食物奖赏和渴求行为相关的大鼠左侧眶额叶皮质Delta频段脑电活动(英文）

眶额叶皮质与中脑边缘多巴胺奖赏系统有着复杂的相互纤维联系。先前的研究探讨了药物成瘾过程中眶额叶皮质的脑电活动。在本实验中,将探讨食物奖赏和渴求过程中该皮质的脑电活动。实验采用了两个环境：对照环境和食物刺激相关的环境。首先,训练大鼠在食物刺激相关的环境中吃巧克力花生豆,而后在该环境中设置两种不同的刺激方式：能看到和闻到但不能吃到(渴求实验),或者仍旧可以吃到巧克力花生豆（奖赏实验）;同时进行左侧眶额叶皮质的脑电记录。结果发现,在食物刺激相关的环境中大鼠Delta频段（2－4 Hz）的脑电活动与食物刺激显著相关,此外,与在对照环境中相比,其相对功率在食物渴求时下降而在食物奖赏时升高。本实验表明,食物相关的奖励可以改变大鼠眶额叶皮质的脑电活动,而且,Delta频段的脑电活动能够作为监测该奖励的一个指标。     

大鼠眶额叶皮质受损破坏新异性探索行为

利用旷场测试和Y-迷宫测试两种行为模型检测了双侧眶额叶（orbitofrontal cortex, OFC）电损伤或假损伤雄性SD大鼠的新异性探索行为, 探讨了OFC在大鼠探索新异环境中的作用。旷场测试的结果发现,OFC损伤大鼠的行走距离和直立次数较假损组有明显降低;同时,在Y-迷宫测试中与假损伤组大鼠相比,OFC损伤大鼠在新异臂的访问时间和穿梭次数明显降低。提示眶额叶皮质在大鼠新异性探索行为中起着重要作用。     

内侧前额叶皮质DNA甲基化调控大鼠酒精相关行为

酒精滥用不仅导致组织器官损伤,还易诱发神经精神疾病。研究表明,DNA甲基化在酒精诱导基因表达和行为改变中发挥重要作用,但具体的神经生物学机制尚未被阐明。为了探索DNA甲基化在酒精滥用中的作用机制,本研究选取健康成年雄性SD大鼠(Rattus norvegicus)32只,随机分为饮水对照组(n=16)和慢性酒精暴露组(n=16),运用双瓶选择实验(two bottle choice test,TBCT)评估大鼠酒精偏爱率(alcohol preference),通过旷场行为(open field test,OFT)评估活动状态并检测血酒精浓度。分离两组大鼠内侧前额叶皮质(medial prefrontal cortex,mPFC),提取总DNA,利用简化代表性重亚硫酸盐测序技术(reduced representation bisulfite sequencing,RRBS)构建mPFC甲基化谱,对差异基因进行功能富集和通路分析,筛选与酒精滥用密切相关的甲基化差异基因,运用qRT-PCR技术检测差异基因的表达,验证DNA甲基化对基因的表达调控;利用qRT-PCR和Western blot检测甲基转移酶(DNA methyltransferases,DNMTs)和甲基化CpG位点结合蛋白2(methyl CpG binding protein 2,MeCP2)的表达;同时,还检测了短期酒精暴露(7 d)对大鼠mPFC内DNMTs和MeCP2的影响(n=8/组)。结果表明,慢性酒精暴露大鼠mPFC内基因启动子区甲基化水平显著升高。与酒精滥用密切相关的差异基因中,慢性酒精暴露组Ntf3和Ppm1G启动子区甲基化水平升高,mRNA表达降低;Hap1和DUSP1启动子区甲基化水平降低,mRNA表达升高。慢性酒精暴露使DNMT3B和MeCP2 mRNA和蛋白表达升高,而短期内酒精暴露不影响它们的表达。本研究初步证实DNA甲基化与酒精滥用的发展相关,可能受DNMT3B和MeCP2分子的调控,并发现了与酒精滥用相关的靶基因Ntf3、Ppm1G、Hap1和DUSP1,为研究酒精滥用的神经生物学机制提供了新见解,同时为酒精滥用治疗提供了可能的药理学靶点。     

电针对氯胺酮成瘾大鼠内侧前额叶皮质酪氨酸羟化酶表达的影响

目的观察不同时辰电针“足三里”和“三阴交”穴对氯胺酮成瘾大鼠内侧前额叶皮质（mPFC）酪氨酸羟化酶（TH）表达的影响,探讨电针治疗氯胺酮滥用成瘾的作用机制。方法将56只SD大鼠随机分为正常对照组、生理盐水对照组、模型组、电针治疗组,电针治疗组再分为子时（23：00）、卯时（05：00）、午时（11：00）、酉时（17：00）4个电针组,每组8只。每天1次经腹腔注射氯胺酮复制氯胺酮成瘾模型,不同时辰电针组在给药7d后分别选取一侧“足三里”和“三阴交”穴给予低频（2Hz）电针治疗,每次30min,连续治疗7d。采用免疫组织化学染色方法检测mPFC内TH的表达。结果与正常对照组和生理盐水对照组相比较,模型组mPFC内TH免疫反应阳性神经元的数量明显增多（P〈0．01）,细胞平均灰度值降低（P〈0．01）,与模型组相比较,午时、酉时电针组TH免疫反应阳性神经元的数量明显减少（P〈0．01）,细胞平均灰度值升高（P〈0．01）;子时、卯时电针组则无明显变化（P〉0．05）。结论氯胺酮成瘾使mPFC内TH的表达明显增加;午时、酉时电针“足三里”和“三阴交”穴可明显下调mPFC内TH的表达,改善氯胺酮成瘾症状。     

电刺激大鼠内侧额叶前皮质对听皮层神经元频率感受野可塑性的调制

本文应用常规电生理学技术,研究电刺激大鼠内侧额叶前皮质（medial prefrontal cortex,mPFC）对初级听皮层神经元频率感受野（receptive field,RF）可塑性的调制。电刺激mPFC,137个听皮层神经元（72．8％）RF可塑性受到影响,其中抑制性调制71个神经元（37．7％）,易化性调制66个神经元（35．1％）,其余51个神经元（27．2％）不受影响。mPFC的抑制性调制效应表现为,RF的偏移时间延长,恢复时间缩短。相反,mPFC的易化性调制效应表现为,RF的偏移时间缩短,恢复时间延长。电刺激mPFC对RF可塑性的调制与声、电刺激之间的时间间隔有关,最佳时间间隔介于5-30ms之间。结果提示,大鼠mPFC可以调制听皮层神经元的功能活动,可能参与听觉学习记忆过程。     

慢性吗啡处理及戒断对社会新颖性和食物寻求行为的影响（英文）

阿片肽在调控社会性和非社会性天然奖赏中具有重要作用。寻求天然奖赏的动机与动物的情绪状态有关。吗啡注射和戒断会引起动物不同的情绪状态。本研究探讨了吗啡处理期和戒断期是否会影响动物对2种类型天然奖赏(社会新颖性和食物)的寻求行为。雄性小鼠连续注射14 d的吗啡(10 mg·kg~(-1),生理盐水作对照组),在最后一次注射20 min后,依次检测了小鼠的运动性及对熟悉个体、陌生个体和食物的接近时间。戒断7 d后,以上行为变量(除运动性)被再次检测。结果表明,盐水处理及戒断的小鼠对陌生个体的接近时间明显多于熟悉个体,且表现出对食物的偏好。吗啡处理的小鼠运动性增加,接近陌生个体和熟悉个体的时间差异无统计学意义,但仍表现出对食物的偏好。与盐水组相比,吗啡戒断降低了小鼠对食物的偏好,但不影响对陌生个体的接近时间。这些结果表明,吗啡会损害寻求社会新颖性和食物的动机;慢性吗啡处理和戒断对这2种天然奖赏的寻求行为有不同的影响,这种差异可能与吗啡经验诱导的不同神经适应有关。     

Stimulation of Fructose-1,6-Biphosphatase Activity and Synthesis in the Cerebral Cortex of Rats Submitted to the Convulsant Methionine Sulfoximine

Purification of rat cerebral cortex fructose-1,6-biphosphatase (FBPase) was performed by substrate elution from phosphocellulose, followed by Sephadex G-200 column filtration. The purified enzyme exhibited an optimum at pH 7.5, and its catalytic properties were very similar to those of the purified whole-brain enzyme previously prepared by Majumder and Eisenberg in 1977. The isolated preparation was electrophoretically homogeneous. The molecular weight of the enzyme subunit was 40,000; the hydrophobic amino acids predominated with 592 residues, and tryptophan was not detected. Expressed as mumol fructose-1,6-biphosphate hydrolysed per g brain tissue wet weight per min, FBPase activity increased twofold 24 h after an intraperitoneal injection of 100 mg per kg body weight of the convulsant methionine sulfoximine (MSO); the increase of the rate of incorporation of [1-14C]valine into brain FBPase was 2.8-fold under the same experimental conditions. A rabbit specific antiserum against rat cerebral cortex FBPase was prepared, and immunotitration studies confirmed both an increase in the number of molecules and the activation of brain FBPase, 24 h after administration of MSO. The increase of the number of brain FBPase molecules, induced by MSO, was due to an increase in synthesis of the enzyme, as shown by a double-label valine incorporation study.     

Neuronal Activity Preceding Directional and Nondirectional Cues in the Premotor Cortex of Rhesus Monkeys

Pre-cue activity, the neuronal modulation that precedes a predictable stimulus, was studied in the premotor cortex of three rhesus monkeys. In one condition, a directional cue dictated the timing and target of a forelimb movement. In another condition, a non-directional cue provided identical timing information but did not indicate the target. Of 501 task-related neurons recorded in premotor cortex, 168 showed pre-cue activity. The onset time of pre-cue activity varied markedly from trial to trial and cell to cell, ranging from trial initiation to 4.8 sec later. No pre-cue activity reflected the direction of limb movement; thus, the data argue against the hypothesis that pre-cue activity reflects preparation for specific limb movements. A small number of cells showed greater pre-cue activity before directional than before nondirectional cues, and this difference may reflect anticipation of the cue's directional information. However, the vast majority (84%) of neurons lacked such differences. We therefore hypothesize that most pre-cue activity reflects or contributes to a facet of behavior common to the two conditions: anticipation of the time and/or nature of events.     

Modifications of EEG Related to Directed Perception and Analysis of Olfactory Information in Humans

We recorded EEG in adult volunteers in the course of perception of smells of plant essential oils under conditions of directed attention. It was found that perception of olfactory information, even in the case of mild intensity of the smells inducing no aversive effects, correlates with noticeable changes in the EEG characteristics mostly typical of the reaction of nonspecific EEG activation induced by sensory stimulation and manifested in a decrease in the spectral power, SP, of low-frequency EEG components (6–10 Hz)). In addition, the SP of relatively high-frequency EEG components (11–25 Hz) increased; this effect was most pronounced in the occipital regions of the neocortex. Perception of the smells of essential oils was also accompanied by increases in the coherence of EEG oscillations, most intense in the β2 range (20–25 Hz). Such modifications were maximum in the left temporal/parietal region; this is interpreted as an indication of the special role of these cortical areas in the processes of interaction between the neocortical part of the olfactory analyzer and the respective structures of other analyzer systems. It is hypothesized that such interaction is necessary for the formation of a semantic image of the analyzed stimuli. Neirofiziologiya/Neurophysiology, Vol. 41, No. 1, pp. 70–78, January–February, 2009.     

大鼠大脑皮层中钙调神经磷酸酶活力的时空变化

以ＰＮＰＰ为底物测定了超离心制备的大鼠出生后早期和成年大脑皮层亚细胞各组分中钙调神经磷酸酶的活力。实验结果表明：（ｌ）钙调神经磷酸酶活力广泛地存在于胞液和突触部分,并且各亚细胞组分有明显差异。成年大鼠大脑皮层中ＣａＮ活力相对最高水平是在突触体,突触质,胞液,重的和轻的突触膜部分。（２）大鼠大脑皮层突触体中ＣａＮ活力在出生后第２周和第３周出现高峰的平台期,这与突触发生的高峰期是一致的。在胞液和重的突触膜中ＣａＮ活力最高水平是在出生后的第７ｄ,而在突触质和轻的突触膜中是在第２０ｄ。总之,这些发现证实,在脑发育期间,ＣａＮ活力是依照区域和时间性控制的,提示ＣａＮ可能参与了突触功能作用。     

幼年大鼠视皮层神经元对闪光刺激的反应特性

哺乳动物视觉系统的发育延续到出生后,大鼠出生后 3~5 周是视觉系统发育的关键期 . 在关键期中,视皮层的兴奋性和抑制性突触连接逐渐成熟,形成有效的皮层内回路 . 为了观察发育关键期大鼠视皮层神经元的反应特性与成年大鼠的异同,使用胞外单细胞记录的方法对比研究了幼年和成年大鼠对闪光刺激的视觉反应特性 . 结果显示：与成年大鼠相比较,幼年大鼠视皮层神经元对持续闪光刺激显示出更强的适应性,对光刺激的诱发放电频率更低,而在没有光刺激时的自发放电频率更高,从而导致信噪比更低 . 这一结果表明,幼年大鼠视皮层对连续刺激的反应能力下降,对信号的分辨能力也更弱,其原因可能是兴奋性突触和抑制性突触发育的不同步所致 .     

Set-Related Activity in the Premotor Cortex of Rhesus Monkeys: Effect of Triggering Cues and Relatively Long Delay Intervals

“Set-related activity” has been defined as a significant alteration in neuronal discharge rate during an “instructed delay period,” a period when a previously instructed movement is being withheld. It has been argued that set-related activity in the primate premotor cortex, or at least a significant proportion of it, reflects motor preparation. In most previous investigations, however, in which visual stimuli have triggered the movement and simultaneously indicated its target, set-related activity might reflect either the anticipation of or attention to the trigger stimulus. The present report shows that set-related activity is robust and can be directionally selective when trigger stimuli do not indicate the target and when a trigger stimulus is absent. Another feature of previous studies has been the relatively brief intervals between the instruction and trigger stimuli (typically 3 sec or less). In the present study, we were able to observe the activity of a small number of cells during longer delay periods. Set-related activity persists, although it becomes less consistent, for as much as 7.5 sec after an instruction stimulus. These results support the hypothesis that set-related activity reflects the preparation for specific limb movements.     

Serotonin Metabolism and Release in Frontal Cortex of Rats on a Vitamin E-Deficient Diet

Abstract: Rats were fed a control or vitamin E (all- rac -α-tocopheryl acetate)-deficient diet for 3 or 12 weeks. Serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan, and α-tocopherol concentrations were determined in the frontal cortex using HPLC. α-Tocopherol concentrations fell significantly to 27% of control values at 12 weeks. Tissue 5-HT, 5-HIAA, and tryptophan concentrations were not significantly altered by the vitamin E-deficient diet at either time point. In vivo microdialysis revealed normal basal and K⁺-stimulated concentrations of 5-HT and 5-HIAA, but extracellular concentrations of tryptophan were significantly decreased after 3 weeks on the vitamin E-deficient diet, which resulted in an increase in the tissue/extracellular ratio and suggested a change in compartmentation. However, after 12 weeks on the deficient diet these values had returned to normal. Results in general indicate that a prolonged and substantial depletion of brain vitamin E can occur without major disturbance of serotonergic function.     

多巴胺D2受体拮抗剂、激动剂对SD大鼠条件化位置偏好的影响

通过慢性吗啡处理方式建立起SD大鼠吗啡依赖的条件化位置偏好(CPP)模型,用行为学手段研究多巴胺(DA)D2受体拮抗剂及激动剂对SD大鼠CPP的影响,探讨眶额叶DAD2受体在阿片精神依赖中的作用。通过腹腔注射吗啡同环境因素相结合,建立大鼠吗啡依赖的CPP模型;采用局部脑内微量注射法向额叶注射DAD2受体拮抗剂或激动剂或盐水(对照组),以得到SD大鼠在戒断期间的CPP的时间数据。CPP显示DAD2受体拮抗剂组与对照组相比,从戒断第2天起,前者表现出更明显的CPP增加现象,差异显著(P<0·05)。而DAD2受体激动剂组与对照组相比无显著差异(P>0·05)。采用腹腔小剂量注射吗啡,成功地建立了吗啡依赖SD大鼠的CPP模型;眶额叶微量注射DAD2受体拮抗剂增加了CPP时间,提示眶额叶多巴胺系统在吗啡依赖的过程中有着较为重要的作用;也提示了对于已经成瘾的动物,损伤其眶额叶,会使药物渴求增强。因而提示对于药物依赖患者进行手术干预治疗要极其慎重。