Dendritic spikes and their inhibition in alligator Purkinje cells

Alligator Purkinje cells generate action potentials in the peripheral dendritic tree, after synaptic depolarization via superficial parallel fibers. These action potentials are inhibited at the dendrite level by preceding parallel-fiber volleys at close intervals. We conclude that this inhibition is produced by the activation of the inhibitory interneurons of the molecular layer, the stellate cells, which establish synaptic contacts with the dendrites of the Purkinje cells.     

Changes of simple and complex spike activity of cerebellar purkinje cells with sleep and waking

Action potentials of cerebellar Purkinje cells were observed in intact monkeys during sleep and waking. Purkinje cells exhibit two sorts of action potentials, called simple and complex spikes, and these two sorts of spikes were differently affected by sleep. Simple-spike activity (generated by the parallel fiber inputs to the Purkinje cell) was highest during sleep with rapid eye movements as compared with both waking and sleep with electroencephalographic slow waves. In contrast, complex-spike activity (generated by the climbing fiber inputs to the Purkinje cell) was lowest during sleep with rapid eye movements. The complex action potential of the Purkinje cell consists of an initial large spike followed by one or more smaller secondary spikes, and the number of these secondary spikes was found to be independent of the background discharge frequency of the simple spike. This independence suggests a possible role of presynaptic factors rather than the excitability level of the Purkinje cell itself in determining the number of secondary discharges occurring in the complex spike.     

Noradrenergic stimulation of cyclic adenosine monophosphate in rat Purkinje neurons: an immunocytochemical study

A specific immunofluorescent histochemical method for cyclic adenosine monophosphate was used to study rat cerebellum. After topical treatment with norepinephrine or stimulation of norepinephrine-containing afferents from locus coeruleus, there was a striking increase in the number of Purkinje cells with strong cyclic adenosine monophosphate reactivity. Other putative inhibitory transmitters had no significant effect on staining of Purkinje cells. The results provide the first histochemical support for the hypothesis that cyclic adenosine monophosphate can be generated postsynaptically in central neurons in response to noradrenergic stimuli.     

Preferred centripetal conduction of dendritic spikes in alligator Purkinje cells

Dendritic action potentials in alligator Purkinje cells tend to have a unidirectional preference which favors centripetal over centrifugal propagation. This unidirectional tendency funnels the peripherally evoked dendritic spikes into the lower dendrites and soma of these cells, and it allows the peripheral dendritic branches to operate to a certain extent as partially independent functional units.     

Dynamic organization of developing Purkinje cells revealed by transgene expression

The cerebellum has many properties that make it a useful model for investigating neural development. Purkinje cells, the major output neurons of the cerebellar cortex, have drawn special attention because of the availability of biochemical markers and mutants that affect their development. The spatial expression of L7, a protein specific for Purkinje cells, and L7 beta Gal, a gene expressed in transgenic mice that was constructed from the L7 promoter and the marker beta-galactosidase, delineated bands of Purkinje cells that increased in number during early postnatal development. Expression of the transgene in adult reeler mutant mice, which show inverted cortical lamination, and in primary culture showed that the initial expression of L7 is intrinsic to Purkinje cells and does not depend on extracellular signals. This may reflect an underlying developmental map in cerebellum.     

Excitatory and inhibitory effects of opiates in the rat vas deferens: a dual mechanism of opiate action

Both natural (-)-morphine and its unnatural enantiomer (+)-morphine exert an excitatory action on electrically stimulated contractions of rat vas deferens. Preexposure to (-)-morphine results in cross-tolerance to the inhibitory action of beta-endorphin. (-)-Naloxone and its stereoisomer (+)-naloxone also exert an excitatory action, but only (-)-naloxone bocks the inhibtory action of beta-endorphin. Thus morphine exerts a dual action on a peripheral organ: one an inhibitory action mediated by the stereospecific endorphin receptor that is blocked stereospecifically by naloxone, the other an excitatory action mediated by a nonstereospecific receptor that is not blocked by naloxone. The opiate abstinence syndrome is seen as due to the unmasking of the excitatory action of opiates when its concomitant inhibitory influence is removed by selective blockade by naloxone or weakened by selective tolerance. The view that the rat vas deferens is devoid of morphine receptors is now seen as arising from a reverse example of morphine's dual action: the masking of the inhibitory action of morphine by its concomitant and more potent excitatory action.     

Descending efferents from the superior colliculus relay integrated multisensory information

By means of their efferent projections to motor and premotor structures, the cells in the deep superior colliculus are intimately involved in behaviors that control the orientation of the eyes, pinnae, and head. These same efferent cells receive multiple sensory inputs, thereby apparently enabling an animal to orient its receptor organs in response to a wide variety of cues. This sensory convergence also provides a system in which motor responses need not be immutably linked to individual stimuli but can vary in reaction to the multitude of stimuli present in the environment at any given moment.     

出生前山羊小脑皮质神经元超微结构的观察

应用超薄切片技术研究了第6周到出生前山羊小脑皮质神经元超微结构发育的变化。结果表明:(1)出生前山羊小脑皮质内颗粒层细胞在第10周龄以前一直处于未分化状态,第10周龄以后开始分化,但直到出生前山羊小脑皮质内颗粒层细胞内细胞器的种类和数量都增加缓慢。(2)小脑浦肯野氏细胞在第7周龄以前处于未分化状态;在第7周龄开始分化,第7～14周龄处于不成熟期;第15～18周龄浦肯野氏细胞处于发育成熟期,细胞内各种细胞器均出现并充满整个胞体,细胞核膜趋于成熟,核内常染色质发达,中央核仁发育成熟;浦肯野氏细胞自第19周龄开始进入成熟期,细胞内尼氏小体开始形成并发育,但其体积较小,界限不明显,这表明浦肯野氏细胞在出生前尚未完全成熟,出生后仍存在一个较长生后发育过程。     

Parvalbumin in most gamma-aminobutyric acid-containing neurons of the rat cerebral cortex

gamma-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. In the cerebral cortex, GABA-containing cells represent a subpopulation of interneurons. With semithin frozen sections, it is possible to demonstrate that most GABA neurons in the rat somatosensory cortex contain the calcium-binding protein parvalbumin and that parvalbumin is found virtually only in GABA neurons. Parvalbumin seems to influence the electrical properties and enzymatic machinery to modulate neuronal excitability and activity. The specific role of parvalbumin in GABA-containing cortical cells may be related to controlling the effectiveness of their inhibitory action.     

betaAR signaling required for diet-induced thermogenesis and obesity resistance

Excessive caloric intake is thought to be sensed by the brain, which then activates thermogenesis as a means of preventing obesity. The sympathetic nervous system, through beta-adrenergic receptor (betaAR) action on target tissues, is likely the efferent arm of this homeostatic mechanism. To test this hypothesis, we created mice that lack the three known betaARs (beta-less mice). beta-less mice on a Chow diet had a reduced metabolic rate and were slightly obese. On a high-fat diet, beta-less mice, in contrast to wild-type mice, developed massive obesity that was due entirely to a failure of diet-induced thermogenesis. These findings establish that betaARs are necessary for diet-induced thermogenesis and that this efferent pathway plays a critical role in the body's defense against diet-induced obesity.     

茶氨酸溴香酰胺对人肝癌细胞体内外生长的抑制作用

以L-茶氨酸作对照,评估本实验室合成的新颖的茶氨酸衍生物-茶氨酸溴香酰胺（TBrC）对人肝癌HepG2细胞系体内外生长的抑制作用,并初步探究其作用的分子机制。采用MTT法检测不同浓度的TBrC对HepG2细胞体外生长的影响,应用蛋白质印迹法检测解析HepG2细胞中与癌细胞凋亡和生长密切相关蛋白的表达和药物可能作用的分子靶点。此外,建立动物肿瘤模型,与对照组茶氨酸和临床常用抗癌药物五氟尿嘧啶组相比较,评价TBrC对荷瘤裸鼠人肝癌HepG2肿瘤生长的抑制效果。实验结果显示,TBrC抑制人肝癌细胞体内外生长的活性超过其母体化合物茶氨酸分别为3倍和4倍以上,对小鼠生长无明显毒性。TBrC比茶氨酸更显著地抑制肝癌细胞生长因子受体c-Met和抗凋亡的Bcl-2等蛋白的表达;此外,TBrC大大上调促进凋亡的Bax蛋白的表达。TBrC抑制c-Met信号传导通路,下调Bcl-2/Bax蛋白比率可能是其作用的分子机制之一。这些结果提示,TBrC具有广泛应用于临床治疗和（或）辅助治疗人肝癌和其他癌症的潜力。     

Failure to confirm cyclic AMP as second messenger for norepinephrine in rat cerebellum

Microiontophoretic applications of adenosine 3',5'-monophosphate (cyclic AMP) to spontaneously active, electrophysiologically identified Purkinje cells of the rat cerebellum failed to mimic the strong depressant action of norepinephrine on the same cells. These findings, in combination with a reevaluation of other studies, cast doubt on the hypothesis that cyclic AMP mediates the depressant actions of norepinephrine in the cerebellum.     

Opposite synaptic actions mediated by different branches of an identifiable interneuron in Aplysia

Among the identifiable cells in the abdominal ganglion of Aplysia californica are five that generate bursting rhythms endogenous to the cells. In the four bursting cells of the left upper quadrant the rhythm is modulated by a unitary inhibitory postsynaptic potential; in the bursting cell of the right lower quadrant the rhythm is modulated by a unitary excitatory postsynaptic potential. Both the excitatory and inhibitory postsynaptic potentials are mediated by separate branches of a single interneuron. The pharmacological properties of the double action interneuron as well as those of the follower cells suggest that a single transmitter (acetylcholine) is involved in both the excitatory and the in-hibitory action of the interneuron.     

茶氨酸溴香酰胺对人宫颈癌细胞体内外生长的抑制作用

将茶氨酸为母体合成的茶氨酸衍生物茶氨酸溴香酰胺(TBrC)与茶氨酸作比较,评估茶氨酸溴香酰胺对人宫颈癌细胞体内外生长的抑制作用与其分子机制。应用MTT等方法检测不同浓度的TBrC对人宫颈癌细胞体外生长的影响,运用蛋白质印迹法检测解析这些人宫颈癌细胞中与凋亡和生长密切相关蛋白的表达和药物可能的作用靶点。此外,通过建立动物肿瘤模型,评价TBrC对荷瘤裸鼠人宫颈癌生长的抑制效果。实验结果显示,TBrC抑制人宫颈癌细胞体内外生长的活性超过其母体化合物茶氨酸多倍,对小鼠生长无明显毒性;TBrC作用的分子机制之一可能与抑制VEGFR1-Bcl-2/Bax信号传导通路相关。研究结果提示,TBrC具有广泛应用于临床治疗和(或)辅助治疗人宫颈癌和其他癌症的潜力。     

A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons

A genomic clone encoding the Purkinje cell-specific L7 protein has been isolated and utilized to drive the expression of beta-galactosidase in mice. Three independent transgenic lines, germ line transformed with an L7-beta-galactosidase fusion gene, exhibit beta-galactosidase expression in both cerebellar Purkinje cells and retinal bipolar neurons. This distribution is the same as that previously determined for the L7 protein by immunohistochemistry. The transgenic murine lines can be used to obtain populations of marked Purkinje and bipolar neurons. Similar L7 promoter constructs can be used to express other foreign genes specifically in these two classes of neurons.     

Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt

Extracellular signals often result in simultaneous activation of both the Raf-MEK-ERK and PI3K-Akt pathways (where ERK is extracellular-regulated kinase, MEK is mitogen-activated protein kinase or ERK kinase, and PI3K is phosphatidylinositol 3-kinase). However, these two signaling pathways were shown to exert opposing effects on muscle cell hypertrophy. Furthermore, the PI3K-Akt pathway was shown to inhibit the Raf-MEK-ERK pathway; this cross-regulation depended on the differentiation state of the cell: Akt activation inhibited the Raf-MEK-ERK pathway in differentiated myotubes, but not in their myoblast precursors. The stage-specific inhibitory action of Akt correlated with its stage-specific ability to form a complex with Raf, suggesting the existence of differentially expressed mediators of an inhibitory Akt-Raf complex.     

Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones

The production and action of immunoregulatory cytokines, including interleukin-1 (IL-1), are inhibited by glucocorticoid hormones in vivo and in vitro. Conversely, glucocorticoid blood levels were increased by factors released by human leukocytes exposed to Newcastle disease virus preparations. This activity was neutralized by an antibody to IL-1. Therefore the capacity of IL-1 to stimulate the pituitary-adrenal axis was tested. Administration of subpyrogenic doses of homogeneous human monocyte-derived IL-1 or the pI 7 form of human recombinant IL-1 to mice and rats increased blood levels of adrenocorticotropic hormone (ACTH) and glucocorticoids. Another monokine, tumor necrosis factor, and the lymphokines IL-2 and gamma-interferon had no such effects when administered in doses equivalent to or higher than those of IL-1. The stimulatory effect of IL-1 on the pituitary-adrenal axis seemed not to be mediated by the secondary release of products from mature T lymphocytes since IL-1 was endocrinologically active when injected into athymic nude mice. These results strongly support the existence of an immunoregulatory feedback circuit in which IL-1 acts as an afferent and glucocorticoid as an efferent hormonal signal.     

山核桃果皮提取物抗肿瘤活性研究

[目的]研究山核桃果皮提取物抗肿瘤活性。[方法]采用提取及萃取过程制备山核桃果皮提取物分离化合物,选取人肝癌SMMC-7721细胞及人宫颈癌Hela细胞为模型,测定山核桃果皮提取物对肿瘤细胞的抑制作用。[结果]从山核桃果皮所提取出的化合物具有一定的体外增殖抑制作用。[结论]山核桃果皮提取物是一种安全有效的抗肿瘤活性物质。     

Specialized inhibitory synaptic actions between nearby neocortical pyramidal neurons

We found that, in the mouse visual cortex, action potentials generated in a single layer-2/3 pyramidal (excitatory) neuron can reliably evoke large, constant-latency inhibitory postsynaptic currents in other nearby pyramidal cells. This effect is mediated by axo-axonic ionotropic glutamate receptor-mediated excitation of the nerve terminals of inhibitory interneurons, which connect to the target pyramidal cells. Therefore, individual cortical excitatory neurons can generate inhibition independently from the somatic firing of inhibitory interneurons.