Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy

Adrenalectomy of adult male rats resulted in a nearly complete loss of hippocampal granule cells 3 to 4 months after surgery. Nissl and immunocytochemical staining of hippocampal neurons revealed that the granule cell loss was selective; there was no apparent loss of hippocampal pyramidal cells or of gamma-amino butyric acid (GABA)-, somatostatin-, neuropeptide Y-, calcium binding protein-, or parvalbumin-containing hippocampal interneurons. The hippocampal CA1 pyramidal cells of adrenalectomized animals exhibited normal electrophysiological responses to afferent stimulation, whereas responses evoked in the dentate gyrus were severely attenuated. Corticosterone replacement prevented both the adrenalectomy-induced granule cell loss and the attenuated physiological response. Thus, the adrenal glands play a role in maintaining the structural integrity of the normal adult brain.     

Pattern separation in the dentate gyrus and CA3 of the hippocampus

Theoretical models have long pointed to the dentate gyrus as a possible source of neuronal pattern separation. In agreement with predictions from these models, we show that minimal changes in the shape of the environment in which rats are exploring can substantially alter correlated activity patterns among place-modulated granule cells in the dentate gyrus. When the environments are made more different, new cell populations are recruited in CA3 but not in the dentate gyrus. These results imply a dual mechanism for pattern separation in which signals from the entorhinal cortex can be decorrelated both by changes in coincidence patterns in the dentate gyrus and by recruitment of nonoverlapping cell assemblies in CA3.     

Requirement for hippocampal CA3 NMDA receptors in associative memory recall

Pattern completion, the ability to retrieve complete memories on the basis of incomplete sets of cues, is a crucial function of biological memory systems. The extensive recurrent connectivity of the CA3 area of hippocampus has led to suggestions that it might provide this function. We have tested this hypothesis by generating and analyzing a genetically engineered mouse strain in which the N-methyl-D-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice. The mutant mice normally acquired and retrieved spatial reference memory in the Morris water maze, but they were impaired in retrieving this memory when presented with a fraction of the original cues. Similarly, hippocampal CA1 pyramidal cells in mutant mice displayed normal place-related activity in a full-cue environment but showed a reduction in activity upon partial cue removal. These results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall.     

Unique processing during a period of high excitation/inhibition balance in adult-born neurons

The adult dentate gyrus generates new granule cells (GCs) that develop over several weeks and integrate into the preexisting network. Although adult hippocampal neurogenesis has been implicated in learning and memory, the specific role of new GCs remains unclear. We examined whether immature adult-born neurons contribute to information encoding. By combining calcium imaging and electrophysiology in acute slices, we found that weak afferent activity recruits few mature GCs while activating a substantial proportion of the immature neurons. These different activation thresholds are dictated by an enhanced excitation/inhibition balance transiently expressed in immature GCs. Immature GCs exhibit low input specificity that switches with time toward a highly specific responsiveness. Therefore, activity patterns entering the dentate gyrus can undergo differential decoding by a heterogeneous population of GCs originated at different times.     

Long-term potentiation in dentate gyrus: induction by asynchronous volleys in separate afferents

Long-term potentiation (LTP), a long-lasting enhancement of synaptic efficacy, is considered a model for learning and memory. In anesthetized rats, activation of dentate granule cells by stimulating either the medial or lateral perforant pathway at frequencies of 100 to 400 Hz produced LTP of the stimulated pathway preferentially at 400 Hz. However, hippocampal pathways do not normally fire at this high rate. Stimuli at 200 Hz were then applied to either the medial or lateral pathway separately, to both pathways simultaneously, or to the two pathways asynchronously so that the composite stimulus applied to the granule cell dendrite was 400 Hz. LTP was produced preferentially in the asynchronous condition. Thus, lower frequency, physiological input volleys arriving asynchronously at medial and lateral synapses can induce LTP by activating a 400-Hz sensitive mechanism capable of integrating spatially separated granule cell inputs. This may reflect how LTP is normally produced in the dentate gyrus.     

SAMP8小鼠衰老海马complexin含量呈环路特异性下降

利用免疫组化技术检测年龄对SAMP8小鼠海马突触前蛋白complexin1/2表达的影响。结果显示,与4.5月龄相比,13月龄组齿状回多形细胞层和外分子层及CA1区放射层的complexin1/2相对含量均显著下降,8月龄组后两者也下降。此外13月龄组CA3透明层complexin1/2低于表达较8月龄组。这些结果提示在SAMP8鼠海马complexin1/2含量随年龄增加而呈现环路特异性下降。     

青春期双酚A暴露对老年CD-1小鼠海马 齿状回Synaptotagmin 1含量的影响

探讨青春期双酚A暴露对老年期齿状回Synaptotagmin 1（Syt 1）含量的影响。结果显示,18月龄CD-1小鼠齿状回Syt 1相对含量显著高于6月龄小鼠（Ps<0.05）;青春期双酚A暴露高剂量小鼠齿状回Syt 1表达量显著高于同年龄对照小鼠（Ps<0.05）,雌鼠更明显。这些结果进一步支持小鼠海马Syt 1呈年龄相关性增加的结论,青春期双酚A暴露可加剧这种增加。     

胚胎晚期母体暴露细菌脂多糖对中年CD-1子鼠背海马synaptotagmi Ⅳ的影响

对胚胎晚期母体腹腔注射细菌脂多糖或生理盐水,利用免疫组化法对CD-1中年子鼠背海马CA1、CA3区和齿状回各层突触蛋白synaptotagmin IV的表达进行研究。结果显示synaptotagmin Ⅳ在背海马各层均有表达。与盐水对照组相比,细菌脂多糖处理组子鼠背海马CA1、CA3区各层和齿状回分子层的synaptotagmin Ⅳ含量显著增高(Ps<0.05)。结果表明胚胎晚期母体暴露细菌脂多糖可显著增加中年子鼠背海马Syt IV表达。     

Pattern separation in the human hippocampal CA3 and dentate gyrus

Pattern separation, the process of transforming similar representations or memories into highly dissimilar, nonoverlapping representations, is a key component of many functions ascribed to the hippocampus. Computational models have stressed the role of the hippocampus and, in particular, the dentate gyrus and its projections into the CA3 subregion in pattern separation. We used high-resolution (1.5-millimeter isotropic voxels) functional magnetic resonance imaging to measure brain activity during incidental memory encoding. Although activity consistent with a bias toward pattern completion was observed in CA1, the subiculum, and the entorhinal and parahippocampal cortices, activity consistent with a strong bias toward pattern separation was observed in, and limited to, the CA3/dentate gyrus. These results provide compelling evidence of a key role of the human CA3/dentate gyrus in pattern separation.     

仔猪神经干细胞体外培养及鉴定

由仔猪脑部海马体齿状回分离得到神经干细胞,利用无血清培养基添加特定生长因子方式培养;采用RT-PCR鉴定神经干细胞和诱导分化后细胞生物特性;利用免疫荧光化学技术检测克隆的细胞抗原和分化后特异性成熟神经细胞抗原表达。由海马体齿状回分离的细胞群具有连续克隆能力;根据免疫荧光检测,脑神经干细胞表达巢蛋白、配对盒因子6和解整合素样金属蛋白酶10;体外培养下NSCs可被诱导分化为神经源性细胞,且表达微管相关蛋白2、胶质纤维酸性蛋白和髓鞘碱性蛋白。分离和培育NSCs细胞结果显示,其具有更新能力和分化为神经元和胶质细胞的潜能,可为干细胞移植提供基础数据。     

中年CD-1小鼠背海马syntaxin 1水平的改变

应用免疫组化技术检测13月龄(中年)和5月龄CD-1小鼠背海马突触前蛋白syntaxin 1的表达水平.结果显示,13月龄小鼠齿状回、CA1及CA3区各层syntaxin 1的相对含量较5月龄均显著下降.表明中年CD-1小鼠背海马syntaxin 1含量全面下调.     

Expression of the beta-nerve growth factor gene in hippocampal neurons

In situ hybridization with complementary DNA probes for nerve growth factor (NGF) was used to identify cells containing NGF messenger RNA in rat and mouse brain. The most intense labeling occurred in hippocampus, where hybridizing neurons were found in the dentate gyrus and the pyramidal cell layer. The neuronal identity of NGF mRNA-containing cells was further assessed by a loss of NGF-hybridizing mRNA in hippocampal areas where neurons had been destroyed by kainic acid or colchicine. RNA blot analysis also revealed a considerable decrease in the level of NGF mRNA in rat dentate gyrus after a lesion was produced by colchicine. This lesion also caused a decrease in the level of Thy-1 mRNA and an increase in the level of glial fibrillary acidic protein mRNA. Neuronal death was thus associated with the disappearance of NGF mRNA. These results suggest a synthesis of NGF by neurons in the brain and imply that, in hippocampus, NGF influences NGF-sensitive neurons through neuron-to-neuron interactions.     

Comparison of two forms of long-term potentiation in single hippocampal neurons

In invertebrate nervous systems, some long-lasting increases in synaptic efficacy result from changes in the presynaptic cell. In the vertebrate nervous system, the best understood long-lasting change in synaptic strength is long-term potentiation (LTP) in the CA1 region of the hippocampus. Here the process is initiated postsynaptically, but the site of the persistent change is unresolved. Single CA3 hippocampal pyramidal cells receive excitatory inputs from associational-commissural fibers and from the mossy fibers of dentate granule cells and both pathways exhibit LTP. Although the induction of associational-commissural LTP requires in the postsynaptic cell N-methyl-D-aspartate (NMDA) receptor activation, membrane depolarization, and a rise in calcium, mossy fiber LTP does not. Paired-pulse facilitation, which is an index of increased transmitter release, is unaltered during associational-commissural LTP but is reduced during mossy fiber LTP. Thus, both the induction and the persistent change may be presynaptic in mossy fiber LTP but not in associational-commissural LTP.     

N-甲基-D-天门冬氨酸对鼠小脑颗粒细胞存活的影响

目的：研究N-甲基-D-天门冬氯酸(N-methyl-D-aspartate，NMDA)对鼠小脑颗粒细胞(CGC)存活的影响。方法：光镜观察NMDA和酒精对细胞所产生的作用。结果：NMDA在无酒精条件下促进细胞生存，并抑制酒精对细胞所产生的神经毒性作用而减少细胞死亡。结论：NMDA对小脑颗粒细胞具有神经营养和神经保护作用。     

MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity.

The role of major histocompatibility complex (MHC) class I expression in natural killer (NK) cell target recognition is controversial. Normal T cell blasts from MHC class I-deficient mutant mice were found to serve as target cells for NK cells in vitro, which suggests that MHC class I molecules are directly involved in NK cell recognition. Spleen cells from the mutant mice were deficient in their ability to lyse MHC class I-deficient target cells or NK-susceptible tumor targets, and mutant mice could not reject allogeneic bone marrow. Thus, class I molecules may participate in the positive selection or tolerance induction of NK cells.     

长期口服阿卡波糖对SAMP8小鼠背海 马synaptotagminⅠ的影响

利用免疫组化法检测长期口服阿卡波糖对SAMP8小鼠背海马突触蛋白synaptotagminⅠ（SytⅠ）表达的影响。结果显示,SytⅠ在背海马CA1、CA3区和齿状回各层均有表达。老年对照组小鼠背海马各区SytⅠ的相对含量显著高于青年对照组（Ps<0.05）。阿卡波糖处理组小鼠背海马各区SytⅠ的相对含量显著低于同龄对照组（Ps<0.05）。上述结果提示长期口服阿卡波糖可减轻SAMP8小鼠背海马年龄相关性SytⅠ增加的水平。     

Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning

The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway (which carries information as follows: entorhinal cortex --> dentate gyrus --> CA3 --> CA1 --> entorhinal cortex) and the monosynaptic pathway (entorhinal cortex --> CA1 --> entorhinal cortex). We developed a generally applicable tetanus toxin-based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in the trisynaptic pathway is dispensable and the short monosynaptic pathway is sufficient for incremental spatial learning. In contrast, the full trisynaptic pathway containing CA3 is required for rapid one-trial contextual learning, for pattern completion-based memory recall, and for spatial tuning of CA1 cells.     

Adenosine receptors: autoradiographic evidence for their location on axon terminals of excitatory neurons

Adenosine receptors were made visible on light microscopy by autoradiography with tritiated cyclohexyladenosine. In the cerebellum, adenosine receptors were absent in Weaver mice, which lack granule cells, and were displaced in Reeler mice, which have displacements of granule cells. Thus, adenosine receptors appear to be located on the axon terminals of excitatory granule cells in the cerebellum. Removal of one eye of a rat depleted adenosine receptors in the contralateral superior colliculus, suggesting that the receptors occur on axon terminals of excitatory projections from retinal ganglion cells. The presence of adenosine receptors on excitatory axon terminals may explain synaptic inhibition by adenosine and the behavioral effects of xanthines.     

死亡时间对雌性仔猪脑海马组织影响

为研究母猪脑海马死亡后变化情况,试验以同一遗传背景(杜×长×大)、体重及出生日龄相近的健康雌性仔猪作研究对象,采用核磁共振成像检测及光镜技术,检测母猪麻醉状态与死后10 min、1、2、3、6和10 h时段左侧、右侧海马体积,观察两侧海马齿状回区颗粒细胞形态,建立母猪死后海马形态学变化模型,为长期处于应激状态下妊娠母猪心理疾病的核磁共振诊断提供理论依据。核磁检测结果表明,仔猪死亡10 h内,与活体对照组海马体积比较,左侧海马体积无显著变化(P=0.901);右侧及总海马体积在死亡3 h内无显著性变化(右侧P=0.078;总P=0.104),但从死亡6 h开始显著变小(右侧P0.01;总P0.05);光镜观察表明,仔猪死亡3 h内,左侧及右侧海马齿状回区颗粒细胞形态与活体对照组相比,均未发生严重损害。死亡3 h内,仔猪脑海马组织无显著生理变化。     

Decreased neuronal inhibition in vitro after long-term administration of ethanol

The pathophysiology of brain dysfunction was studied with an animal model of chronic alcoholism. Rats were fed a liquid diet with or without ethanol for 20 weeks and then the diet without ethanol for three more weeks. Hippocampal slices were prepared and intracellular recordings were obtained from dentate granule and CA1 cells. Significant depression of orthodromically elicited inhibitory postsynaptic potentials and postspike afterhyperpolarizations was observed in neurons from ethanol-exposed animals. No differences were observed in other active or passive membrane characteristics. These results suggest that a loss of neuronal inhibition could contribute to brain dysfunction in chronic alcoholism.