秀丽线虫记忆的分子调控机制

模式无脊椎动物秀丽线虫已经成为揭示记忆复杂行为的理想研究模型之一.线虫具有三种简单的记忆形式对温度感知的记忆、对化学物质感知的记忆以及对于机械刺激感知的记忆.在对机械刺激感知的记忆研究中,短时程、中时程与长时程记忆均得到了系统的分析.其中短时程与中时程记忆可能定位于感觉神经元的前突触,而长时程记忆可能定位于中间神经元的后突触.本文针对线虫中记忆的遗传与分子调控机制近些年的研究进展进行了总结与讨论.     

Evaluation of the long-term memory for thermosensation regulated by neuronal calcium sensor-1 in Caenorhabditis elegans

Objective To evaluate whether the thermotaxis tracking model is suitable for assessing long-term memory （LTM） in the nematode Caenorhabditis elegans. Methods Animals were trained at 20℃ overnight in presence of food. The percentage of animals performing isothermal tracking （IT） behavior was measured at different time intervals after the training. Results The percentage of animals performing IT behavior, the numbers of body bends inside and outside the training temperature, and the expression patterns of AFD and AIY neurons were similar to those in control animals at 36 and 48 h after training; whereas when extending to 60, 72, and 84 h, locomotory behavior defects were observed in the assayed animals, suggesting that this thermal tracking model is feasible for analyzing LTM at 36 and 48 h after training. Moreover, the percent-age of animals performing IT behavior was reduced at 18, 36, and 48 h after training in neuronal calcium sensor-1 gene （nsc-1） mutant animals compared with that in wild-type N2 animals. In addition, exposure to plumbum （Pb） significantly repressed the LTM at 18, 36, and 48 h after training in both wild-type N2 and ncs-1 mutant animals. Conclusion The thermotaxis tracking model is suitable for evaluating the LTM regulated by NCS-1, and can be employed for elucidating regulatory functions of specific genes or effects of stimuli on memory in C. elegans.     

Localization of neuronal calcium sensor-1 at the adult and developing rat neuromuscular junction

Neuronal calcium sensor (NCS-1; frequenin) is a calcium-binding protein involved in the regulation of neurotransmission in the central and peripheral nervous systems from insects to vertebrates. This study reports the localization of NCS-1 immunoreactivity, by Western blotting and immunohistochemistry, at the adult and developing postnatal rat neuromuscular junction. Our confocal immunofluorescence results on the whole-mount muscle and on semithin cross-sections are indicative of the localization of NCS-1 to motor axon terminals. There is no evidence of immunoreactivity in the postsynaptic side of the neuromuscular junctions or teloglial Schwann cells. These results suggest that NCS-1 is involved in the formation and function of presynaptic nerve terminal part of the neuromuscular junction during synaptogenesis and in adult mammals.     

The connectome of the Caenorhabditis elegans pharynx

Detailed anatomical maps of individual organs and entire animals have served as invaluable entry points for ensuing dissection of their evolution, development, and function. The pharynx of the nematode Caenorhabditis elegans is a simple neuromuscular organ with a self-contained, autonomously acting nervous system, composed of 20 neurons that fall into 14 anatomically distinct types. Using serial electron micrograph (EM) reconstruction, we re-evaluate here the connectome of the pharyngeal nervous system, providing a novel and more detailed view of its structure and predicted function. Contrasting the previous classification of pharyngeal neurons into distinct inter- and motor neuron classes, we provide evidence that most pharyngeal neurons are also likely sensory neurons and most, if not all, pharyngeal neurons also classify as motor neurons. Together with the extensive cross-connectivity among pharyngeal neurons, which is more widespread than previously realized, the sensory-motor characteristics of most neurons define a shallow network architecture of the pharyngeal connectome. Network analysis reveals that the patterns of neuronal connections are organized into putative computational modules that reflect the known functional domains of the pharynx. Compared with the somatic nervous system, pharyngeal neurons both physically associate with a larger fraction of their neighbors and create synapses with a greater proportion of their neighbors. We speculate that the overall architecture of the pharyngeal nervous system may be reminiscent of the architecture of ancestral, primitive nervous systems.     

Expression and possible role of neuronal calcium sensor-1 in the cerebellum

Neuronal calcium sensor-1 (NCS-1) is a member of EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. In this mini-review, we first summarize distribution of NCS-1 in the cerebellum. NCS-1 is mainly detected in postsynaptic sites, such as somata and dendrites of Purkinje cells, stellate/basket cells and granule cells. In addition, GABAergic inhibitory stellate/basket cell axon terminals also contain NCS-1. Secondly, we describe cerebellar compartmentation defined by NCS-1. The NCS-1 immunostaining displayed characteristic parasagittal-banding pattern in the Purkinje cell layer and molecular layer, whereas there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate/basket cells were uniformly NCS-1-positive throughout the cerebellum. Interestingly, NCS-1 and zebrin II exhibited a similar parasagittal-banding pattern. But it is noteworthy that NCS-1-negative/zebrin II-positive Purkinje cell clusters were detected selectively in anterior lobule vermis and paraflocculus. These results suggest that NCS-1 defines a novel pattern of cerebellar cortical compartmentation. Lastly, we describe recent data suggesting some relationship between NCS-1 and cerebellar long-term depression-related molecules, and discuss the possible role of NCS-1 in the cerebellum.     

Differential expression of neuronal calcium sensor-1 in the developing chick retina

Neuronal calcium sensor-1 (NCS-1) is a Ca(2+) binding protein that has been implicated in the regulation of neurotransmission and synaptogenesis. In this study we investigated the developmental expression and localization of NCS-1 in the chick retina. Single- and double-labeling experiments with three-dimensional reconstruction as well as ultrastructural data of the distribution of NCS-1 suggest that this protein is also involved in axonal process outgrowth. We found an early expression of NCS-1 in ganglion cells and their axons, in amacrine, and in horizontal cells, whereas photoreceptors were immunonegative at embryonic stages. In the early posthatching days we found strong immunostaining for NCS-1 in horizontal cells and their processes in the outer plexiform layer. In contrast, synaptic vesicle protein 2 (SV2) was prominent only in photoreceptor synaptic terminals. Ultrastructural analysis confirmed that NCS-1 was localized postsynaptically in horizontal cell processes, whereas presynaptic terminals were immunonegative. However, at late posthatching days we observed that photoreceptor ribbon synapses (from rods and/or cones) also expressed NCS-1. Thus the results support the notion that NCS-1 is involved in neuronal process outgrowth and is localized in pre- and postsynaptic compartments including mature photoreceptor synapses.     

模式动物线虫的学习与学习抉择行为

线虫因为其简单的体系和对于诸如接触、味道、气味和温度等外界刺激的敏感反映能力,日益成为受人瞩目的研究行为可塑性的模式动物。目前认为,线虫中的学习包括非联想与联想学习两大类,且存在至少6种形式化学趋向性介导的联想学习。同时,三种研究体系已经被开发出来用于学习抉择的研究。本文讨论了线虫中学习与学习抉择的形式、研究模型及其遗传与分子调控机制。     

模式动物线虫的学习与学习抉择行为(英文)

线虫因为其简单的体系和对于诸如接触、味道、气味和温度等外界刺激的敏感反映能力,日益成为受人瞩目的研究行为可塑性的模式动物。目前认为,线虫中的学习包括非联想与联想学习两大类,且存在至少6种形式化学趋向性介导的联想学习。同时,三种研究体系已经被开发出来用于学习抉择的研究。本文讨论了线虫中学习与学习抉择的形式、研究模型及其遗传与分子调控机制。     

Compartmentation of the mouse cerebellar cortex by neuronal calcium sensor-1

Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. The detailed distribution of NCS-1 was analyzed in the mouse cerebellar cortex. In coronal sections, the NCS-1 immunostaining displayed characteristic parasagittal banding pattern in the Purkinje cell layer and molecular layer, while there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate-basket cells were uniformly NCS-1-positive throughout the cerebellum. Immunofluorescent double staining showed that NCS-1 and zebrin II exhibited a similar parasagittal banding pattern. Then, we performed mapping of NCS-1- and/or zebrin II-labeled Purkinje cell somata using seven sequential coronal sections. NCS-1-positive/zebrin II-positive Purkinje cell clusters were seen throughout the cerebellum, but NCS-1-positive/zebrin II-negative Purkinje cells were exceedingly rare. On the other hand, NCS-1-negative/zebrin II-positive Purkinje cell clusters were found in anterior lobule vermis and paraflocculus, whereas they were rarely seen in posterior lobules. The digitized quantitative analysis showed close relationship between NCS-1 and zebrin II immunoreactivity in the molecular layer. The correspondence between NCS-1 and zebrin II demonstrated here indicates a novel anteroposterior difference of cerebellar compartmentation and provides fundamental information of cerebellar organization.