Prior information and oculomotor initiation: the effect of cues in gaps

Eye movements reflect not only an important output of various neural control systems, but also often reflect cognitive processing. For example, saccades are frequently used as a behavioural index of attentional processing. A second important eye movement type, smooth pursuit (SP), has received much less attention in this regard. These two types of eye movement were classically thought of as being separate, but recent results have suggested a closer linkage of their control mechanisms and perhaps their interactions with cognitive processes. Prior information, in the form of cues, alters saccade latency leading to characteristic cueing effects. When the period between the appearance of the cue and the appearance of the saccade target is sufficiently long, the latency of saccades to targets appearing at cued locations is increased. This "inhibition of return" is enhanced by a second type of stimulus manipulation, the early removal of the fixation target a few hundred milliseconds before the target appears (the gap paradigm). In the current experiments, the effect of cues, and interactions between cues and long gaps were investigated. In the main pursuit experiment, and in a separate saccade experiment, subjects were presented with interleaved runs of tasks with and without long gaps (gap duration = 1 s), and with and without cues. In tasks without cues, SP latency was reduced by long gaps (mean reduction 8 ms); unexpectedly, saccade latency for non-cue tasks was increased by long gaps (mean increase 41 ms). In a control experiment with only non-cue tasks, in which SP and saccade gap and non-gap tasks were run together, SP latency was again reduced in gap tasks, while saccade latency was increased, but by much less than in the first experiment. Analysis of individual subjects' data showed that while gaps increased saccade latency in two subjects who had participated in the main experiment (in which cues and gaps had been combined), in two naive subjects long gaps did not affect saccade latency. In the main pursuit experiment, cues had both spatially specific and non-spatially specific (warning) effects on pursuit latency. In non-gap conditions, latency was greater when contralateral cues were presented 250 ms prior to the appearance of the pursuit target, compared to ipsilateral cues, a pattern of effect consistent with inhibition of return. However, this was reversed when cues appeared during a gap--contralateral cues increased while ipsilateral cues decreased latency. For saccades, as expected, in both gap and non-gap conditions, cue effects were consistent with inhibition of return (latency was lower with contralateral cues), and the inhibition of return effect was larger in gap, compared to non-gap conditions. The results suggest that, in appropriate contexts (or as a result of appropriate training), there are distinct inhibitory mechanisms that operate on saccades but not pursuit. What appears to be an inhibition of return effect on pursuit latency when static cues are presented in pursuit tasks, may be better understood as the product of a modulation of mechanisms active in pursuit initiation, perhaps related to motion processing. In contrast to some recent evidence suggesting a close anatomical and functional linkage between pursuit and saccade initiation, the results are consistent with the involvement of a wider range of mechanisms, or a greater degree of flexibility, in programming the initiation of these two oculomotor behaviours.     

三磷酸腺苷对人横纹肌肉瘤细胞系诱导分化作用的研究

为了探讨三磷酸腺苷（ＡＴＰ０对人横纹肌肉瘤细胞增殖和分化的影响，用ＡＴＰ作用于人横纹肌肉瘤细胞亚系（ＲＤＬ６）细胞，观察到ＡＴＰ可抑制ＲＤＬ６细胞的增殖，使其生长速度明显减慢，作用第５ｄ时增殖抑制率为８１％，流式光度术检测；观察到ＡＴＰ ＲＤＬ６细胞Ｓ期的细胞数明显增多，说明细胞停滞在Ｓ期，用罗氏黄荧光染料传法实，ＡＴ家恢复ＲＤＬ６细胞间隙加接通讯功能的作用。用 光细胞化学方法观察到经ＡＴＰ处理后     

Stochastic and Coherence Resonance in an In Silico Neural Model

We show that it is possible for chaotic systems to display the main features of stochastic and coherence resonance. In particular, a model of coupled nonlinear oscillators which emulates the transmembrane voltage activities in CA3 neurons, operating in a chaotic regime and in the presence of noise, can exhibit coherence resonance and stochastic resonance. Certain firing frequencies become more "rhythmic" for some optimal values of noise intensity. The effect of noise in different coupling pathways is investigated. We found that the effect of coherence resonance and stochastic resonance are more prominent if noise is presented in either electric field or gap junction coupling pathways. Frequency sensitivity of the model is investigated as a preliminary step in illustrating the principles of possible epileptic seizure control strategies using "chaos control" concepts. Significant effects of stochastic resonance are observed in the 4-8 Hz range. Weaker effects can be found in the 1-4 Hz and 8-10 Hz ranges whereas 0.5 Hz does not exhibit any resonance phenomenon. Our results suggest that: (a) Stochastic resonance could enhance the intrinsic 4-8 Hz rhythms in CA3 neurons more prominently via field coupling pathways. It could also help explain why some reported seizure control strategies using pulse-trains would only be effective at 0.5 Hz. (b) Stochastic resonance-like behavior can occur in the gamma range only if noise is presented via chemical synaptic pathways.     

缝隙连接蛋白在钙离子介导的乳腺癌细胞转移和侵袭中的作用

目的 探讨缝隙接蛋白(Cx)在钙离子介导的乳腺癌细胞转移和侵袭中的作用. 方法 选用不影响细胞生长的缝隙连接蛋白阻断剂,辛醇100μmol/L处理高转移MDA-MB-231细胞和低转移MCF-7细胞.倒置相差显微镜下观察细胞形态,激光扫描共焦显微镜下观察Cx43的位置、微丝纤维的排列和细胞内钙离子浓度变化,划痕和侵袭实验观察细胞的转移情况. 结果 辛醇处理细胞后,细胞的生长状态由大面积片状生长转变为单个或少数几个团状的独立生长;Cx43蛋白的形成和表达位置虽无改变,但相邻细胞间微丝纤维排列的平行同向性显著性降低;MDA-MB-231细胞穿过基底膜成胶和Transwell小室基底面的细胞数显著低于对照组;此外,细胞内钙离子浓度强度显著性降低,钙离子螯合剂(EGTA)处理显著性加剧辛醇对细胞转移和侵袭能力的抑制.但是,上述现象在低转移MCF-7细胞中效果不明显.结论 缝隙连接蛋白阻断剂在干扰乳腺癌细胞Cx功能活性,而不影响Cx形成的情况下,能够显著性抑制高转移乳腺癌的恶性进展和侵袭转移,此机制与细胞内钙离子浓度降低有关.     

Gating of cx46 gap junction hemichannels by calcium and voltage

 Connexin 46 (cx46), when expressed in Xenopus oocytes, not only forms typical gap junction channels between paired cells but also forms open gap junction hemichannels in the plasma membrane of single cells. The gap junction hemichannels share properties with complete gap junction channels in terms of permeability and gating. Here we characterize the gate that closes hemichannels in response to increased calcium concentration with whole-cell and single-channel records. The channels close within a narrow range of extracellular calcium concentrations (1–2 mM) which includes the calcium concentration prevailing in the primary site of cx46 expression, the lens. The effect of calcium on the channels is determined by voltage. A cysteine mutant of cx46, cx46L35C, was used to determine the localization of the gate. Experimental evidence suggests that position 35 is pore lining. The localization protocol tests the accessibility of position 35 for thiol reagents applied extra- or intracellularly to the channel closed by calcium. Channel closure by calcium excluded the thiol reagent from the outside but not from the inside. Consequently, the gate results in a regional closure of the pore and it is located extracellular to the position 35 of cx46. The present data also suggest that the cx46 gap junction hemichannel may exert a physiological function in the lens. Considering the association of calcium with cataract formation, it is feasible that misregulation of cx46 gap junction hemichannels could be a cause for cataract. Received: 30 July 1998 / Received after revision and accepted: 14 September 1998     

大鼠骨髓间质干细胞体外诱导分化为心肌样细胞Cx43通讯连接功能检测

目的： 探讨大鼠骨髓间充质干细胞（MSCs）体外诱导分化为心肌样细胞Cx43的分布与通讯连接功能状态。方法： 取健康SD大鼠骨髓，用5-氮杂胞苷体外诱导培养。取诱导培养2、3、4周的MSCs为Ⅰ、Ⅱ、Ⅲ组，另取急性分离的心肌细胞为对照组，用激光共聚焦技术检测Cx43的分布及平均荧光漂白恢复率。结果： 对Cx43在细胞内分布检测发现，随诱导培养时间的延长，细胞内蛋白颗粒密度逐渐增加；诱导培养4周后MSCs内蛋白颗粒密度与对照组比较无显著差异（63.87±12.43，64.87±12.15，P>0.05）。各组细胞平均荧光漂白率的变化趋势与Cx43分布变化相似，即随诱导培养时间的延长，细胞平均荧光漂白率逐渐增加；Ⅰ、Ⅱ、Ⅲ组及对照组分别为19.59%±6.08%、37.17%±3.84%、46.82%±2.69%、49.71%±5.53%，Ⅲ组与对照组比较无显著差异（P>0.05）。结论： 大鼠MSCs在体外诱导培养4周后已分化为心肌样细胞，其细胞Cx43的分布与通讯连接功能与正常心肌细胞相似。     

胆红素和内毒素联合作用对NRK52E细胞缝隙连接功能的影响

目的: 观察胆红素(BR)和内毒素(LPS)联合作用对肾小管上皮细胞(NRK52E)生长及细胞间缝隙连接(GJ)的影响。方法: 体外培养NRK52E细胞,不同浓度的BR和LPS联合干预,用MTT测量细胞生长;观察它们对生长融合细胞(有GJ形成)和生长未融合细胞(无GJ形成)集落形成的影响;采用细胞荧光免疫示踪法分析细胞间GJ的功能。结果: BR 从17.1 μmol/L增加至 513 μmol/L,可浓度依赖性地增加细胞生长;当BR浓度继续增加时,细胞生长逐渐降低。LPS(10-1 000 μg/L)能浓度依赖性地降低NRK52E细胞生长。 BR和LPS 联合作用下,513 μmol/L BR增加100 μg/L LPS作用下的细胞生长(P<0.05),而684 μmol/L BR降低100 μg/L LPS的细胞生长(P<0.05);513 μmol/L BR能增加100 μg/L LPS作用下GJ传递数目(P<0.05),684 μmol/L BR降低100 μg/L LPS作用下的GJ传递数目。 结论: BR和LPS联合作用时,513 μmol/L BR降低LPS的细胞毒性,684 μmol/L BR增加LPS的细胞毒性,其改变可能是通过细胞间缝隙连接发挥作用的。     

芹黄素提高胸苷激酶基因系统治疗前列腺癌疗效的研究

目的　观察芹黄素 (apigenin)对前列腺癌 (PC)细胞PC 3m生长的影响及其对单纯疱疹胸苷激酶 /更昔洛韦 (HSV tk/GCV)系统“旁观者效应”的调控 ,寻求增强该系统对PCa疗效的途径。方法　四甲基偶氮唑盐比色法 (MTT法 )检测 1、10、10 0 μmol/Lapigenin对PC 3m细胞生长的影响 ,观察 10 μmol/Lapigenin预处理后GCV对tk基因阳性 (tk+ )比例为 10 %和 5 %的混合细胞的杀伤作用及 18 α 甘草次酸 ( 18 α glycyrrhetinicacidAGA)对其影响 ,并检测apigenin联合GCV的杀伤效应。结果　Apigenin可抑制PCa细胞增殖 ,呈时间和剂量依赖关系 (P <0 .0 5 0 ) ;低浓度( 10 μmol/L) apigenin预处理对PC 3m细胞增殖无影响但可使“旁观者效应”明显增强 (P <0 .0 0 1) ,10 μmol/L和 10 0 μmol/LGCV对tk+ 为 10 %细胞的杀伤率由 ( 16.15± 1.64 ) %和 ( 2 3 .46± 3 .2 1) %提高到 ( 4 5 .89± 3 .2 8) %和 ( 5 9.86± 2 .44 ) % ,该作用可被AGA抵消。联合应用apigenin和GCV后杀伤率更为显著 ,达 ( 62 .5 8± 4.2 9) %和 ( 83 .16± 3 .72 ) %。结论　Apigenin不仅可以直接杀伤PC细胞 ,还可通过增强HSV tk/GCV系统“旁观者效应” ,发挥间接杀瘤效应 ,从而提高该系统治疗PC疗效。     

Temperature dependence of gap junction properties in neonatal rat heart cells

Cell pairs of neonatal rat hearts were used to study the influence of temperature on the electrical properties of gap junctions. A dual voltage-clamp method was adopted, which allowed the voltage gradient between the cells to be controlled and the intercellular current flow to be measured. Cell pairs with normal coupling revealed a positive correlation between the conductance of the junctional membranes, g _j, and temperature. Cooling from 37° C to 14° C led to a steeper decrease in g _j, cooling from 14° C to -2° C to a shallower decrease (37° C: g _j=48.3 nS; 14° C: g _j=21.4 nS;-2°C: g _j=17.5 nS), corresponding to a temperature coefficient, Q ₁₀, of 1.43 and 1.14 respectively. The existence of two Q ₁₀ values implies that g _j may be controlled by enzymatic reactions. When g _j was low, i. e. below 5 nS (conditions: low temperature; treatment with 3 mM heptanol), it showed voltage-dependent gating. This property was not visible when g _j was large, i. e. 20–70 nS (conditions: high temperature; normal saline), presumably because of series resistances (pipette resistance). Cell pairs with weak intrinsic coupling and normally coupled cell pairs treated with 3 mM heptanol revealed a positive correlation between the conductance of single gap-junction channels, _j, and temperature (37° C: 75.6 pS; -2°C: 19.6 pS), corresponding to a Q ₁₀ of 1.41.     

Gap Junctions Couple Astrocytes and Oligodendrocytes

In vertebrates, a family of related proteins called connexins form gap junctions (GJs), which are intercellular channels. In the central nervous system (CNS), GJs couple oligodendrocytes and astrocytes (O/A junctions) and adjacent astrocytes (A/A junctions), but not adjacent oligodendrocytes, forming a “glial syncytium.” Oligodendrocytes and astrocytes each express different connexins. Mutations of these connexin genes demonstrate that the proper functioning of myelin and oligodendrocytes requires the expression of these connexins. The physiological function of O/A and A/A junctions, however, remains to be illuminated.