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1.
目的:本研究对内嗅皮质- 海马通路的各个亚支的发生进行了调查。方法:对不同龄大鼠脑用DiI、DiO、快兰示踪法及calretinin 免疫细胞化学法处理。结果:槽通路、海马交通通路于胚胎16 天(E16)开始发生,而穿通通路分别始见于胚胎17天海马的腔隙分子层和生后第2天齿状回外分子层。DiI的逆行标记显示内嗅皮质-海马通路主要来自内嗅皮质中II到IV层神经元。另外,calretinin免疫细胞化学法显示Cajal-Retzius (CR)细胞早在胚胎16天存在于海马的腔隙分子层,DiI和calretinin免疫细胞化学法双重标记显示CR细胞和内嗅皮质转入纤维之间可能存在密切的接触关系。结论:嗅皮质-海马通路的各个亚支是按照上述各自的时间表进行发生,CR细胞和穿通纤维的发育时空关系提示该细胞对内嗅皮质传入纤维寻径具有引导作用。  相似文献   

2.
Deng JB  Yu DM  Li MS 《神经科学通报》2006,22(6):305-314
本研究对内嗅皮质一海马通路的各个亚支的发生进行了调查。方法:对不同龄大鼠脑用DiI、DiO、快兰示踪法及calretinin免疫细胞化学法处理。结果:槽通路、海马交通通路于胚胎16天(E16)开始发生,而穿通通路分别始见于胚胎17天海马的腔隙分子层和生后第2天齿状回外分子层。DiI的逆行标记显示内嗅皮质.海马通路主要来自内嗅皮质中Ⅱ到Ⅳ层神经元。另外,calretinin免疫细胞化学法显示Cajal—Retzius(CR)细胞早在胚胎16天存在于海马的腔隙分子层,DiI和calretinin免疫细胞化学法双重标记显示CR细胞和内嗅皮质转入纤维之间可能存在密切的接触关系。结论:嗅皮质-海马通路的各个亚支是按照上述各自的时间表进行发生,CR细胞和穿通纤维的发育时空关系提示该细胞对内嗅皮质传入纤维寻径具有引导作用。  相似文献   

3.
4.
Chronic haloperidol treatment markedly increases dynorphin-related peptide contents in caudate-putamen, globus pallidus and substantia nigra. Leu-enkephalin levels follow dynorphin-related peptide concentrations in these areas while Met-enkephalin-related peptide contents are unchanged in the substantia nigra following a similar treatment. An acute haloperidol injection had no effect on any opioid peptide levels in the basal ganglia. This suggests that Leu-enkephalin is likely to be derived from prodynorphin in the rat striatonigral pathway. Moreover, the Leu-enkephalin/dynorphin projection appears to be under striatal dopaminergic control.  相似文献   

5.
The entorhino-hippocampal pathway is the major excitatory input from neurons of the entorhinal cortex on both ipsilateral and contralateral hippocampus/dentate gyrus. This fiber tract consists of the alvear path, the perforant path and a crossed commissural projection. In this study, the histogenesis and development of the various subsets of the entorhino-hippocampal projection have been investigated. DiI, DiO, Fast Blue tracing and calretinin immunocytochemistry as well as were carried out with pre and postnatal rats at different developmental stages. The alvear path and the commissural pathway start to develop as early as embryonic day E16, while the first perforant afferents reach the stratum lacunosum-moleculare of the hippocampus at E17 and at outer molecular layer of the denate gyrus at postnatal day 2. Retrograde tracing with DiI identifies entorhinal neurons in layer II-IV as the developmental origin of the entorhino-hippocampal pathway. Furthermore, calretinin immunocytochemistry revealed transitory Cajal-Retzius cells in the stratum lacunosum-moleculare of the hippocampus from E16. DiI labeling of entorhinal cortex fibers and combined calretinin-immunocytochemistry reveal a close relationship between Cajal-Retzius cells and entorhinal afferents. This temporal and spatial relationship suggests that Cajal-Retzius cell serves as a guiding cue for entorhinal afferents at early cortical development.  相似文献   

6.
背景:辛伐他汀可促进体外培养的人或鼠骨髓基质干细胞向成骨细胞分化,但作用机制尚不清楚。 目的:观察辛伐他汀对大鼠骨髓基质干细胞向成骨细胞分化过程中Wnt与骨形态发生蛋白2信号途径中相关因子表达的影响。 方法:取6周龄雌性SD大鼠双侧股骨、胫骨全骨髓进行体外成骨细胞诱导培养。实验分为对照组及SIM组。SIM组加入浓度为10-7 mol/L辛伐他汀,对照组加入等量无水乙醇和PBS。培养14 d,行碱性磷酸酶染色,28 d时,行von Kossa染色观察细胞外基质矿化情况;培养14,21 d,免疫荧光细胞化学染色观察成骨细胞中β-catenin,Smad1/5,Cbfa1的表达及分布。 结果与结论:大鼠骨髓基质干细胞经体外诱导后可分化为具有碱性磷酸酶活性和矿化细胞外基质能力的成熟成骨细胞。辛伐他汀可显著上调骨髓基质干细胞成骨分化过程中碱性磷酸酶的表达。同时,与对照组比较,SIM组β-catenin,Smad1/5,Cbfa1表达明显增多(P < 0.05),且呈现明显的核内聚集趋势。说明辛伐他汀促进骨髓基质干细胞向成骨细胞分化的作用可能与调控Wnt与骨形态发生蛋白2信号通路中相关因子的表达及细胞内分布有关。  相似文献   

7.
There are two prevailing notions regarding the involvement of the corticobasal ganglia system in value‐based learning: (i) the direct and indirect pathways of the basal ganglia are crucial for appetitive and aversive learning, respectively, and (ii) the activity of midbrain dopamine neurons represents reward‐prediction error. Although (ii) constitutes a critical assumption of (i), it remains elusive how (ii) holds given (i), with the basal‐ganglia influence on the dopamine neurons. Here we present a computational neural‐circuit model that potentially resolves this issue. Based on the latest analyses of the heterogeneous corticostriatal neurons and connections, our model posits that the direct and indirect pathways, respectively, represent the values of upcoming and previous actions, and up‐regulate and down‐regulate the dopamine neurons via the basal‐ganglia output nuclei. This explains how the difference between the upcoming and previous values, which constitutes the core of reward‐prediction error, is calculated. Simultaneously, it predicts that blockade of the direct/indirect pathway causes a negative/positive shift of reward‐prediction error and thereby impairs learning from positive/negative error, i.e. appetitive/aversive learning. Through simulation of reward‐reversal learning and punishment‐avoidance learning, we show that our model could indeed account for the experimentally observed features that are suggested to support notion (i) and could also provide predictions on neural activity. We also present a behavioral prediction of our model, through simulation of inter‐temporal choice, on how the balance between the two pathways relates to the subject's time preference. These results indicate that our model, incorporating the heterogeneity of the cortical influence on the basal ganglia, is expected to provide a closed‐circuit mechanistic understanding of appetitive/aversive learning.  相似文献   

8.
Fiber connections of the rostrolateral region of the lateral preglomerular nucleus (PGlr) were studied by tract-tracing methods in carp and goldfish. The PGlr receives fibers from the optic tectum, ventrolateral nucleus of semicircular torus, ventromedial thalamic nucleus, medial pretoral nucleus, anterior tuberal nucleus, subglomerular nucleus, and (unexpectedly) also from the retina. Dendritic morphology of tecto-preglomerular neurons suggests that they receive retinal inputs. The PGlr can be further subdivided into dorsal (PGlr-d) and ventral (PGlr-v) zones, both of which are composed of somata and neuropil layers. Retinal and tectal fibers terminate mostly in the neuropil layer of the PGlr-d with the retinal terminals concentrated medially and tectal terminals laterally. Lateral line toral fibers terminate mainly in a lateral portion and ventromedial thalamic fibers in a medial portion of the somata layer of the PGlr-d. Auditory fibers from the medial pretoral nucleus and anterior tuberal nucleus terminate in the PGlr-v. The central nucleus of the semicircular torus also projects sparse fibers to the PGlr-v. The PGlr projects to the lateral, central, and medial parts of the dorsal telencephalic area, and the latter telencephalic part sends descending fibers to the PGlr. Differential distribution patterns of PGlr-d and PGlr-v fibers are noted within the dorsal telencephalic parts, suggesting that different sensory modalities may be represented in distinct regions at least to a certain degree.  相似文献   

9.
Neurotensin (NT), a brain-gut peptide, possesses many biological actions similar to those reported for neuroleptics. Moreover, it has been shown that NT alters dopaminergic activity of both nigrostriatal and mesolimbic pathways. We now report that NT receptors are located on dopaminergic cell bodies in both systems. However, the proportion of NT receptors on presynaptic dopaminergic terminals appears to be different. NT receptor sites are mainly found on presynaptic dopaminergic terminals in the caudate-putamen while they are pre- and post-synaptically located in the nucleus accumbens and the olfactory tubercule. NT receptors differential localization in these two pathways could be used as a model to study the comparative physiology of various dopaminergic brain systems.  相似文献   

10.
Calcineurin is the calcium (divalent cations)-dependent calmodulin-stimulated phosphoprotein phosphatase which is capable of dephosphorylating various substrate proteins. The subcellular and regional distribution of calcineurin in the rat brain has been studied by light and electron microscopic immunohistochemistry using antiserum against calcineurin. Immunoreactivity was observed in many neurons but was not detected in glial cells, such as astrocytes, oligodendrocytes and ependymal cells by the PAP method. Light microscopy demonstrates strong immunoreactivity in neuronal somata and neurites. By electron microscopy, calcineurin immunoreactivity was found to be present in dendrites including postsynaptic densities, somata, spines, axons and terminals. Calcineurin immunoreactivity was present in neurons throughout the brain, but a marked regional variation in strength of the immunoreactivity was observed. The caudatoputamen, hippocampal formation, and substantia nigra were strongly stained. Cerebral and cerebellar neocortex showed moderate immunoreactivity. In substantia nigra and globus pallidus, only neurites were stained, but neuronal somata not. The staining of the substantia nigra was thought to be due to that of the nerve terminals originating from the caudatoputamen, in view of the findings by cerebral hemitransection and electron microscopic immunohistochemistry. We developed an enzyme-immunoassay (EIA) for calcineurin. The sensitivity of the EIA was 1 ng (13 fmol) of calcineurin. We determined the level of calcineurin in various regions of the rat brain. The caudate nucleus, putamen and hippocampal formation showed a high concentration of calcineurin. The results are consistent with those obtained by immunohistochemistry.  相似文献   

11.
In this issue of BBI Melbourne et al describe a reduced activity of the JAK-STAT1 pathway in leukocytes of early and acute schizophrenia patients. This editorial discusses the report of Melbourne et al as being in accord with the view that active forms of schizophrenia are characterized by a de-activation of the Th1 driven M1/JAK-STAT1 mediated pro-inflammatory pathway in myeloid cells (macrophages, dendritic cells and microglia). Myeloid cells can be inflammatory activated and de-activated via various different molecular pathways (leading to various types of macrophages, such as e.g. various M1, various M2 and atherosclerosis related macrophages). There are data in the literature that pathways related to the Th17 driven MAP-kinase pro-inflammatory M1 pathway are activated in the myeloid cells of early and acute schizophrenia. The question thus arises what the intracellular molecular processes are which drive the complex inflammatory set points of macrophages and microglia in early and acute forms of schizophrenia.  相似文献   

12.

Objectives

The coagulation protease cascade plays the central requisite role in initiation of arterial atherothrombosis. However, the relative participation of the extrinsic as compared to the intrinsic pathway is incompletely resolved. We have investigated in vivo the relative importance of the extrinsic and intrinsic pathways to define which is more essential to atherothrombosis and therefore the preferable prophylactic therapeutic target. We further addressed which type of plaque associated macrophage population is associated with the thrombotic propensity of atherosclerotic plaques.

Methods

Both photochemical injury and ferric chloride vascular injury models demonstrated arterial thrombosis formation in ApoE deficient mice. We found that direct interference with the extrinsic pathway, but not the intrinsic pathway, markedly diminished the rate of thrombus formation and occlusion of atherosclerotic carotid arteries following experimental challenge. To explore which plaque macrophage subtype may participate in plaque thrombosis in regard to expression tissue factor pathway inhibitor (TFPI), bone marrow derived macrophages of both M and GM phenotypes expressed tissue factor (TF), but the level of TFPI was much greater in M- type macrophages, which exhibited diminished thrombogenic activity, compared to type GM-macrophages.

Results and conclusions

Our works support the hypothesis that the TF-initiated and direct extrinsic pathway provides the more significant contribution to arterial plaque thrombogenesis. Activation of the TF driven extrinsic pathway can be influenced by differing colony-stimulating factor influenced macrophage TFPI-1 expression. These results advance our understanding of atherothrombosis and identify potential therapeutic targets associated with the extrinsic pathway and with macrophages populating arterial atherosclerotic plaques.  相似文献   

13.
We examined the distribution of neurons containing immunoreactivity for three calcium-binding proteins, calbindin, parvalbumin and calretinin, as well as nonphosphorylated neurofilament protein, in cortical areas along the ventral and dorsal cortical visual pathways, and in ventrally-directed somatosensory and auditory cortical pathways. Calbindin-immunoreactive pyramidal neurons showed the most prominent regional differences. They were largely restricted to layers II and III and their number monotonically increased from the primary sensory areas to the anteroventral areas along the ventral visual pathway and along the ventrally-directed somatosensory and auditory pathways. The number of calbindin-immunoreactive pyramidal neurons in layers II and III also increased along the dorsal visual pathway, but the number in the last recognized stage of the dorsal visual pathway (area 7a) was significantly smaller than that at the corresponding stage in the ventral visual pathway (TE). The number of calbindin-immunoreactive pyramidal neurons was highest in layers II and III of areas 35/36, TG, and TF/TH, which represent terminal cortical regions of the pathways. These results show neurochemical differences between cortical areas located at early and late stages along serial corticocortical pathways, as well as confirming differences between pyramidal neurons in the supragranular and infragranular layers.  相似文献   

14.
18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, is a potential treatment for drug addiction. 18-MC has been shown to decrease self-administration of drugs (e.g., morphine, methamphetamine, nicotine) and attenuate opioid withdrawal in rats. In previous studies, systemic pretreatment with 18-MC abolished the sensitized increase in accumbens dopamine levels induced by chronic morphine administration. In vitro studies have shown that 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors, and alpha3beta4 antagonism is believed to be the primary mechanism responsible for 18-MC's effects on drug self-administration and possibly on morphine-induced changes in mesolimbic dopamine. While there are very low densities of alpha3beta4 nicotinic receptors in the mesolimbic pathway, these receptors are prominently localized in the medial habenula (MHb) and in the interpeduncular nucleus (IPN). These nuclei and the habenulo-interpeduncular pathway connecting them are believed to function as part of an alternate reward pathway modulating the dopaminergic mesolimbic pathway known to be involved in drug addiction. In the present study, to determine if 18-MC acts in the MHb or in the IPN, the effects of local infusion of 18-MC into these brain areas were assessed on mesolimbic dopamine responses to acute and repeated morphine treatment. Administration of 18-MC (10 mug) into either the IPN or MHb blocked the sensitized dopamine response to repeated morphine in the nucleus accumbens; 18-MC had no effect on the dopamine response to acute morphine. The results suggest that 18-MC acts in the habenulo-interpeduncular pathway to modulate the effects of repeated morphine in the dopaminergic mesolimbic system.  相似文献   

15.
The present experiments investigate the effects of neonatal lesions upon projection patterns of the uncrossed retinotectal pathway in albino rats. The results indicate that enlargement of the terminal field from one eye can be induced either by a contralateral optic tract lesion or by removal of the opposite eye at birth. The extent of the enlargement is more prominent in the latter case. If an optic tract lesion is accompanied by eye enucleation on the side ipsilateral to the tract lesion, the uncrossed retinotectal projection from the remaining eye will undergo further enlargement. However, optic fiber counts show that such an enlargement of the terminal field is not due to a significant increase in the number of uncrossed optic axons which contribute to the enlarged projection, but rather to an increased terminal arbor of individual axons (as shown by results from fiber counts). While a severe ganglion cell loss was observed in the retina contralateral to a tract lesion, a substantial population of cells persists in the ganglion cell layer and the number of cells appears much higher than the number of uncrossed optic axons arising from the same eye. The implications of these findings are discussed in relation to results reported in previous studies.  相似文献   

16.
Early gene induction by L-DOPA in the striatum of dopamine denervated rats represents a useful way to study long-term modifications produced by this drug. The effects of acute and subchronic L-DOPA administration on zif-268 mRNA expression were compared in 6-hydroxydopamine-lesioned rats. Rats received a subchronic intermittent L-DOPA (6 mg/kg) treatment, which produces behavioural sensitization, a correlate of dyskinetic movements. Three days after interruption of subchronic treatment, zif-268 mRNA was evaluated after an L-DOPA challenge. Zif-268 mRNA levels increased in the lesioned dorsolateral striatum after either acute or subchronic L-DOPA administration. Double labelling of striatal cells with zif-268 and enkephalin or dynorphin mRNA probes was performed to assess neuronal activation in the indirect and direct output pathway. Single acute L-DOPA significantly increased zif-268 in all striatal neurons reflecting a hyperresponsiveness of dopamine-depleted striatum. After subchronic L-DOPA, zif-268 mRNA labelling was still increased in the striatonigral pathway, limited to dynorphin(+) neurons, whereas in all other neurons it was similar to the control value. Results suggest that striatal neurons responding to acute L-DOPA differ from those responding to subchronic L-DOPA. L-DOPA-induced behavioural sensitization was associated to a down-regulation in the responsiveness of striatopallidal and striatonigral dynorphin(-) neurons, whereas in striatonigral neurons containing dynorphin a hyperresponsiveness to L-DOPA was observed. High levels of zif-268, together with a persistent hyperresponsiveness of striatonigral dymorphinergic neurons and hyporesponsiveness of striatopallidal neurons, by creating an unbalanced state of striatal efferent neurons, may be implicated in dyskinetic movements observed in Parkinson's disease (PD).  相似文献   

17.
Using neural pathway tracing and immunohistochemical technique, the striato-direct pathway (BDA3 kDa injected into the rat lateral globus pallidus) and striato-indirect pathway (BDA3 kDa injected into the substantia nigra pars reticulata) neurons were specifically labeled, and then subjected to double-labeled immunohistochemistry for mu-OPIOID Receptor (specifically-labeled striatal patch compartment), D1, and D2, respectively. The experimental findings showed that there are no statistically significant differences in the soma diameter and the number of primary dendrites between the striato-direct (substantia nigra pars reticularis) and indirect (globus pallidum externum) neurons labeled retrograde by BDA3 kDa. In addition, these two kinds of projection neurons revealed no obvious coexistence. This evidence indicates that as a highly sensitive neural pathway tracer, BDA could yield reliably and exquisitely detailed labeling of target neurons and synaptic structures. The variance of the morphologic structures and the localization of neurons were not statistically significant between the striato-substantia nigra pars reticularis and the globus pallidum externum projection neurons. Mesencephalic and thalamic neurons correlated with striatal neurons in morphology. Especially the latter which make typical excitatory synaptic contacts with striato-direct and -indirect neurons. Thus, this evidence suggests that thalamic neurons may extensively excite striatal neurons.  相似文献   

18.
The present study examined whether ganglioside treatments would affect an enzyme marker (glucose-6-phosphate dehydrogenase; G6PDH) of neural metabolism in an established model system (the hippocamposeptal projection) of deafferentation and sprouting. Rats were subjected to unilateral transections of the fimbria-fornix (FF) in order to (1) interrupt the hippocamposeptal projection, (2) deafferent the lateral septal nucleus (LSN) ipsilaterally, and (3) induce sprouting by the contralateral FF. In untreated rats which were killed at 2-4 days postlesion, histochemical staining for G6PDH was reduced by 35-40% in the deafferented LSN relative to the contralateral side. However, at 6-8 days (i.e., when sprouting begins), staining intensity returned toward contralateral values (i.e., recovered). This pattern of changes in G6PDH staining was not observed in the caudate nucleus adjacent to the LSN. In ganglioside-treated rats which were killed at 4 days, there was a significantly smaller reduction of G6PDH staining in the deafferented LSN (23%; P = .05). This effect was not observed in the LSN of treated rats killed at 2 days, nor in the caudate nucleus at either time point. The present data indicate that (1) FF transection results in a reduction and subsequent recovery of G6PDH staining in the deafferented LSN; and (2) ganglioside treatments may accelerate the onset of the recovery of G6PDH activity. We suggest that gangliosides' effect on G6PDH reflects an acute enhancement of biosynthetic events in deafferented neurons.  相似文献   

19.
The trajectories and telencephalic terminal fields of neurons within the area ventralis of Tsai (AVT) and nucleus tegmenti pedunculopontinus pars compacta (TPc) were determined in the pigeon by using amino acid autoradiography and horseradish peroxidase histochemistry. Previous histochemical studies have considered these cell groups comparable to the A10 and A9 components of the mammalian nigral complex. The results show the efferents derived from these cell groups ascend to the telencephalon via the medial and lateral forebrain bundles, ansa lenticularis, and quintofrontal and occipitomesencephalic tracts. All projections are bilateral and symmetrical, although projections to the contralateral hemisphere are extremely sparse. Within the telencephalon many cell fields receive projections from the AVT and TPc nuclei; however, the most substantial projections reach structures within the basal telencephalon, especially the paleostriatal complex. Within the paleostriatal complex the paleostriatum augmentatum (PA) receives a very heavy projection from the TPc. AVT projections reach primarily rostromedial portions of PA as well as the lobus parolfactorius. The large-celled portions of the paleostriatum including the paleostriatum primitivum and nucleus intrapeduncularis do not appear to receive projections from either AVT or TPc neurons. Projections from AVT and TPc neurons terminate within other structures of the basal telencephalon including the lateral and medial septal nuclei, the olfactory tubercle, the ventral paleostriatum and the preoptic area. Pallial derivatives including the hyperstriatum dorsale, hyperstriatum ventrale, dorsal archistriatum, and hippocampus also receive projections from AVT and TPc neurons, although these projections are much sparser than those reaching subpallial structures. Large portions of the telencephalon including the hyperstriatum accessorium, most of the hyperstriatum ventrale, much of the archistriatum, and much of the neostriatum do not receive projections from AVT or TPc neurons. Furthermore, there is substantial overlap between the telencephalic projections of TPc and AVT neurons, as well as considerable overlap between the projections of both these nigral cell groups and the projections of the locus coeruleus complex in the pigeon. This high degree of overlap between locus coeruleus and nigral telencephalic terminal fields is quite different from the condition in mammals and suggests possible functional divergence for some of these pathways in contemporary amniote forms.  相似文献   

20.
The optic tectum of vertebrates is an essential relay station for visuomotor behavior and is characterized by a set of connections that comprises topographically ordered input from the eyes and an output that reaches premotor hindbrain regions. In the avian tectofugal system, different ascending cell classes have recently been identified based on their dendritic and axonal projection patterns, although comparable information about the descending cells is missing. By means of retrograde tracing, the present study describes the detailed morphology of tectal output neurons that constitute the descending tectobulbar and tectopontine pathways in pigeons. Descending cells were more numerous in the dorsal tectum and differed in terms of 1) their relative amount of ipsi- vs. contralateral projections, 2) the location of the efferent cell bodies within different tectal layers, and 3) their differential access to visual input via dendritic ramifications within the outer retinorecipient laminae. Thus, the descending tectal system is constituted by different cell classes presumably processing diverse aspects of the visual environment in a visual field-dependent manner. We demonstrate, based on a careful morphological analysis and on double-labeling experiments, that the descending pathways are largely separated from the ascending projections even when they arise from the same layers. These data support the concept that the tectum is arranged as a mosaic of multiple cell types with diverse input functions at the same location of the tectal map. Such an arrangement would enable the tectal projections onto diverse areas to be both retinotopically organized and functionally specific.  相似文献   

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