摘要:

AbstractIt is known that acetylcholinesterase is secreted by the dopaminergic neurons of the substantia nigra and has a subsequent action independent of cholinergic transmission. Although non‐cholinergic actions of this protein have been demonstrated, the subsequent fate of acetylcholinesterase is unknown. One possibility is that acetylcholinesterase is taken up following secretion into the extracellular space. This hypothesis has been testedin vivo, in both conscious and anaesthetized guinea‐pigs. Exogenous acetylcholinesterase (2–20 pM) was infused via a push‐pull cannula implanted into either the substantia nigra or the surrounding extranigral regions; the amount subsequently recovered in the perfusate was then compared with control values. Only when the push‐pull cannulae were implanted in the substantia nigra was there a marked decrease in the amount of acetylcholinesterase recovered; this selective retention was abolished when the perfusion medium was cooled to 4°C or when the experiment was performed post mortem. Direct visualization of immunocytochemically identified nigral dopaminergic cells revealed co‐localized deposits of labelled, exogenous acetylcholinesterase. Moreover, when exogenous acetylcholinesterase was boiled to prevent detection by the assay system and to eliminate any classical enzymatic action, an enhancement in perfusate levels of endogenous acetylcholinesterase was observed from nigral but not from extranigral sites, indicating that endogenous and exogenous acetylcholinesterases were in competition. These results suggest that, within the substantia nigra, secreted acetylcholinesterase may be subject to a temperature‐ and energy‐dependent

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00330.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe rat prefrontal cortex is densely innervated by dopaminergic fibres originating in the mesencephalic ventral tegmental area, and dopamine applicationin vivohas an inhibitory effect. We have studied the effects of dopamine on the persistent sodium current that is present in prefrontal cortex neurons and on the subthreshold electrophysiological responses generated by that current: a slow depolarization and a fast oscillatory activity. Experiments were made in coronal slices of rat frontal cortex (300–400 pm thickness) and intracellular recordings from regularly spiking cells were obtained with 3 M potassium acetate‐filled glass microelectrodes (80–150 MΩ). Dopamine was applied dissolved in the extracellular medium and, in current‐clamp recordings, reversibly inhibited the slow subthreshold depolarization. Dopamine was ineffective when applied after tetrodotoxin (1 μM) had blocked the action potentials. This inhibition was dose‐dependent in the range of 0.1–10 μM. Dopamine, applied at 10 μM, decreased the steady‐state firing frequency and also inhibited the subthreshold fast oscillatory activity. The currents activated in the subthreshold range were recorded with the single‐electrode voltage‐clamp technique and a clear persistent, tetrodotoxin‐sensitive component was isolated. This component was inhibited by 50% in a reversible way by 20 μM dopamine. These results show that dopamine increases the threshold for spike firing and suggest a mechanism for the inhibitory action of this neurotransmitter

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00331.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractUsing monoiodinated peptide YY (PYY) and galanin as radioligands, and neuropeptide Y (NPY) fragments, the distribution of NPY binding sites and its subtypes Y1 and Y2, and of galanin binding sites, was investigated in rat and monkey lumbar (L) 4 and L5 dorsal root ganglia (DRG) and spinal cord before and after a unilateral sciatic nerve cut, ligation or crush. Receptor autoradiography revealed that [125I]PYY bound to some DRG neurons and a few nerve fibres in normal rat DRG, and most of these neurons were small. NPY binding sites were observed in laminae I–IV and X of the rat dorsal horn and in the lateral spinal nucleus, with the highest density in laminae 1–11. [125I]NPY binding was most strongly attenuated by NPY13–36, a Y2 agonist, and partially inhibited by [Leu31,Pro34]NPY, a Y1 agonist, in both rat DRG and the dorsal horn of the spinal cord. These findings suggest that Y2 receptors are the main NPY receptors in rat DRG and dorsal horn, but also that Y1 receptors exist. After sciatic nerve cut, PYY binding markedly increased in nerve fibres and neurons in DRG, especially in large neuron profiles, and in laminae III‐IV of the dorsal horn, as well as in nerve fibres in dorsal roots and the sciatic nerve. Incubation with NPY13–36completely abolished PYY binding, which was also reduced by [Leu,31Pro34] NPY. However, the increase in PYY binding seen in laminae I–IV of the ipsilateral dorsal horn after axotomy was not observed after coincubation with [Leu31, Pro34] NPY. NPY binding sites were seen in a few neurons in monkey DRG and in laminae I‐II, X and IX of the monkey spinal cord. The intensity of PYY binding in laminae I‐II of the dorsal horn was decreased after axotomy. Galanin receptor binding sites were not observed in rat DRG, but were observed in the superficial dorsal horn of the spinal cord, mainly in laminae I‐II. Axotomy had no effect on galanin binding in rat DRG and dorsal horn. However, galanin receptor binding was observed in many neurons in monkey L4 and L5 DRG and in laminae I–IV and X of monkey L4 and L5 spinal cord, with the highest intensity in laminae I‐II. No marked effect of axotomy was observed on the distribution and intensity of galanin binding in monkey DRG or spinal cord. The present results indicate that after axotomy the synthesis of NPY receptors is increased in rat DRG neurons, especially in large neurons, and is transported to the laminae I–IV of the ipsilateral dorsal horn and into the sciatic nerve. No such up‐regulation of the NPY receptor occurred in monkey DRG after axotomy. The Y2 receptor seems to be the main NPY receptor in DRG and the dorsal horn of the rat and monkey spinal cord, but Y1 receptors also exist. The increase in NPY binding sites in laminae I–IV of the dorsal horn after axotomy partly represents Y1 receptors. In contrast to the rat, galanin binding sites could be identified in monkey lumbar DRG. No effect of axotomy on the distribution of galanin binding sites in rat or monkey DRG and dorsal horn was detected, suggesting their presence on local dorsal horn neu

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00332.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractPrevious studies in our laboratory using a transplantation model have shown that target tissues of some autonomic neurons, including cerebral blood vessels, exert a controlling influence on nerve fibre loss in old age. The present study was undertaken in order to discover whether the influence of targets extends to controlling age changes in specific populations of nerves. In old rats, we have demonstrated a significant decrease of ‐50% in the sympathetic innervation of middle cerebral arteries, using tyrosine hydroxylase‐like immunoreactivity. Following transplantation, tyrosine hydroxylase‐like immunoreactive nerve density on both young and old implanted middle cerebral arteries mirrored the nerve densities seen in normal, non‐transplanted vessels. Furthermore, implanted tissue from old donors became reinnervated with a nerve density ‐50% less than that of young implanted vessels. Treatment of transplants with nerve growth factor, however, was able to reverse these age changes and restore the sympathetic innervation of aged middle cerebral arteries to levels above those seen in young middle cerebral arteries. These results suggest that the pattern and density of sympathetic innervation that the middle cerebral artery receives is determined by the target rather than by the neurons supplying the tissue. The ability of nerve growth factor to induce regrowth in sympathetic neurons innervating ageing target tissues implies that age‐related neuronal atrophy may be due to reduced synthesis or availability of target‐derived neurotr

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00333.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractLight‐induced phase shifts of circadian rhythmic locomotor activity are associated with the expression of c‐Jun, JunB, c‐Fos and FosB transcription factors in the rat suprachiasmatic nucleus, as shown in the present study. In order to explore the importance of c‐Fos and JunB, the predominantly expressed AP‐1 proteins for the phase‐shifting effects of light, we blocked the expression of c‐Fos and JunB in the suprachiasmatic nucleus of male rats, housed under constant darkness, by intracerebroventricular application of 2 μ1 of 1 mM antisense phosphorothioate oligodeoxynucleotides (ASO) specifically directed againstc‐fosandJunBmRNA. A light pulse (300 lux for 1 h) at circadian time 15 induced a significant phase shift (by 125 ± 15 min) of the circadian locomotor activity rhythm, whereas application of AS0 6 h before the light pulse completely prevented this phase shift. Application of control nonsense oligodeoxynucleotides had no effect. ASO strongly reduced the light‐induced expression of c‐Fos and JunB proteins. In contrast, light pulses with or without the control nonsense oligodeoxynucleotides evoked strong nuclear c‐Fos and JunB immunoreactivity in the rat suprachiasmatic nucleus. These results demonstrate for the first time that inducible transcription factors such as c‐Fos and JunB are an essential part of fundamental biological processes in the adult mammalian nervous system, e.g. of light‐induced phase shifts

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00334.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe calcitonin/CGRP gene is transcribed in thyroid C cells and some neuronal cells but not in other cell types. Although the promoter sequences mediating gene activity in thyroid C cells have been extensively studied, the elements responsible for promoter activity in neuronal cells and its stimulation by nerve growth factor (NGF) have not previously been defined. We report the first use of the calcium phosphate procedure to successfully transfect adult rat dorsal root ganglion neurons, which naturally express the calcitonin/calcitonin gene‐related peptide (CGRP) in an NGF‐inducible manner. This method was used to characterize the elements in the calcitonin/CGRP promoter which are responsible for its basal activity and NGF inducibility in DRG neurons and in PC12 cells, a neuronally derived cell line which does not naturally express the calcitonin/CGRP gene. Although the sequences required for basal activity are similar in each cell type, we show that a minimal calcitonin/CGRP promoter is NGF‐responsive in dorsal root ganglion cells, but that upstream sequences are required for such inducibility in PC12

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00335.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractFollowing transection of the postcommissural fornix in the adult rat, fibres retract from the lesion zone but then start to regrow within their former pathway up to the lesion site, where they terminate. The fibres neither penetrate nor bypass this region. In order to define the molecular mechanisms that cause regenerative failure at the lesion site, we analysed the spatiotemporal relationship between clearance/re‐expression of myelin constituents and axon sprouting. Using immunocytochemical methods, we investigated the distribution of myelin‐associated growth inhibitor (Nl‐35/250) and myelin basic protein after transection of the postcommissural fornix. In the studies described here we demonstrate the sequential removal of neurofilaments and myelin constituents in a perilesion zone and at the lesion site. The removal of myelin constituents was followed by the extensive regrowth of fornix fibres in the proximal segment. However, these fibres stopped at the lesion site, an area that lacked immunostaining for Nl‐35/250 and. In the distal stump we observed the disappearance of neurofilament along the entire fornix segment but spatial differences in the removal of myelin constituents. While both NI‐35/250 and myelin basic protein disappeared in the perilesion zone, they persisted in the more distal segment for at least 28 months after lesion. In conclusion, our study indicates that the onset of axon sprouting is correlated with the removal of myelin basic protein and NI‐35/250. Furthermore, we suggest that it seems unlikely that the myelin growth inhibitor NI‐35/250 constitutes the stop signal of the axon growth barrier in the tran

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00336.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractDifferent regions of the body of an animal have their own shape and location within visual space. Accordingly, in the superior colliculus there are somatosensory‐visual bimodal neurons receiving tactile and visual input from the same region of space. In newborn mice, we changed the position of some body parts within visual space in order to see what happened to the alignment of the somatosensory and visual receptive fields of superior colliculus bimodal neurons. To do this, we modified the shape of the head by displacing the superior vibrissae and the ears, normally in the superior portion of visual space, into the inferior visual space. Analogously, we bent the inferior vibrissae into the superior visual space. At the sixth postnatal week we recorded from somatosensory‐visual bimodal neurons of the deep layers of the superior colliculus and found that the tactile and visual receptive fields were aligned. Neurons receiving tactile input from the downward‐displaced superior vibrissae and ears showed visual receptive fields in the inferior portion of visual space, whereas neurons receiving input from the upward‐displaced inferior vibrissae showed visual receptive fields in the superior visual space. These results show that an experience‐dependent interaction between visual and somatosensory inputs occurs during development, and that early exposure to abnormal visual‐somatosensory experience modifies the organization of multisensory neurons in the superior

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00337.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractAs an estimate of the numerical importance of GABA‐containing neurons during development, their quantitative distribution was analysed in the primary somatosensory cortex of rats between postnatal days (P) 5 and 60, using the disector method and GABA postembedding immunocytochemistry. In relation to the overall number of neurons in the barrel field cortex, the proportion of GABA neurons showed an early significant decrease between P5 and P10 from 14 to 11%, most likely due to termination of transient expression of GABA by some cells. It then remained stable until P20, after which it started slowly but steadily to increase, reaching 14% of the total at P60. The absolute number of GABA neurons also increased by nearly 50% during that period, whereas the number of all neurons remained constant. These changes are seemingly due to a subpopulation of neurons, shown to be of small size, which express GABA late in development. Thus, anatomical adjustments of the cortical GABA system may be observed at least until the end of the second postnatal month, reflecting both delayed maturation and adaptation of this inhibitory circuitry. We suggest the existence of three subpopulations of cortical GABA neurons depending on the time of onset and the regulation of their GABA expression: (i) neurons which express GABA before completion of migration and thus provide for its neurotrophic influence. (ii) neurons which express GABA immediately after completion of migration and build up the cortical inhibitory circuitry, and (iii) neurons which express GABA later in development and represent a substrate of experience dependent plasticit

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00338.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe afferent properties of nerve fibres innervating the hairy skin of the pig hind limb were investigated by recording from 142 single units from the saphenous nerve. Identified single units were isolated using maximal electrical stimulation of the nerve trunk. Afferent units were classified on the basis of their responses to a range of stimuli, both thermal (heating to 60°C and cooling to 10°C) and mechanical (air jet, von Frey type filaments with forces of 0.1–250 mN, and strong pressure with a blunt needle). A‐fibre units (conduction velocity 6.3–64 m/s,n= 60) fell into categories that have been described in hairy skin in other mammalian species. Most were mechanoreceptors, although seven typical A‐fibre mechanical nociceptors with large, multipoint fields were also isolated. No cutaneous receptive field could be found for 15% of A‐fibre units. Out of 62 C‐fibre units (conduction velocity 0.49–2 m/s) 40% had no cutaneous field for pressure, heat or cold. Of the C‐fibre units with cutaneous fields, 42% were polymodal nociceptors, 38% were mechanoreceptors with a variety of properties, including some excited by noxious heat, and 19% were heat‐only nociceptors. C‐polymodal nociceptors had large receptive fields up to 12.5 mm across and did not sensitize following strong heating. Twenty units conducted at 2–6.3 m/s, between the main C‐ and A‐fibre bands, and were varied in their responses. Some had properties identical to C‐fibre mechanoreceptors whilst four were sensitive cold thermoreceptors and one was a polymodal nociceptor. Two units were mechanical nociceptors with small receptive fields. The innervation of pig skin thus has some features like that of primates, such as the presence of C‐heat nociceptors and the large receptive fields of C‐polymodal nociceptors. However, other features were like non‐primates (e.g. the minimal heat‐sensitivity of A‐mechanical nociceptors) or were unique (the heat‐sensitive mechanoreceptors and the lack of heat sensitization in

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1995.tb00339.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY