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PubMed2001

Calcium channels coupled to neurotransmitter release at dually innervated neuromuscular junctions in the newborn rat.

We studied the effect of several calcium channel blockers (omega-Conotoxin-GVIA, 1 and 3microM; omega-Agatoxin-IVA, 100nM; Nitrendipine, 1 and 10microM) on evoked transmitter release at singly and dually innervated endplates of the levator auris longus muscle from three- to six-day-old rats. In dually innervated fibers, a second endplate potential may appear after the first one when we increase the stimulation intensity. The lowest and highest endplate potential amplitudes are designated "small endplate potential" and "large endplate potential", respectively. The percentage of doubly innervated junctions remains almost constant throughout the age range examined. Nevertheless, the percentage of junctions innervated by three or more terminal axons drops, whereas the singly innervated junctions increase. Therefore, between postnatal days 3 and 6, roughly half the neuromuscular junctions may experience the final process of axonal elimination. The synaptic efficacy of the large endplate potential in dual junctions, measured as the mean amplitude of the synaptic potential and mean quantal content, was the same as in the junctions that had become recently mono-innervated in the same postnatal period. In singly innervated fibers, the endplate potential size was strongly reduced by both the P/Q-type voltage-dependent calcium channel blocker omega-Agatoxin-IVA (79.17+/-4.02%; P < 0.05) and the N-type voltage-dependent calcium channel blocker omega-Conotoxin-GVIA (56.31+/-7.80%; P < 0.05), whereas endplate potential amplitude was not significantly changed by the L-type voltage-dependent calcium channel blocker Nitrendipine. In dually innervated fibers, the P/Q-type voltage-dependent calcium channel blocker omega-Agatoxin-IVA and L-type voltage-dependent calcium channel blocker Nitrendipine increased the size of the small endplate potential (161.29+/-47.87% and 109.32+/-11.03%, respectively; P < 0.05 in both cases) and reduced the large endplate potential (74.42+/-15.32% and 70.91+/-10.04%, respectively; P < 0.05 in both cases). The N-type voltage-dependent calcium channel blocker omega-Conotoxin-GVIA significantly increased the small endplate potential in the first few minutes after toxin application (at 10min: 90.23+/-17.38%; P < 0.05). This increase was not maintained, while the large endplate potential was strongly inhibited (69.25+/-7.5%; P < 0.05). In conclusion, in the dually innervated endplates of the newborn rat, presynaptic calcium channel types can have different roles in transmitter release from each of the two inputs, which suggests that nerve terminal voltage-dependent calcium channels are involved in neonatal synaptic maturation.

Aging↗
PubMed1997

Regression of polyneural innervation in the human psoas muscle.

During the early stages of mammalian ontogeny muscle fibres are innervated by more than one axon. This polyneural innervation is replaced by mononeural innervation in the course of development. The regression of polyneural innervation in the psoas muscle in the human is the topic of the present study. Innervation patterns were studied in fetuses from 15 1/2 weeks of post menstrual age (PMA) and in babies until 80 weeks PMA (40 weeks after term age) and compared to data from two adults. Motor endplates were stained by a combined acetylcholinesterase stain. Innervation patterns and motor endplate morphology were studied and the sizes of endplates were measured. As a main result of our study polyneural innervation of the psoas muscle remains at a level of about 2 endings per endplate (range 1-5 terminals) until 18-25 weeks PMA and decreases thereafter. From 52 weeks PMA (12 weeks post term) onwards, muscle fibres are predominantly mononeurally innervated. During development the morphology of the terminal patterns of the nerve endings becomes more complex and the size of endplates increases, implying that the adult pattern of muscle innervation is reached at the age at which a major functional transformation in the neurobehavioural repertoire occurs (i.e. the end of the second and the beginning of the third month.

Acetylcholinesterase↗
PubMed2005

The innervated anterolateral thigh flap: anatomical study and clinical implications.

During the past 20 years, the neural anatomy of many flaps has been investigated, although no extensive studies have been reported yet on the anterolateral thigh flap. The goal of this study was to describe the sensory territories of the nerves supplying the anterolateral thigh flap with dissections on fresh cadavers and with local anesthetic injections in living subjects. The sensate anterolateral thigh flap is typically described as innervated by the lateral cutaneous femoral nerve. Two other well-known nerves, the superior perforator nerve and the median perforator nerve, which enter the flap at its medial border, might have a role in anterolateral thigh flap innervation. Twenty-nine anterolateral thigh flaps were elevated in 15 cadavers, and the lateral cutaneous femoral nerve, the superior perforator nerve, and median perforator nerve were dissected. In the injection study, the lateral cutaneous femoral nerve, superior perforator nerve, and median perforator nerve in 16 thighs of eight subjects were sequentially blocked. The resulting sensory deficit from each injection was mapped on the skin and superimposed on the marked anterolateral thigh flap territory. The study shows that the sensate anterolateral thigh flap is basically innervated by all three nerves. The lateral cutaneous femoral nerve was present in 29 of 29 thighs, whereas the superior perforator nerve was present in 25 of 29 and the median perforator nerve in 24 of 29 thighs. Furthermore, in the proximal half of the flap, the lateral cutaneous femoral nerve lies deep, whereas the superior perforator nerve and median perforator nerve lie more superficially. Whereas the lateral cutaneous femoral nerve innervates the entire flap, the superior perforator nerve innervates 25 percent of the flap and the median perforator nerve innervates 60 percent of the flap. Clinically, a small anterolateral thigh flap (7 x 5 cm) can be raised sparing the lateral cutaneous femoral nerve and using only the selective areas innervated by the superior perforator and median perforator nerves. Alternatively, a large anterolateral thigh flap can be raised with this multiple innervation. This can be helpful if one wants to harvest the flap under local anesthesia. Sensate bilobed flaps can be harvested when dual innervated flaps are required.

Cadaver↗
PubMed1971

Noradrenaline uptake by non-innervated smooth muscle.

1. Uptake of noradrenaline (NA) into the non-innervated smooth muscle cells of the human umbilical artery and the chick amnion has been studied with the fluorescence histochemical technique for localizing monoamines. Comparison has been made with uptake into sympathetically innervated smooth muscle of the rabbit ear artery.2. Accumulation of NA within non-innervated smooth muscle cells is observed histochemically after exposure to much lower concentrations of NA (10(-7) g/ml) than in sympathetically innervated smooth muscle cells, where accumulation occurs with NA (10(-5) g/ml).3. In contrast to innervated smooth muscle, uptake of NA (10(-4) g/ml) by non-innervated smooth muscle is characterized by lack of inhibition by phenoxybenzamine, normetanephrine and cold, although some inhibition is apparent at lower NA concentrations. Retention of NA during prolonged washing in NA-free Krebs demonstrates that it is strongly bound within the non-innervated smooth muscle cells, particularly in the nucleus.4. After inhibition of catechol-O-methyl transferase, the accumulation of NA in innervated smooth muscle closely resembles that in non-innervated smooth muscle.

Amnion↗
PubMed1982

Short- and long-term effects of paralysis on the motor innervation of two different neonatal mouse muscles.

1. A study was made of short- and long-term effects of paralysis induced by type A botulinum toxin on the development of innervation of mouse muscles. The toxin was injected locally over the tensor fasciae latae (t.f.l.) and gluteus muscles at various times after birth, and the innervation was later examined by intracellular recording and by a histological technique using a reduced silver stain for axons.2. Paralysis induced at 0-4 days of age delayed but did not prevent the eventual elimination of nearly all focal multiple innervation in gluteus muscle fibres, whereas in t.f.l. up to 50% of the fibres remained focally innervated by more than one axon for at least 120 days. There was an associated reduction in the number of muscle fibres in t.f.l. of between 50 and 70%. The biggest reduction in the number of gluteus fibres was under 40%.3. In the t.f.l., paralysis begun at 6-9 days caused the extent of single-site polyneuronal innervation to increase above the level existing at the time of paralysis. Histologically this increase was seen to be due at least in part to the stimulation of nodal sprout growth from a limited number of nodes.4. Motor nerve terminal sprouts were evoked by paralysis at all ages. In mice injected before 4 days of age recovery from the toxin occurred rapidly and without the formation of ectopic synapses by sprouted motor terminals; however, intrafusal motor nerves also sprouted and established a permanent ectopic innervation on surrounding extrafusal muscle fibres.5. The following conclusions are drawn. (a) In some but not all muscles, neonatally induced paralysis can not only temporarily halt elimination of polyneuronal innervation but actually lead to an increase; it is suggested tentatively that this occurs only during the neonatal period because of the availability at that time of endoneurial pathways associated with normal polyneuronal innervation, rather than because of any special neuronal growth potential then. (b) Permanent establishment of focal polyneuronal innervation is due not to stability of presynaptic elements maintained past a critical developmental stage but is associated with substantial losses of muscle fibres, leading to a high ratio of nerve fibres to muscle fibres.

Aging↗
PubMed1986

Increase in polyneuronal innervation in frog muscle after muscle injury.

The proportion of polyneuronal innervation was evaluated electrophysiologically in curare-blocked frog cutaneous pectoris muscles after local injury to the muscle fibres on one side. Focal polyneuronal innervation was revealed by recording end-plate potentials evoked by a gradual increase in the stimulus intensity applied to the motor nerve. An increase in the proportion of focally polyneuronally innervated muscle fibres appeared in the injured muscle 3-5 days after injury. The difference between the values obtained 3-5 days and 7-9 days (31 and 38%, respectively) and the control value (18%) was highly significant. A similar increase in the proportion of pluri-innervated muscle fibres was observed in the contralateral muscle, but after a longer period. The different components of complex end-plate potentials (e.p.p.s) usually had similar latencies and rise times in control and experimental muscles. This may indicate that the axons had similar conduction velocities and that synapses were located close to each other. A repeated muscle fibre section 24 h after the initial injury resulted in an enhanced polyneuronal innervation (52%) 7-9 days after the first section. The experiments were repeated on partially blocked muscles in order to detect small e.p.p.s with an amplitude similar to that of spontaneous miniature end-plate potentials (m.e.p.p.s). The proportion of polyneuronally innervated fibres estimated by this technique in control muscles approximated 40%. Polyneuronal innervation was also found to be significantly increased in cut muscles 7-9 days after muscle injury and a week later in contralateral muscles. Combined silver and cholinesterase staining was used to detect morphologically polyneuronal innervation. The comparison of morphological and electrophysiological data indicated that the increase in polyneuronal innervation after muscle injury is likely due to nerve sprouting and formation of new synapses. The results suggest that the signal for nerve sprouting originates from the damaged muscle cell and that it is transferred transneuronally to the contralateral side.

Action Potentials↗
PubMed1986

Topographical projections of segmental nerves to the frog glutaeus muscle during loss of polyneuronal innervation.

The development of synaptic connexions to the frog (Limnodynastes tasmaniansis) glutaeus muscle from segmental nerves 8 and 9 was determined using glycogen depletion, contraction and electrophysiological methods between stages 54 and 60 (Nieuwkoop & Faber, 1975). There was no change in the number of muscle cells in the glutaeus from stage 55 onwards; the maturation of muscle cells was most advanced at the point of nerve entry on the ventral surface of the glutaeus and least advanced at the dorsal surface. Electrophysiological determination of the segmental innervation of the dorsal surface of the muscle in low calcium (0.5 mM) indicated that the muscle was almost uniquely innervated by nerve 8 at stage 54. Weak nerve 9 terminals were detected at stage 54 only if the calcium concentration was raised to 6.0 mM. Innervation by nerve 9 was first detected in low calcium at stage 55. There was then a progressive decrease in the innervation of the glutaeus muscle by nerve 8 in regions apposed to the iliofibularis muscle, until stage 59 when this part of the glutaeus was almost completely innervated by nerve 9. Glycogen depletion of muscle fibres following tetanic stimulation of either segmental nerve confirmed that the region of the glutaeus muscle apposed by the iliofibularis becomes progressively innervated by nerve 9 during development. Contraction studies of the segmental innervation of the glutaeus muscle in normal calcium (2 mM) indicated that the muscle was predominantly innervated by nerve 8 at stage 54. There was then a progressive increase in the number of nerve 9 motor units up to stage 56. The size of individual motor units declined for both nerves 8 and 9 until stage 59, when the average motor unit size was about 9% of the muscle. It is suggested that the decline in the innervation by nerve 8 of the side of the glutaeus muscle apposing the iliofibularis muscle is due to this region of the muscle selectively favouring synapse formation by nerve 9 over nerve 8.

Animals↗
PubMed1988

Innervation of the thick ascending limb of Henle.

The overlap of accumulations of autoradiographic grains (AAGs) on profiles of the thick ascending limb of Henle (TALH) was measured in autoradiograms of sections from rat kidneys with monoaminergic nerves labeled by means of tritiated norepinephrine. The amount of AAG overlap was used as an indirect means of quantifying innervation along the TALHs of superficial, mid-cortical, and juxtamedullary nephrons. The density of innervation along the TALH showed nephron heterogeneity; the juxtamedullary nephrons with a high pre- and postjuxtaglomerular apparatus (JGA) TALH density of innervation and the upper and midcortical nephrons with high TALH innervation densities at the level of the JGA. The pre-JGA TALH of the juxtamedullary nephrons had a significantly higher (P less than 0.001) density of innervation than the midcortical or superficial nephrons. The TALHs of juxtamedullary nephrons were found to have substantially more innervation than the TALHs of the other nephrons. For all three populations of nephrons, the pre-JGA TALH had the greatest amount of innervation. Neural regulation of TALH function would occur mainly along the pre-JGA and level of the JGA TALH. This regulation would increase TALH NaCl reabsorption (decrease luminal NaCl concentration) and therefore influence 1) the urinary concentrating mechanism, and 2) renin secretion via the macula densa mechanism. The innervation of the TALH was predominantly associated with the vasculature of the TALH's own nephron. However, innervation associated with medullary ray capillary beds from deeper nephrons was observed on pre-JGA TALHs from superficial and midcortical nephrons.

Animals↗
PubMed1999

Sympathetic and sensory innervations are heterogeneously distributed in relation to the blood vessels at the extensor carpi radialis brevis muscle origin of man.

By using immunohistochemistry and antibodies to a general nerve marker, protein gene product (PGP) 9.5, the overall innervation at the extensor carpi radialis brevis (ECRB) muscle origin was investigated in patients with tennis elbow and in healthy controls. The autonomic innervation was studied by using antibodies to neuropeptide Y (NPY), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP). The sensory innervation was visualized by using antibodies to substance P and calcitonin gene-related peptide. PGP 9.5 immunoreactions were detected in association with small blood vessels and arteries and within nerve bundles. There was, however, heterogeneity in the perivascular nerve fiber distribution since some blood vessels exhibited a high degree of PGP 9.5 innervation and some negligible or no such innervation at all. There was marked TH/NPY innervation in the walls of a subpopulation of the arteries, basically no VIP-containing nerves, and sensory innervation restricted to the small blood vessels. These observations show that the ECRB muscle origin is supplied with heterogeneously distributed sympathetic and sensory innervations and, furthermore, that there appears to be an imbalance between the vasoconstrictor and vasodilator innervations along the vascular tree in this region.

Adult↗
PubMed1994

Monoaminergic innervation patterns in the anterior dorsal ventricular ridge of a lacertid lizard, Psammodromus algirus.

In contrast to the view of a diffuse monoaminergic innervation of the telencephalon, studies on the monoaminergic innervation in certain mammalian isocortical regions have shown a high degree of regional and laminar specificity. The present study was designed to examine the distribution patterns of dopamine, noradrenaline and serotonin in a telencephalic structure, the anterior dorsal ventricular ridge, of the sand lizard Psammodromus algirus (Lacertidae) using specific antibodies against each monoamine. The anterior dorsal ventricular ridge receives an abundant monoaminergic innervation compared to that of cortical telencephalic regions. The distribution of the different monoamines presented zonal and regional patterns throughout the ridge. The cell cluster zone was profusely innervated by catecholamines, whereas no serotoninergic fibers innervated the cell bodies in the cluster zone. On the other hand, the periventricular zone was heavily innervated by serotonin, but catecholaminergic fibers were almost lacking. With regard to regional patterns, dopamine exhibited major differences in the mediolateral axis of the anterior dorsal ventricular ridge: dopaminergic innervation was densest in the lateral region, which in other reptiles is described as a target of visual thalamic projections. Whereas the zonal pattern of the monoaminergic innervation of the anterior dorsal ventricular ridge seems to be a constant feature in the reptiles studied to date, the regional pattern varies among reptilian groups, especially taking into account the density of monoaminergic innervation.

Animals↗
PubMed1999

Neurotransmitters and neuromodulators involved in laryngeal innervation.

The distribution and role of neurotransmitters and neuromodulators in laryngeal innervation are reviewed, and our recent findings regarding the nitrergic innervation of the larynx are demonstrated for the better understanding of the complexity of the laryngeal innervation system. Noradrenergic innervation of the larynx was studied with fluorescence histochemistry and electron microscopy after application of 5-hydroxydopamine. These studies confirmed the existence of noradrenergic innervation for the submucosal glands and blood vessels, and the origin and course of noradrenergic nerve fibers contained in the laryngeal nerves and their destinations in the larynx. Cholinergic innervation of the larynx has not been clarified in detail. Many kinds of neuropeptides have been demonstrated to be involved in laryngeal innervation. Vasoactive intestinal polypeptide originating from intralaryngeal ganglionic neurons participates in laryngeal vasodilation and reduction of laryngeal seromucous secretion. Neuropeptide Y nerve fibers are few in the larynx, and most originate from the superior cervical ganglion. They are distributed around the large or medium-sized blood vessels, especially arteries. They are also associated with excretory structures. Substance P was the first neuropeptide found to be a sensory neurotransmitter in the laryngeal afferent system. It is also involved in regulation of laryngeal blood flow and secretion. Calcitonin gene-related peptide is associated with the sensory, autonomic, and motor innervation of the larynx. The majority of enkephalin nerve fibers are located close to excretory structures, although no information on the physiological significance of enkephalin is available. In addition to the above neuropeptides, the peptides histidine isoleucine, histidine methionine, and helospectin have been shown to exist in the larynx. The nitrergic innervation of the larynx has been recently studied with NADPH-diaphorase histochemistry and immunohistochemistry using antiserum against nitric oxide synthase. Nitric oxide originates from the neurons in the intralaryngeal ganglia and is believed to modulate blood flow and secretion of the larynx. It controls the laryngeal exocrine secretion in cooperation with intrinsic vasoactive intestinal polypeptide and/or extrinsic calcitonin gene-related peptide. Nitric oxide from the nodose ganglion may modulate nociception of the larynx. The existence of nitrergic neurons located in the intrinsic laryngeal muscles has been demonstrated. Many of them are bipolar or pseudounipolar, so they might be sensory in nature. The effect of injury of the recurrent laryngeal nerve on the induction of nitric oxide synthase in the laryngeal motoneurons is also discussed.

Acetylcholine↗
PubMedDate not supplied

Morphological and functional evidence for enhanced growth and potassium-evoked dopamine release in striatal grafts innervated with a patchy growth pattern. An in oculo nigrostriatal cograft study.

During development of the nigrostriatal dopamine system, a patchy and a diffuse type of striatal innervation pattern can be seen. It has been suggested that when fetal dopaminergic neurons, obtained from the ventral mesencephalon (VM), are grafted adjacent to mature striatal tissue, only the diffuse growth is induced. Intraocular grafting studies have indicated that the dopaminergic growth pattern might be influenced by the age of the target area, the lateral ganglionic eminence (LGE). In this study VM grafts were allowed to innervate LGE grafts of different ages. Fetal VM was implanted next to 2-wk-old or 26-day-old striatal in oculo grafts, and the resulting dopaminergic innervation of the striatal grafts was studied using tyrosine hydroxylase (TH) immunohistochemistry. In striatal grafts receiving innervation at the age of 2 wk in oculo, a patchy TH-immunoreactive growth pattern was found, while in striatal grafts innervated at the age of 26 days mainly the diffuse growth pattern was seen. This implies that grafted striatum reached maturity at approximately 1 mo of age. The age of the dopaminergic neurons at dissection and grafting was also studied concerning the ability to induce patchy growth into mature striatum. Thus, VM dissected from 13- and 18-mm fetuses was implanted to either 4-mo-old LGE (grafted in sequence) or to LGE from the same fetus (grafted simultaneously) as controls. TH-positive innervation of striatal tissue, evaluated 4 wk after implantation of VM, revealed a patchy growth pattern in LGE grafted simultaneously with 13- and 18-mm VM. However, when the striatum was mature at the time of innervation, diffuse growth was observed in striatum innervated by VM dissected from 13-mm fetuses. Interestingly, patchy growth was noted in striatal areas close to VM grafts when the dopaminergic neurons were derived from older fetuses (CRL 18 mm). Furthermore, potassium-induced dopamine release was greater in striatal grafts exhibiting the patchy growth than those showing the diffuse pattern of innervation. In conclusion, patchy dopaminergic growth can be induced in mature striatal tissue by grafting VM from older fetuses. Functionally, potassium-evoked dopamine release is enhanced in dopaminergic patches. These results have implications in terms of finding ways to induce patchy growth when grafting to the mature striatum of patients suffering from Parkinson's disease.

Animals↗
PubMed1987

The pattern of innervation in serially duplicated axolotl limbs: further evidence for the existence of local pathway cues?

The innervation of the biceps muscle was examined in regenerated and vitamin A-induced serially duplicated axolotl forelimbs using retrograde transport of horseradish peroxidase. The regenerated biceps muscle becomes innervated by motor neurones in the same position in the spinal cord as the normal biceps motor pool. In previous experiments in which the innervation of a second copy of a proximal limb muscle was examined in serially duplicated limbs (Stephens, Holder & Maden, 1985), the duplicate muscle was found to become innervated by motor neurones that would normally have innervated distal muscles. In the present study, the innervation of the second copy of biceps was examined under conditions designed to encourage nerve sprouting from 'correct' biceps axons. Following either partial limb denervation or denervation coupled with removal of the proximal biceps, the second copy of the muscle was still innervated by inappropriate motor neurones, which again would normally innervate distal limb muscles. These results are interpreted as evidence for the necessity for an appropriate local environment for axonal growth to allow reformation of a correct pattern of motor innervation in the regenerated limb.

Ambystoma↗
PubMed1989

Hypernoradrenergic innervation: its relationship to functional and hyperplastic changes in the vasculature of the spontaneously hypertensive rat.

There is now compelling evidence indicating that there is a greater sympathetic innervation of blood vessels in the spontaneously hypertensive rat (SHR) when compared with the innervation of corresponding vessels in the normotensive genetic control rat (WKY). In selected vascular beds in the SHR, increased sympathetic innervation occurs immediately after birth and prior to the expression of hypertension in the animal. In contrast, the available evidence suggests that the sympathetic innervation of cardiac tissue in SHR and WKY are similar in young and adult rats. The functional significance of the enhanced sympathetic innervation of blood vessels in the SHR with regard to the development or maintenance of hypertension relates in two ways to the well-established phenomena of vascular smooth muscle cell hypertrophy and hyperplasia, which are thought to be the pathophysiological basis for the increased peripheral vascular resistance and elevated blood pressure in this animal model of hypertension. First, the enhanced innervation of blood vessels in the SHR leads to an augmented release of the vasoconstrictor transmitter noradrenaline (NA). The predicted consequences of this augmented release of NA upon vascular contraction are modulated by the presence of a larger number of sites for neuronal inactivation (i.e. reuptake sites) of NA by virtue of the presence of the increased innervation. Second, and of more significance, is the inter-relationship between hypernoradrenergic innervation and vascular smooth muscle hyperplasia, as the early appearance of such changes is a powerful indicator for the subsequent expression of hypertension in the SHR. In view of the substantial evidence that implicates vascular smooth muscle cells in regulating the degree of their sympathetic innervation and confirms the influence of sympathetic nerves upon vascular smooth muscle hyperplastic change, attention is drawn to the role of trophic factors in providing the setting for the development of hypertension in the SHR.

Animals↗
PubMedDate not supplied

[Functional characteristics of Rana temporaria arteries and veins with different densities and neuromediator properties of vasomotor innervation].

Pharmacological studies have been made of frog's arteries and veins with different density and transmitter nature of their vasomotor innervation. It was found that the difference in vasomotor innervation of the blood vessels is related to the level of their maximal contractile response. The higher the adrenergic innervation, the higher the response to exogeneous catecholamines. The higher the cholinergic innervation, the higher the response to acetylcholine. Vasomotor innervation affects the sensitivity of the blood vessels, however catecholamine sensitivity is also observed in non-innervated vascular smooth muscle cells. alpha-Adrenoreceptors were found both in the innervated and non-innervated vessels, whereas beta-adrenoreceptors are present only in the innervated ones.

Adrenergic Fibers↗
PubMed1984

Postnatal development of laminar innervation patterns by monoaminergic fibers in monkey (Macaca fascicularis) primary visual cortex.

Immunohistochemical methods are used to characterize the distribution of noradrenergic and serotonergic fibers in primary visual cortex of cynomolgus monkeys (Macaca fascicularis) at various postnatal ages. Previous studies in adult squirrel monkeys have shown that serotonergic fibers are generally restricted to the upper four cortical laminae and are especially dense in layer IV, whereas noradrenergic fibers are especially dense in layers V and VI, moderate in layers I, II, and III, and virtually absent in layer IV (Morrison, J. H., S. L. Foote, M. E. Molliver, F. E. Bloom, and H. G. W. Lidov (1982) Proc. Natl. Acad. Sci. U.S.A. 2401-2405; Morrison, J. H., S. L. Foote, D. O'Connor, and F. E. Bloom (1982) Brain Res. Bull. 9: 309-319). Since these monoamines, especially norepinephrine, have been hypothesized to play an essential role in the developmental plasticity of visual cortex organization (e.g., Kasamatsu, T., and J. D. Pettigrew (1976) Science 194: 206-209; Pettigrew, J. D., and T. Kasamatsu (1978) Nature 271: 761-763), the present study examined the postnatal development of these innervation patterns, especially just before and just after the reported "critical period" for visual plasticity. A dense serotonergic innervation of layer IV is present at birth along with sparse innervation of other laminae. The adult pattern of serotonergic innervation, which is similar to that in the squirrel monkey but even more specifically laminated, becomes evident by 6 weeks of age. In the adult pattern, the most dense innervation remains in layers IVb and IVc. A much lower density of noradrenergic than of serotonergic fibers is evident at all ages examined. As with serotonin, the lowest density of fibers is observed at birth. By about 2 months of age these noradrenergic fibers have become more dense, and their laminar distribution is similar to that of adult cynomolgus which is similar to adult squirrel monkey. These studies indicate that: (1) both types of innervation display a continuum of development, with no abrupt changes, (2) serotonergic innervation is more dense than noradrenergic innervation at every age examined, (3) these two transmitter systems exhibit very different laminar innervation patterns as early as birth, and (4) the greater laminar specialization of area 17 in cynomolgus versus squirrel monkeys is accompanied by corresponding enhanced laminar specialization of these monoaminergic afferents.

Aging↗
PubMed1994

Enzymatic activity and morphological differentiation in de novo innervated human muscle cultures.

In the present series of experiments, we studied the effects of developmental neural control on morphological differentiation and on the activity of muscle-specific (creatine kinase, CK; phosphoglycerate mutase, PGAM; phosphorylase, PPL; and phosphofructokinase, PFK) and non-specific (acid maltase, AM; glucose-6-phosphate dehydrogenase, G6PD), human muscle enzymes in de novo innervated muscle cultures. Following innervation of muscle cultures, we noted an increase in the activity of CK, PPL, PFK and AM along with a reduction in G6PD activity. There was also a change of the CK isoenzymes present in the myotubes, i.e. BB and MB are the major isoenzymes in non innervated cultures, but MM becomes predominant following innervation. In the case of PGAM, the only isoenzyme present in the non innervated cultures was BB while the MM isoform appeared only after a prolonged innervation period in most cases--with the exception of AM--these changes in enzyme activity and in the type of isoenzymes present, demonstrate that innervated cultures are more similar to mature muscle. This maturation of enzymatic activity correlates well with the morphological maturation of the myotubes observed following innervation. Such innervated cultures therefore represent a better model with which to study the morphological and biochemical abnormalities associated with neuromuscular diseases.

Creatine Kinase↗
PubMed1989

Innervation of the renal proximal convoluted tubule of the rat.

Experimental data suggest the proximal tubule as a major site of neurogenic influence on tubular function. The functional and anatomical axial heterogeneity of the proximal tubule prompted this study of the distribution of innervation sites along the early, mid, and late proximal convoluted tubule (PCT) of the rat. Serial section autoradiograms, with tritiated norepinephrine serving as a marker for monoaminergic nerves, were used in this study. Freehand clay models and graphic reconstructions of proximal tubules permitted a rough estimation of the location of the innervation sites along the PCT. In the subcapsular nephrons, the early PCT (first third) was devoid of innervation sites with most of the innervation occurring in the mid (middle third) and in the late (last third) PCT. Innervation sites were found in the early PCT in nephrons located deeper in the cortex. In juxtamedullary nephrons, innervation sites could be observed on the PCT as it left the glomerulus. This gradient of PCT innervation can be explained by the different tubulovascular relationships of nephrons at different levels of the cortex. The absence of innervation sites in the early PCT of subcapsular nephrons suggests that any influence of the renal nerves on the early PCT might be due to an effect of neurotransmitter released from renal nerves reaching the early PCT via the interstitium and/or capillaries.

Animals↗