At all developmental stages, distributions of TH- and NPY-immunoreactive nerve fibres were identical to those seen with catecholamine fluorescence. The sequence of development suggests that the different vascular targets are innervated by subsets of sympathetic neurons having the same neurochemistry but developing independently.

Animals↗

Fate of the multiple innervation of cerebellar Purkinje cells by climbing fibers in immature control, x-irradiated and hypothyroid rats.

The fate of the multiple innervation of Purkinje cells (PCs) by climbing fibers (CFs) was studied as a function of age in immature rats rendered agranular by X-irradiation, in immature hypothyroid rats, and compared to that in controls. This was done by examining in each group the intracellular activities of PCs mediated via CFs throughout maturation. From the third day in control rats, CF responses of PCs evoked by juxta fastigial region (JF) stimulation or occurring spontaneously already resembled the adult responses with, however, some important differences: (1) most of these responses were graded by steps with the intensity of the stimulation before day 13, due to the multiple innervation of PCs by CFs (see below); (2) immature CF responses exhibited a longer duration and their initial spike started near the peak of the EPSP instead of near the baseline later on. Finally, an anlage of CF response was already present in most PCs on day 2, and consisted of a single fast spike elicited near the peak of an underlying all-or-none EPSP. In the 3 groups of rats, CF EPSPs already closely resembled the adult ones as early as 3 days, although their total duration and especially their time to peak were longer. In control rats, these CF EPSPs reversed with depolarizing currents from day 3 and currents for reversal were much lower than in the adult. 'Dual' CF EPSPs of PCS37 were encountered in immature 7- to 10-day-old controls, and persisted in hypothyroid rats until the end of the third postnatal week. The mono- or the multiple innervation of PCs by CFs was ascertained in th 3 groups according to the graded or the all-or-none character of CF EPSPs, and the number of CFs impinging on a given PC was estimated by the number of steps in the response. In control rats, most of PCs were already multiply innervated by CFs as early as 3 days. The multiple innervation culminated on day 5 with an average number of 3.4 CFs for PC, and rapidly regressed later on, so that the adult-type monoinnervation was the rule after day 13. In hypothyroid rats, the establishment of the redundancy and its regression was delayed by 2--3 days. In X-irradiated rats, the settlement and the involution of the multiple innervation of PCs by CFs was exactly superimposed with that seen in controls until day 8. Later on, regression of the supernumerary contacts no longer occurred so that most PCs remained multiply innervated until adulthood. Finally, the first clear-cut IPSPs were detected in PCs on day 9 in control and X-irradiated rats and 2--3 days later in hypothyroid animals.

Aging↗

Peripheral innervation of Opsanus tao (oyster toadfish).

Dual innervation, two morphologically distinct axons ending on the same endplate of white muscle, has been observed in some 'primitive' fish but not 'higher' teleosts. A representative of the order Bachtrachoidiformes, Opsanus tao, was examined using histological sectioning and silver impregnation to determine the innervation of its white muscle. The results demonstrate for the first time, dual innervation in the distributed pattern (innervation along the entire length of the white muscle fibers) in a 'higher' teleost. This indicates that Opsanus tao may represent a species of 'higher' teleosts that has either retained its ancestral mode of innervation (dual innervation) while exhibiting the derived distributed pattern or convergently evolved mode and pattern of innervation.

Animals↗

An anatomical study of cholinergic innervation in rat cerebral cortex.

The cholinergic innervation of rat cerebral cortex was studied by immunohistochemical localization of choline acetyltransferase. Stained bipolar cells, fibers and terminals were found in all areas of cortex. The density of cholinergic terminals was similar in all cortical areas with the exception of entorhinal and olfactory cortex, which showed a marked increase in the number of stained terminals. A laminar distribution of cholinergic terminals was found in many cortical areas. In motor and most sensory areas, terminal density was high in layer 1 and upper layer 5, and lowest in layer 4. Visual cortex, in contrast to other cortical areas, was characterized by a dense band of innervation in layer 4. It has been known that the majority of cortical cholinergic structures derive from a projection to cortex from large, multipolar neurons in the basal forebrain, which stain heavily for choline acetyltransferase. In this study, stained fibers were observed to take three different pathways from basal forebrain to cortex. The first, confined to medial aspects of forebrain and cortex, was observed to originate in the septal area, from where fibers formed a discrete bundle, swinging forward around the rostral end of the corpus callosum, then travelling caudally in the cingulate bundle. The second was found to consist of fibers fanning out laterally from the area of the globus pallidus, travelling through the caudate, then continuing for various distances in the corpus callosum before finally turning into the cortex. A third pathway appeared to innervate olfactory and entorhinal cortex. Ibotenic acid injections were made in the area of the globus pallidus to study the effect of lesioning the lateral pathway on the cholinergic innervation in cortex. A major loss of choline acetyltransferase positive terminals was observed in neocortex, but retrosplenial, cingulate, entorhinal and olfactory cortex showed a normal density of cholinergic innervation. The borders separating areas with lesioned cholinergic input from non-lesioned areas were precise. The distribution of stained terminals remaining in cortical areas with lesioned basal forebrain innervation suggests that the basal forebrain projection to cerebral cortex, and not the intrinsic cortical cholinergic neurons, give rise to the laminar distribution of cholinergic terminals observed in normal cortex. To compare the relative densities of different cholinergic cortical systems, the distribution of choline acetyltransferase staining was compared with that of vasoactive intestinal polypeptide and substance P, which are co-localized in some choline acetyltransferase-positive neurons innervating cortex.

Animals↗

Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior.

The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data provide evidence for an interdependence in the oxidative capacity between a motoneuron and its target muscle fibres in two subpopulations of motoneurons from the same motor pool, i.e. the same muscle.

Animals↗

The autonomic innervation of Rana ridibunda intestine.

1. The innervation of Rana ridibunda intestine has been studied by the following methods: (a) demonstration of cholinesterase activity; (b) FIF method for catecholamines; (c) immunohistochemistry for VIP, SP and SOM, and (d) conventional electron microscopy. 2. The intrinsic intestinal innervation is represented by cholinergic-, VIPergic-, SP- and SOM-like plexuses. The intestinal adrenergic component is of extrinsic origin. 3. The intestinal peptidergic innervation is the most developed, the large intestine being the portion where the studied peptidergic plexuses are more widely distributed. 4. Against a poorly developed cholinergic/adrenergic innervation, it seems that there is a predominant peptidergic innervation in the amphibians intestine wall. 5. Taking into account that amphibians sacral parasympathetic as well as sympathetic innervation development are limited, it could be considered that in vertebrates the intestinal peptidergic innervation is phylogenetically earlier and hence better developed.

Adrenergic Fibers↗

Acetylcholine innervation of sensory and motor neocortical areas in adult cat: a choline acetyltransferase immunohistochemical study.

Light microscopic choline acetyltransferase (ChAT) immunocytochemistry was used to examine the distribution of the acetylcholine innervation in primary motor (4 gamma) and sensory (3a, 3b, 41 and 17) cortical areas of adult cat. In every area, scattered immuno-reactive cell bodies were present and a relatively dense meshwork of ChAT immunoreactive axons pervaded the whole cortical thickness. These axons were generally thin and bore innumerable varicosities of different sizes. A few thicker and smoother fibers and occasional clusters of unusually large varicosities were also visible. Overall, area 17 was less densely innervated than the other areas. In each area, layer I showed the densest innervation. Innervation of underlying layers was rather uniform in area 17, but patterned in other areas. In areas 4 gamma and 3a, layers II, upper III and V showed preferential innervation. Innervation of layer IV was the strongest in areas 3b and 41. Area 3a was transitional between 4 gamma and 3b. Except in area 17, the laminar pattern of acetylcholinesterase staining was consistent with that of ChAT. In the light of current data on the distribution of this cortical innervation in different species, and of its presumed ultrastructural features, it appears likely that such regional and laminar features subtend widespread, modulatory roles of ACh.

Acetylcholine↗

Pattern of corticostriatal innervation in organotypic cocultures is dependent on the age of the cortical tissue.

The patch-matrix organization of the striatum is defined by the selective expression of neuronal markers and a semisegregated pattern of afferents and efferents that develops before birth in all mammals. Differential projections from 'limbic' and 'somatomotor' cortices contribute to the selective circuitry of patch ("striosome") and matrix compartments. Organotypic cultures were used to determine the pattern of early corticostriatal innervation as a first step toward understanding the role of cortical innervation in the development of striatal patch-matrix organization. Perinatal striatum (E19-P4) was cocultured with the cortex obtained from same-age or different-age rats in the presence or absence of substantia nigra obtained from E14-15 fetuses. After 4-21 days in vitro, crystals of biocytin were placed directly onto the cortical piece to trace cortical projections into the striatal piece. Cortex obtained from fetuses (E19-22) or neonatal (P0-1) rats gave rise to a dense innervation of both prenatal and postnatal striatal slices; however, the pattern of biocytin-labeled fibers was found to be highly dependent on the age of the cortical tissue used. Cortex derived from rats between E20 and P1 gave rise to a heterogeneous distribution of fibers indicative of striatal patches when combined with striatal slices from same-age or younger (E18-19) fetuses. Cortex from E18-19 fetuses produced a homogeneous innervation even when cocultured with older striatal tissue in which the striatal patches were already present. The postnatal cortex (P2-P5) gave rise to little to no innervation of striatum of all ages. Similar findings were obtained with the use of either prelimbic or somatosensory cortex. In double- and triple-labeled cultures, the distribution of corticostriatal fibers overlapped substantially with patches of developing striatal neurons, as revealed by DARPP-32 immunocytochemistry. Dopaminergic innervation present when the substantia nigra was included in the cocultures also distributed preferentially to the developing patch compartment, but it did not substantially alter the pattern of corticostriatal innervation. These findings suggest that the cortex provides directive signals to the developing striatum rather than simply responding to the presence of patches that have already formed.

Afferent Pathways↗

Modulation of muscle spindle innervation by neurotrophin-3 following nerve injury.

Muscle spindles monitor changes in muscle length and are innervated by groups Ia and II sensory axons as well as gamma motor axons. Ia sensory axons respond to neurotrophin-3 (NT-3), which plays an important role in sculpting proprioceptive development. Previously, transgenic mice were generated that overexpress NT-3 in muscle (mlc/NT-3 mice). These mice have alterations in proprioceptive elements due to the developmental actions of NT-3 and neuroprotective effects on Ia axons following nerve injury (Taylor, M.D., Vancura, R., Williams, J.M., Riekhof, J.T., Taylor, B.K., Wright, D.E., 2001. Overexpression of neurotrophin-3 in skeletal muscle alters normal and injury-induced limb control. Somatosens. Motor Res. 18 (4), 286-294.) Here, we investigated the actions of NT-3 on each class of injured axons innervating spindles and explored the mechanisms by which NT-3 acts. Immunohistochemical assessment of muscle spindle innervation following crush revealed that the degeneration of Ia axons innervating spindles in mlc/NT-3 mice was substantially reduced, and overall spindle innervation by group II and gamma fibers was greatly improved at later stages. Mlc/NT-3 mice also displayed a significant reduction in the expression of the injury-induced transcription factor ATF3 by retrogradely labeled muscle afferent neurons. The effects of transgenic NT-3 overexpression on spindle innervation could be mimicked if wild-type mice were treated intramuscularly with recombinant NT-3 prior to but not following injury, suggesting that NT-3's actions were due to preexposure to NT-3. This view was supported by in vitro experiments in which large DRG neurons from mlc/NT-3 mice grew significantly longer neurites than wild-type neurons. The results reveal that improved Ia-spindle interactions after injury may enhance spindle innervation by group II and gamma fibers. Finally, exposure of muscle afferent fibers to NT-3 prior to injury alters axonal responses both in vitro and in vivo.

Animals↗

P2X3-immunoreactive primary sensory neurons innervating lumbar intervertebral disc in rats.

The P2X(3) receptor is normally localized in a sub-population of small-diameter dorsal root ganglion (DRG) neurons, and is thought to be related to pain perception. The aim of this study in rats was to examine P2X(3)-immunoreactivity in DRG neurons innervating the lumbar disc and in DRG neurons innervating cutaneous tissues. Fluoro-Gold was applied to the L5-L6 disc, the plantar skin of the hind paw (L4-L5 dermatomes), and the back skin (L1-L2 dermatomes). It has been reported that the L5-L6 disc is innervated by T13-L5 DRG neurons. We performed immunostaining using antibodies against the P2X(3) receptor of T13-L5 DRGs to examine the L5-L6 disc, L4 and L5 DRGs to examine plantar skin and L1 and L2 DRGs to examine back skin. The P2X(3)-immunoreactivity was detected in 22.0 and 22.8% of neurons, labeled by Fluoro-Gold applied to plantar and back skin, respectively. However, P2X(3)-immunoreactivity was detected in only 4.0% of the neurons projecting to the L5-L6 disc. The proportion of P2X(3)-immunoreactive neurons was significantly larger in the DRG neurons innervating the plantar or the back skin, than in the DRG neurons innervating the lumbar disc. These results suggest that the P2X(3) receptors are abundant in DRG neurons innervating cutaneous tissues, but not in neurons innervating the lumbar disc. It is likely therefore that the P2X(3) receptor is less related to the mechanism of discogenic pain, than to cutaneous tissue pain.

Animals↗

Age-related changes of the noradrenergic innervation of rat tracheo-bronchial tree and pulmonary vasculature.

Age-related changes of the noradrenergic innervation of the tracheo-bronchial tree and of pulmonary vasculature were investigated in male Wistar rats of 3 months (young), 12 months (adult) and 24 months (old/aged), using catecholamine histofluorescence techniques associated with image analysis and by high pressure liquid chromagraphy with electrochemical detection. In young rats, blue-green fluorescent nerve fibres supply tracheo-bronchial smooth muscle and tracheal and bronchial glands, which are innervated by a delicate network of nerve fibres rich in varicosities. Pulmonary artery and vein are sparsely innervated. They are supplied with nerve fibres distributed in the vasa vasorum or the adventitia and the outer tunica media. The higher noradrenaline concentrations were found in the trachea and extraparenchymal bronchi, followed by pulmonary vein and pulmonary artery. The density and pattern of noradrenergic innervation of the tracheo-bronchial tree, or of the pulmonary vasculature, were similar in young and adult rats. In aged rats, a loss of noradrenergic innervation involving primarily the supply to the smooth muscle of the tracheo-bronchial tree was observed. Histofluorescence techniques demonstrated a higher sensitivity than noradrenaline assay in detecting changes of the sympathetic innervation of the tracheo-bronchial tree and of the pulmonary vasculature. The possible significance of reduced noradrenergic innervation of the tracheo-bronchial tree in aged rats is discussed.

Adrenergic alpha-Agonists↗

Regeneration of implanted splenic tissue in the rat: re-innervation is host age-dependent and necessary for tissue development.

The loss of spleen may lead to fatal bacterial infections. To prevent this, splenic autotransplantation has been performed in humans and experimental animals. However, there is still controversy about the protective function of this procedure. Since innervation plays an important role in splenic function, we investigated whether splenic regenerates are re-innervated, and whether this depends on the donor and host age. Splenic tissue (30 mg) was implanted into the greater omentum of either young (2 days) or old (12 months) rats, from either young or old syngeneic animals. After 3 months of regeneration, the weight of the regenerates was determined, PGP+ nerve fibers were revealed by immunohistology, and subdivided into nerve fibers of sympathetic (TH+, NPY+) or sensory (SP+, CGRP+) origin. In addition, proliferating (Ki-67 proliferation antigen+) and apoptotic cells (TUNEL technique+) were likewise investigated. No innervation of splenic regenerates was observed after implantation into old hosts, correlating with poorly developed splenic compartments. In contrast, almost normal re-innervation occurred in young hosts after implantation of both young and old splenic tissue. These regenerates showed well-developed splenic compartments and a normal number and tissue distribution of proliferating and apoptotic cells. However, after the implantation of young tissue, the final size of splenic regenerates was three times larger (140 +/- 30 vs. 40 +/- 10 mg). Thus, re-innervation of splenic implants is necessary for their subsequent development. It is determined by host age, whereas the final size of the splenic regenerates is regulated by donor age-dependent factors. This model is useful for studying both the process leading to initial innervation and the consequences of this innervation.

Aging↗

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

The electrophysiological properties of the normal brachial plexus and functional motor innervation were examined during the operation of transfer of contralateral C7 transfer from the healthy side. Different roots of the brachial plexus were stimulated and maximum amplitudes were recorded. The results showed that functional motor innervation of brachial plexus roots were: C5 mainly forms the axillary nerve to innervate the deltoid muscle; C6 mainly forms the musculocutaneous nerve to innervate biceps; C7 mainly forms the radial nerve to innervate triceps; C8 mainly forms the median nerve to innervate flexor digitorum superficialis and profundus; and T1 mainly forms the ulnar nerve to innervate the intrinsic muscles of the hand.

Adult↗

Evidence for nodose ganglion as the source of innervation to the anterior lobe of the pituitary gland.

Recent studies have provided convincing evidence for the presence of peptidergic nerve fibers in the pituitary anterior lobe in several animal species. This study was aimed at elucidating the origin of this innervation by neuroanatomical tracing, denervation experiments, and immunohistochemistry. Immunohistochemistry against substance P and growth-associated protein 43 revealed a dense fiber plexus within the anterior lobe, and these markers were mostly colocalized. Retrograde tracing with Fluorogold from the pituitary gland stained neurons in the hypothalamus, superior cervical ganglia and the nodose ganglia. None of the Fluorogold-labelled neurons in the hypothalamus or superior cervical ganglion were substance P-immunoreactive, while many of the neuronal cell bodies in the nodose ganglion exhibited substance P immunoreactivity. There were no Fluorogold-labelled neurons in the trigeminal, otic or cervical dorsal root ganglia. Surgical transection of the pituitary stalk or bilateral removal of the superior cervical ganglion did not abolish the anterior lobe nerve fibers, and anterograde tracing with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine perchlorate from the pituitary stalk failed to stain any nerve fibers within the anterior lobe. Our findings suggest that the nodose ganglion neurons likely innervate the pituitary anterior lobe, while neither hypothalamus nor sympathetic superior cervical ganglion may be a source of this innervation. By showing a distinct neuronal system in the pituitary anterior lobe our findings (i) support the previous functional studies demonstrating a distinct regulation of the morphology of the anterior lobe innervation by hormonal changes, and (ii) suggest that the innervation of the pituitary anterior lobe is a part of the visceral innervation by the vagus nerve rather than a part of the other intracranial innervation. These findings provide a neuroanatomic basis for the reported observations about the neural regulation of the pituitary anterior lobe.

Animals↗

Neurokinin-1 and neurokinin-3 receptors are expressed in vagal efferent neurons that innervate different parts of the gastro-intestinal tract.

Vagal efferent neurons innervating the digestive tract are mainly contained in the dorsal motor nucleus of the vagus. Previous studies have suggested that neurokinins and their neurokinin-1 and neurokinin-3 receptors are involved in the parasympathetic control of digestive functions. The purpose of the present study was to analyze the distribution of neurokinin-1 and neurokinin-3 receptors amongst vagal efferent neurons innervating the stomach, the duodenum, the ileum and the cecum. The immunocytochemical detection of neurokinin-1 and neurokinin-3 receptors was combined with the immunocytochemical detection of retrogradely transported cholera toxin-B subunit, previously injected in the gut wall. Neurokinin-1 and neurokinin-3 receptors were present in 19+/-7% and 8+/-3% of retrogradely labeled neurons innervating the stomach. Almost half of the labeled neurons innervating the duodenum (46+/-7%) expressed neurokinin-1 receptors but less than 0.5% contained neurokinin-3 receptors. None of the retrogradely labeled vagal efferent neurons innervating the ileum and the cecum were immunoreactive for neurokinin-1 and neurokinin-3 receptors. We conclude that neurokinin-1 and neurokinin-3 receptors are located on vagal efferent neurons which innervate the stomach and that neurokinin-1 receptors are common, whereas neurokinin-3 receptors are rare on neurons projecting to the duodenum. Additionally, the distal part of the rat small intestine is innervated by vagal efferent neurons that do not express neurokinins receptors on their membrane. This suggests that neurokinins may influence the parasympathetic control of different regions of the gastro-intestinal tract in specific ways.

Animals↗

Muscle activity-resistant acetylcholine receptor accumulation is induced in places of former motor endplates in ectopically innervated regenerating rat muscles.

Expression of acetylcholine receptors (AChRs) in the extrajunctional muscle regions, but not in the neuromuscular junctions, is repressed by propagated electric activity in muscle fibers. During regeneration, subsynaptic-like specializations accumulating AChRs are induced in new myotubes by agrin attached to the synaptic basal lamina at the places of former motor endplates even in the absence of innervation. We examined whether AChRs still accumulated at these places when the regenerating muscles were ectopically innervated and the former synaptic places became extrajunctional. Rat soleus muscles were injured by bupivacaine and ischemia to produce complete myofiber degeneration. The soleus muscle nerve was permanently severed and the muscle was ectopically innervated by the peroneal nerve a few millimeters away from the former junctional region. After 4 weeks of regeneration, the muscles contracted upon nerve stimulation, showed little atrophy and the cross-section areas of their fibers were completely above the range in non-innervated regenerating muscles, indicating successful innervation. Subsynaptic-like specializations in the former junctional region still accumulated AChRs (and acetylcholinesterase) although no motor nerve endings were observed in their vicinity and the cross-section area of their fibers clearly demonstrated that they were ectopically innervated. We conclude that the expression of AChRs at the places of the former neuromuscular junctions in the ectopically innervated regenerated soleus muscles is activity-independent.

Acetylcholinesterase↗

Spatial geometry of the dopamine innervation in the avascular area of the human fovea.

The dopamine (DA) innervation, labeled by tyrosine hydroxylase immunohistochemistry in a wholemounted human retina, is described in the avascular area of the fovea. Eleven DA neurons give rise to this innervation, among which five are interplexiform cells, so that the DA innervation consists of two plexuses: one is internal and is formed by the dendrites of all of the DA cells, and the other is external and is formed by the scleral processes of the interplexiform cells. Five concentric zones are delineated according to the focal plane in which the internal DA plexus is observed. The central zone 1 contains DA processes crossing in all directions. Zones 2 and 3 do not contain any cell bodies. In zone 3 the internal plexus begins to undergo a concentric arrangement, which is clearly observed in zones 4 and 5. The external DA innervation displays a different appearance in zones 1, 2, and 3, in which it consists of vertically oriented thin processes and terminals penetrating the outer nuclear layer, vs. zones 4 and 5 in which it consists of both the same type and horizontal processes lying in the outer plexiform layer. On the basis of DA-innervation appearance and distribution of labeled and unlabeled cell somata, it was concluded that zones 1, 2, and 3 contained the DA innervation of the foveola. DA processes filtering between photoreceptor cells are particularly well-observed in this region. This anatomical study of the DA innervation in the human fovea leads to a better understanding of the important role of DA in primate central vision and can be used as a reference for an approach of macular pathology.

Aged↗

Multiple innervation of tonic endplates revealed by activity-dependent uptake of fluorescent probes.

During development of the vertebrate nervous system, there is a widespread reduction in the number of axons innervating target cells. This phenomenon, often called synapse elimination, has been particularly well studied at the neuromuscular junction of developing twitch muscle fibres: following a period of polyneuronal innervation, axonal branches are retracted, usually leaving each twitch fibre endplate innervated by only one axon. Here we describe a new technique for the study of synapse elimination--activity-mediated uptake of fluorescent probes. These probes selectively and supravitally label all the terminals of individual axons. The technique is used here in adult and embryonic snakes to study the innervation pattern of a thin muscle containing two fibre types: twitch fibres, which are fast-contracting and have propagated action potentials, and tonic fibres, which are slow-contracting and lack action potentials. We find that twitch muscle fibres, as expected, eliminate all polyneuronal innervation during development; in contrast, tonic fibre endplates remain polyneuronally innervated into adulthood. The persistence of multiple innervation at tonic endplates may be related to the lack of action potential activity in tonic muscle fibres.

Action Potentials↗