Amygdala input to medial prefrontal cortex (mPFC) in the rat: A light and electron microscope study

This paper describes the termination pattern and synaptic connectivity of the pathway from the basolateral nucleus of the amygdala (BLA) to the medial prefrontal cortex (mPFC; areas 25, 32, and 24b) of the rat. Discrete injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) were made in the BLA and detailed light microscopical observations made of the distribution of PHA-L labelled fibres and boutons in the mPFC. Labelled fibres were distributed in two tiers: predominantly within deep layer 1/layer 2 and also in layers 5/6. Fibre plexi in layers 2 and 5 were highly varicose. Electron microscopical examination of 120 labelled boutons in area 32 (60 in layer 2 and 60 in layer 5) indicated that 116 (97%) established asymmetrical synaptic contacts with dendritic spines and 4 (3%) were in synaptic contact with small dendritic shafts. No significant differences in target structures were found between layers 2 and 5. The results indicate that BLA input to mPFC in the rat predominantly innervates spine bearing dendrites in layers 2 and 5. This suggests that the neuronal operations of these processes are influenced by direct feedforward excitation from the BLA.     

神经干细胞分化的神经元与尾状核神经元共培养的实验研究

目的研究大鼠神经干细胞(NSCs)分化后与尾状核神经元共培养时是否形成突触连接.方法分离培养大鼠NSCs及尾状核神经元,用绿色荧光蛋白重组腺相关病毒(eGFP)转染NSCs;将eGFP-NSCs 分化后和大鼠尾状核神经元共培养,利用免疫细胞化学方法和激光共聚焦显微镜分析结果.结果 eGFP-NSCs分化的神经元与尾状核神经元共培养时,两者有突触连接形成.结论 NSCs分化的神经元具有形成神经网络的能力.     

Changes in the structure of synaptic junctions during climbing fiber synaptogenesis

Synaptogenesis between climbing fiber axons and Purkinje cells involves both an orderly translocation of synaptic junctions over the Purkinje cell surface and an elimination of all but one innervating axon. We used thin-section and freeze-fracture electron microscopic techniques to study structural changes in synaptic junctions during this interval of synapse translocation and elimination. In freeze-fractured preparations, virtually all climbing fiber synaptic junctions with the perisomatic processes and somatic spines lacked the particle aggregates that characterized the extracellular half of the postsynaptic membrane of mature synaptic junctions with dendritic spines. Some climbing fiber junctions with the dendritic shaft in the second postnatal week were associated with such aggregates, despite the fact that these junctions are transient. Thus, during the interval when Purkinje cells initially were innervated by multiple climbing fibers, and subsequently denervated of all but one climbing fiber afferent per cell, only a few of the transient synaptic junctions on the cell body and proximal dendrites have associated particles. The presence of a particle aggregate at a synaptic junction does not appear to be correlated with the permanence of that junction and probably is not correlated with the capacity to support synaptic transmission. The particle aggregates might be indicative of relatively long-lived junctions, or might occur only at junctions formed by the climbing fiber that will persist in synaptic contact with the mature Purkinje cell.     

Surgical denervation increases protein tyrosine phosphatase activity in skeletal muscle

Protein tyrosine phosphorylation, which plays an important role in synapse formation at the neuromuscular junction, appears to be regulated by presynaptic neurons. Innervation increases whereas denervation decreases the phosphotyrosine content at the neuromuscular junction. The innervation-dependent tyrosine phosphorylation may result from elevated activity of protein tyrosine kinases; alternatively innervation may down-regulate the protein tyrosine phosphatase activity in the skeletal muscle. To investigate the possible neuronal control of protein tyrosine phosphatase activity at the neuromuscular junction, we have characterized protein tyrosine phosphatase activity in rat skeletal muscle and studied the effects of surgical denervation on the phosphatase activity. Protein tyrosine phosphatase activity in the skeletal muscle, assayed using src [³²P]-p hosphorylated myelin basic protein as a substrate, was both time- and protein concentration dependent and was inhibited by micromolar concentrations of vanadate and zinc ion, both of which are known to inhibit tyrosine phosphatases specifically. It was not affected, however, by chemicals known to inhibit acid and alkaline phosphatases or serine/threonine phosphatases. Surgical denervation caused an increase in protein tyrosine phosphatase activity in rat hindlimb muscles. The increase in phosphatase activity reached a maximum (2-fold above the normal) 4 days post-denervation and maintained a plateau for up to 24 days. The biochemical properties of the phosphatase activity in denervated muscle were similar to those of the phosphatase activity in the innervated muscles. These results demonstrate that protein tyrosine phosphatase activity in skeletal muscle is regulated by motoneurons.     

癫痫病人脑棘波灶轴突、突触和树突的病理学研究

目的研究癫痫病人脑棘波灶内轴突、突触和树突的病理学变化。方法癫痫患者29例,手术治疗时在皮层电图监测下取棘波灶大脑皮质,用βAPP、突触素和MAP2免疫组化方法,分别对轴突、突触和树突的病理变化进行研究,并对突触做了电镜观察。结果棘波灶内轴突病变不明显;突触分布不均,或密集成片,或稀疏淡染,电镜下轴棘非对称性突触前轴突末梢水肿,突触小泡减少或消失;树突屈曲变形,病变严重者树突变得粗细不均,或变成串珠状,多数树突失去分枝,血管周围树突排列紊乱。此外,在5例临床诊断为原发性癫痫的病例,观察到白质内神经细胞异位。结论癫痫棘波灶的病理变化主要发生在突触和树突,突触的增多、重组和丢失,以及白质神经细胞异位可能是癫痫异常放电的病理学基础。     

Imaging endogenous dopamine competition with [11C]raclopride in the human brain

This study images dopamine release in response to a neurochemically specific challenge with the psychostimulant drug methylphenidate. Changes in synaptic dopamine induced by methylphenidate were evaluated with positron emission tomography and [¹¹C]raclopride, a D₂ receptor radioligand that is sensitive to endogenous dopamine. Methylphenidate significantly decreased striatal [¹¹C]raclopride binding. The decrease was variable and was negatively correlated with age. Mood and anxiety at baseline, were also correlated with methylphenidate-induced DA changes. This strategy provides a tool to investigate the responsiveness of the dopamine system in the normal and diseased human brain and to investigate the neurochemical correlates of behavior. © 1994 Wiley-Liss, Inc.     

Pre- and postsynaptic actions of nifedipine at an identified cholinergic central synapse of Aplysia

The effects of the dihydropyridine (DHP) Ca²⁺ channel antagonist, nifedipine, were studied on the cholinergic synapse between the presynaptic neurones B4/B5 and the postsynaptic neurones B3/B6 located in the buccal ganglion of Aplysia californica. Nifedipine (10 M) decreased the presynaptic Ca²⁺ current by 30%–40%. Blockade of DHP-sensitive Ca²⁺ channels, however, did not affect quantal transmitter release from the presynaptic neurones. Thus, at this synapse, DHP-sensitive Ca²⁺ channels appear not to be involved in acetylcholine (ACh) release. The postsynaptic response to an ionophoretic application of ACh was decreased by nifedipine, pointing to a blocking action of the drug on the postsynaptic receptor/channel complex. Nifedipine was also found to activate protein kinase C, which in turn induces an increase in the nifedipine-resistant presynaptic Ca²⁺ influx and in the number of released ACh quanta. These effects of nifedipine could be prevented by a previous application of 1, 5-(isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), a protein kinase blocker.     

B lymphocyte activation during cognate interactions with CD4+ T lymphocytes: molecular dynamics and immunologic consequences

Productive interaction between T and B lymphocytes is required for humoral immune responses to many foreign protein antigens and production of pathogenic antibodies characteristic of several autoimmune conditions. Thus, much attention has been given in recent years to understand the dynamic molecular interactions and signal transduction required for productive T-B interaction. In this review we highlight current knowledge of signaling and biologic responses that occur in B cells during cognate interactions with helper T cells, focusing on the dynamic function of B cell-surface molecules in T-B synapses.     

Synapses in the granule cell layer of the rat dentate gyrus: serial-sectioning study

Synaptic contacts on the granule cell somata as well as on their axon initial segments in the dentate gyrus of one juvenile 5-week-old rat and one adult 12-week-old rat were analyzed in an electron microscopic serial-sectioning study. In the dentate gyrus of the juvenile rat, somata of 17 granule cells were nearly completely reconstructed from a series of 183 serial sections, and the axon initial segments of 15 of these granule cells were traced in various lengths. On the other hand, in the dentate gyrus of the adult rat, somata of 31 granule cells were almost completely reconstructed from a series of 238 serial sections, and the axon initial segments of 23 of these granule cells were traced in various lengths. Both symmetrical and asymmetrical synapses were observed on the somata, whereas almost all synapses on the axon initial segments were of symmetrical type and asymmetrical synapses on the axon initial segments were rather exceptional. Although we confirmed two conclusions from previous random-section studies to some extent, that is, the superficial-to-deep gradient of synaptic densities on granule cell somata and the presence of a substantial number of asymmetrical synapses on granule cell somata (about 23% of total somatic synapses), the present serial-sectioning study clearly revealed that granule cells vary greatly with regard to the number of synapses on their somata (15–186 in a 5-week-old rat and 9–144 in a 12-week-old rat) and axon initial segments. The granule cells also differed in the proportion of somatic asymmetrical synapses to total synapses they received (0–44% in a 5-week-old rat and 0–60% in a 12-week-old rat). The results of the present study indicated that, when a relatively small number of granule cells are analyzed, one should take the heterogeneity of synaptic contacts on granule cells in number and type into consideration.     

Spinal dis-inhibition in inflammatory pain

Inflammatory diseases and neuropathic insults trigger signaling cascades, which frequently lead to intense and long-lasting pain syndromes in affected patients. Such pain syndromes are characterized not only by an increased sensitivity to painful stimuli (hyperalgesia), but also by a qualitative change in the sensory perception of other, tactile stimuli (allodynia) and the occurrence of spontaneous pain in the absence of any sensory input. Long-term potentiation (LTP)-like changes in synaptic transmission between nociceptive C-fibers and spino-periaqueductal grey projection neurons as well as a loss of inhibitory control by GABAergic and glycinergic spinal dorsal horn neurons have repeatedly been proposed as underlying principles. While considerable evidence supports a significant contribution of C-fiber LTP to hyperalgesia, such monosynaptic plasticity cannot explain the occurrence of allodynia and spontaneous pain. In this review, we focus on mechanisms of synaptic dis-inhibition in inflammatory pain and propose that pathologically heightened pain sensitivity can be reversed by restoring synaptic inhibition with drugs that target specific spinal GABAA receptor subtypes.