下丘脑—脊髓直接投射及神经内分泌整合作用

1930年Beattie用神经纤维溃变法首次揭示下丘脑到脊髓的直接纤维投射(HSP)。1975年以来Kuypers等许多作者利用HRP、放射自显影及免疫组化的方法在各种不同的动物证实了上述重要结论。另有不少学者用电刺激结合脑区切割或HRP法探索下丘脑—脊髓通路的功能意义,但尚未获得有关HSP的生理学证据。HSP通路可能使下丘脑对脊髓自主中枢的管理更加迅捷有效,并影响痛觉传入,而室旁核(PVH)则可能是下丘脑实现神经内分泌整合功能的重要脑区。     

下丘脑—脊髓直接投射及神经内分泌整合作用

1930年 Beattie 用神经纤维溃变法首次揭示下丘脑到脊髓的直接纤维投射(HSP). 1975年以来 Kuypers 等许多作者利用 HRP、放射自显影及免疫组化的方法在各种不同的动物证实了上述重要结论.另有不少学者用电刺激结合脑区切割或 HRP 法探索下丘脑—脊髓通路的功能意义,但尚未获得有关 HSP 的生理学证据. HSP 通路可能使下丘脑对脊髓自主中枢的管理更加迅捷有效,并影响痛觉传入,而室旁核(PVH)则可能是下丘脑实现神经内分泌整合功能的重要脑区.     

孤束核参与刺激下丘脑室旁核的镇痛作用

本实验用电刺激鼠尾-嘶叫法测痛,观察电刺激下丘脑室旁核的镇痛效应,并采用核团损毁和核团内微量注射药物等方法分析其镇痛通路。实验结果如下:(1)电刺激下丘脑室旁核能产生明显的镇痛效应。同时,放射免疫测定发现脑干加压素含量升高。(2)损毁孤束核能取消刺激下丘脑室旁核的镇痛效应,但对基础痛阈无影响。(3)孤束核内微量注射加压素拮抗剂[d(CH_2)_5 TYr(Me)-AVP]60ng/0.6μl 和加压素抗血清0.6μl 都可明显对抗刺激下丘脑室旁核的镇痛效应。(4)直接在孤束核内微量注射加压素60ng/0.6μl,能模拟刺激下丘脑室旁核的镇痛效应。实验结果表明:电刺激下丘脑室旁核能产生镇痛效应,其机理之一可能是兴奋了下丘脑室旁核中加压素能神经元胞体,后者通过下行投射纤维在孤束核中释放加压素,影响孤束核神经元的活动,从而产生镇痛。     

下丘脑室旁核参与脑刺激镇痛的实验研究

目的 :探讨下丘脑室旁核 (PVN )的镇痛与脑刺激镇痛间的关系及作用途径。方法 :用 4%水合氯醛麻醉大鼠 ,在PVN埋藏双极刺激电极或不锈钢管 ,在中缝大核 (NRM )埋藏损毁电极 ,并暴露脊髓用玻璃微电极记录脊髓背角神经元对伤害刺激坐骨神经的反应 ,信号由计算机采集处理。结果 :电解中缝大核 (NRM )后 ,刺激PVN可抑制脊髓背角神经元伤害反应 ,其作用时间持续 15～18min ,其中 3～ 6min抑制作用最强 ;向PVN微量注射吗啡 10 μg ,脊髓背角神经元伤害单位放电明显减少 ,纳洛酮可反转吗啡的抑制作用。结论 :PVN除通过已知的内源性镇痛系统中的NRM中继外 ,也可能通过PVN 脊髓背角间的直接神经投射等途径参与脑刺激镇痛 ,此作用过程中在PVN可能有吗啡参与。本工作对痛觉生理及镇痛的研究具有重要意义。     

单胺类受体阻断剂和纳洛酮对家兔脊髓下行性抑制作用的影响

实验在27只麻痹的清醒家兔上进行。用玻璃微电极记录丘脑束旁核单位对腓总神经伤害性刺激发生的痛敏放电情况。这种痛敏放电活动均能无例外地被模拟的下行性抑制、即用弱电流刺激分离的脊髓背侧1/2外周端所抑制。在27个单位中,静注α-肾上腺能受体阻断剂酚妥拉明后,有16个单位的脊髓刺激的抑制效应被明显削弱,11个单位的脊髓刺激效应基本无变化。在5个酚妥拉明有效的单位,待药物作用消失之后,其脊髓刺激效应均能被纳洛酮所阻断。在5个脊髓刺激效应不受酚妥拉明影响的单位,静注5-羟色胺受体阻断剂賽庚啶后,有4个单位的脊髓刺激效应被明显削弱;而另外一个单位的脊髓刺激效应依然存在。以上实验结果提示,经由脊髓背侧下行、在脊髓水平对痛信号进行调制的下行通路可能主要包括两类纤维系统,一类以去甲肾上腺素(通过α受体发挥作用)和内源性吗啡样物质为递质或/和调制物,另一类则以-5羟色胺为递质。这两类纤维可能分别影响不同的脊髓背角上行投射神经元。     

中枢肾素-血管紧张素-醛固酮系统在慢性心衰时对交感神经活动的影响

交感神经活动增强是加重慢性心力衰竭的一个重要因素.神经解剖学证实脊髓交感节前神经元直接接受来自下丘脑室旁核和延髓头端腹外侧区神经元纤维的投射,心衰时这两个区域体液因子的改变明显影响外周交感神经放电,因此许多从事心衰研究的学者将目光转向了中枢神经系统.目前,该领域的研究尚处于起步阶段,相关研究的报道较少,但中枢肾素-血管紧张素-醛固酮系统促进交感神经活动进而加重心衰的观点被多数人所支持.本文就这些方面做一综述.     

鸣禽欧椋鸟带状核的传出投射—PHAL顺行示踪法研究

本实验应用顺行神经示踪物ＰＨＡＬ对鸣禽欧椋鸟（Ｓｔｕｒｎｕｓ ｖｕｌｇａｒｉｓ）带状核（Ｔｎ）的传出投射作了定位研究。Ｔｎ核的传出投射经背腹两条路线：（１）从Ｔｎ核背部进入端脑的ＰＨＡＬ标记纤维,分别终止在新纹状体内侧,隔内侧核（ＳＭ）,侧室腔外侧带和额上层腹侧带;（２）另一组标记纤维从Ｔｎ核腹侧直接向丘脑投射,在下丘脑腹内侧核（ＶＭＮ）和外侧核（ＬＨｙ）分别获得大量ＰＨＡＬ免疫反应纤维的终末标记。结果提示：Ｔｎ核可能为鸟类旁听觉神经通路的一个组成部分。     

犬脊髓损伤治疗动物模型

目的　建立犬脊髓损伤治疗动物模型 ,为实验研究提供直接的病例材料。方法　人工损伤犬脊髓 ,使用直流电场刺激使脊髓损伤恢复。结果　人工犬脊髓损伤模型建立 ,直流电场刺激治疗可恢复神经功能。结论直流电场刺激在不同时期对犬脊髓再生及功能恢复均有明显促进作用 ,能促进脊髓再生 ,使脊髓通路更快更完善的建立     

人参茎叶皂甙对大鼠垂体催乳素分泌的影响及其机制的探讨

本实验观察了人参茎叶皂甙(GSLS)对雄性大鼠血浆催乳素水平、垂体催乳素细胞超微结构和下丘脑中枢神经递质的影响。结果表明:5～100mg/kg的GSLS可刺激催乳素的释放,剂量加大反而无效;GSLS还可拮抗急性饥饿所致的大鼠垂体催乳素细胞超微结构的损伤;GSLS能分别使大鼠下丘脑中多巴胺和5-羟色胺含量增高和降低。结果表明,GSLS有刺激垂体催乳素分泌的作用,其机制可能与其直接作用于垂体细胞和/或经下丘脑中多巴胺和5-羟色胺含量的变化有关。     

心血管生理的进展——参加第三十届国际生理科学大会札记

在这次大会上,有关心血管生理的内容较多,现就较重要的几个方面,作一简介。一、心血管活动的神经调节腹外侧延髓在心血管活动调节中的作用,近年来已日益引起重视。Caver-son 等观察到,腹外侧延髓头端的加压区神经元,直接投射到脊髓内的交感区,并接受下丘脑和外周心血管感受器来的传入信息,从而参与循环控制的整合机制。在腹外侧延髓已找到一些单位,其轴突直达孤束     

ELECTROPHYSIOLOGICAL MEASURES OF AUDITORY PROCESSING IN ODONTOCETES

ABSTRACT

The preponderance of our knowledge concerning hearing in the Cetacea has come from psychophysical studies. The most widely used alternative to psychophysical studies are neurophysiological studies utilizing auditory evoked potentials (AEPs). Due in part to the hypertrophy of auditory structures exhibited by the Cetacea, AEPs are highly robust and rapidly and easily obtained. Moreover, because AEPs reflect the synchronized activity of large neuronal assemblies, they offer a high level window onto auditory processing and allow for across-species comparison of responses.

Recent studies utilizing AEP techniques have demonstrated that the cetaceans have extremely high temporal resolution with integration times in the order of 300 msec. Remarkably, these animals also exhibit extremely sharp frequency tuning with auditory filters having Q10 of 20–30.     

Optimal (‘Wiener’) digital filtering of auditory evoked potentials: use of coherence estimates

Auditory evoked potentials (AEPs) to 40 Hz clicks and amplitude-modulated 500 Hz tones in human subjects were digitally filtered using an optimal (‘Wiener’) filter uniquely determined for each AEP. Use of coherence functions to compute coefficients appropriate for filtering grand average AEPs or subsets such as split-half averages is described. Wiener-filtered AEPs correlated better than unfiltered AEPs with split-half replicates and with references AEPs (obtained with long data collection periods). Visual detection thresholds were lower (more sensitive) for the Wiener-filtered AEPs, but not as low as objectively determined thresholds using coherence values.     

Otoacoustic emissions,auditory evoked potentials and self-reported gender in people affected by disorders of sex development (DSD)

Both otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) are sexually dimorphic, and both are believed to be influenced by prenatal androgen exposure. OAEs and AEPs were collected from people affected by 1 of 3 categories of disorders of sex development (DSD) — (1) women with complete androgen insensitivity syndrome (CAIS); (2) women with congenital adrenal hyperplasia (CAH); and (3) individuals with 46,XY DSD including prenatal androgen exposure who developed a male gender despite initial rearing as females (men with DSD). Gender identity (GI) and role (GR) were measured both retrospectively and at the time of study participation, using standardized questionnaires. The main objective of this study was to determine if patterns of OAEs and AEPs correlate with gender in people affected by DSD and in controls. A second objective was to assess if OAE and AEP patterns differed according to degrees of prenatal androgen exposure across groups. Control males, men with DSD, and women with CAH produced fewer spontaneous OAEs (SOAEs) – the male-typical pattern – than control females and women with CAIS. Additionally, the number of SOAEs produced correlated with gender development across all groups tested. Although some sex differences in AEPs were observed between control males and females, AEP measures did not correlate with gender development, nor did they vary according to degrees of prenatal androgen exposure, among people with DSD. Thus, OAEs, but not AEPs, may prove useful as bioassays for assessing early brain exposure to androgens and predicting gender development in people with DSD.     

Effects of GSM signals on auditory evoked responses

The article presents a study of the influence of radio frequency (RF) fields emitted by mobile phones on human cerebral activity. Our work was based on the study of Auditory Evoked Potentials (AEPs) recorded on the scalp of healthy humans and epileptic patients. The protocol allowed us to compare AEPs recorded with or without exposure to RFs. To get a reference, a control session was also introduced. In this study, the correlation coefficients computed between AEPs, as well as the correlation coefficients between spectra of AEPs were investigated to detect a possible difference due to RFs. A difference in the correlation coefficients computed in control and experimental sessions was observed, but it was difficult to deduce the effect of RFs on human health.     

Activation of duration-sensitive auditory cortical fields in humans

The influence of stimulus duration on auditory evoked potentials (AEPs) was examined for tones varying randomly in duration, location, and frequency in an auditory selective attention task. Stimulus duration effects were isolated as duration difference waves by subtracting AEPs to short duration tones from AEPs to longer duration tones of identical location, frequency and rise time. This analysis revealed that AEP components generally increased in amplitude and decreased in latency with increments in signal duration, with evidence of longer temporal integration times for lower frequency tones. Different temporal integration functions were seen for different N1 subcomponents. The results suggest that different auditory cortical areas have different temporal integration times, and that these functions vary as a function of tone frequency.     

Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: structural insights and new members

We report an in-depth computational study of the protein sequences and structures of the superfamily of archaeo-eukaryotic primases (AEPs). This analysis greatly expands the range of diversity of the AEPs and reveals the unique active site shared by all members of this superfamily. In particular, it is shown that eukaryotic nucleo-cytoplasmic large DNA viruses, including poxviruses, asfarviruses, iridoviruses, phycodnaviruses and the mimivirus, encode AEPs of a distinct family, which also includes the herpesvirus primases whose relationship to AEPs has not been recognized previously. Many eukaryotic genomes, including chordates and plants, encode previously uncharacterized homologs of these predicted viral primases, which might be involved in novel DNA repair pathways. At a deeper level of evolutionary connections, structural comparisons indicate that AEPs, the nucleases involved in the initiation of rolling circle replication in plasmids and viruses, and origin-binding domains of papilloma and polyoma viruses evolved from a common ancestral protein that might have been involved in a protein-priming mechanism of initiation of DNA replication. Contextual analysis of multidomain protein architectures and gene neighborhoods in prokaryotes and viruses reveals remarkable parallels between AEPs and the unrelated DnaG-type primases, in particular, tight associations with the same repertoire of helicases. These observations point to a functional equivalence of the two classes of primases, which seem to have repeatedly displaced each other in various extrachromosomal replicons.     

The macrocyclizing protease butelase 1 remains autocatalytic and reveals the structural basis for ligase activity

Plant asparaginyl endopeptidases (AEPs) are expressed as inactive zymogens that perform maturation of seed storage protein upon cleavage‐dependent autoactivation in the low‐pH environment of storage vacuoles. The AEPs have attracted attention for their macrocyclization reactions, and have been classified as cleavage or ligation specialists. However, we have recently shown that the ability of AEPs to produce either cyclic or acyclic products can be altered by mutations to the active site region, and that several AEPs are capable of macrocyclization given favorable pH conditions. One AEP extracted from Clitoria ternatea seeds (butelase 1) is classified as a ligase rather than a protease, presenting an opportunity to test for loss of cleavage activity. Here, making recombinant butelase 1 and rescuing an Arabidopsis thaliana mutant lacking AEP, we show that butelase 1 retains cleavage functions in vitro and in vivo. The in vivo rescue was incomplete, consistent with some trade‐off for butelase 1 specialization toward macrocyclization. Its crystal structure showed an active site with only subtle differences from cleaving AEPs, suggesting the many differences in its peptide‐binding region are the source of its efficient macrocyclization. All considered, it seems that either butelase 1 has not fully specialized or a requirement for autocatalytic cleavage is an evolutionary constraint upon macrocyclizing AEPs.     

Impaired attentional modulation of auditory evoked potentials in N-methyl-D-aspartate NR1 hypomorphic mice

In human neurophysiology, auditory event-related potentials (AEPs) are used to investigate cognitive processes such as selective attention. Selective attention to specific tones causes a negative enhancement of AEPs known as processing negativity (PN), which is reduced in patients with schizophrenia. The evidence suggests that impaired selective attention in these patients may partially depend on deficient N-methyl-D-aspartate receptor (NMDAR)-mediated signaling. The goal of this study was to corroborate the involvement of the NMDAR in selective attention using a mouse model. To this end, we first investigated the presence of PN-like activity in C57BL/6J mice by recording AEPs during a fear-conditioning paradigm. Two alternating trains of tones, differing in stimulus duration, were presented on 7 subsequent days. One group received a mild foot shock delivered within the presentation of one train (conditioning train) on days 3-5 (conditioning days), while controls were never shocked. The fear-conditioned group (n= 9) indeed showed a PN-like activity during conditioning days manifested as a significant positive enhancement in the AEPs to the stimuli in the conditioning train that was not observed in the controls. The same paradigm was then applied to mice with reduced expression of the NMDAR1 (NR1) subunit and to a wild-type control group (each group n= 6). The NR1 mutants showed an associative AEP enhancement, but its magnitude was significantly reduced as compared with the magnitude in wild-type mice. We conclude that electrophysiological manifestations of selective attention are observable yet of different polarity in mice and that they require intact NMDAR-mediated signaling. Thus, deficient NMDAR functioning may contribute to abnormal selective attention in schizophrenia.     

Temporal Feature Perception in Cochlear Implant Users

For the perception of timbre of a musical instrument, the attack time is known to hold crucial information. The first 50 to 150 ms of sound onset reflect the excitation mechanism, which generates the sound. Since auditory processing and music perception in particular are known to be hampered in cochlear implant (CI) users, we conducted an electroencephalography (EEG) study with an oddball paradigm to evaluate the processing of small differences in musical sound onset. The first 60 ms of a cornet sound were manipulated in order to examine whether these differences are detected by CI users and normal-hearing controls (NH controls), as revealed by auditory evoked potentials (AEPs). Our analysis focused on the N1 as an exogenous component known to reflect physical stimuli properties as well as on the P2 and the Mismatch Negativity (MMN). Our results revealed different N1 latencies as well as P2 amplitudes and latencies for the onset manipulations in both groups. An MMN could be elicited only in the NH control group. Together with additional findings that suggest an impact of musical training on CI users’ AEPs, our findings support the view that impaired timbre perception in CI users is at partly due to altered sound onset feature detection.     

Correlation of evoked potentials in the frontal cortex and hippocampus of cats in emotional stress

Averaged auditory evoked potentials (AEPs) were recorded in symmetric points of the frontal cortex and dorsal hippocampus of cats performing acquired conditioned food-procuring reaction reinforced in 100% cases, urgent transition to 30%-reinforcement, and return to 100%-reinforcement. Emotional stress estimated by a heart rate rise developed during increased food motivation of a cat as well as during change in ordinary food-procuring stereotype. The emotional stress was accompanied by a high positive correlation of cortical and hippocampal AEPs. Decrease in the stress level led to a drop between AEP correlations and appearance of their negative values. In emotional stress, the interactions between the frontal cortex and dorsal hippocampus were asymmetric: right-side correlations were higher.