与作业无关的新异刺激对猕猴额叶神经元延缓期反应的作用

在猕猴执行延缓辨别作业和单纯辨别作业时,观察了与作业无关的新异刺激对额叶神经元延缓期放电的影响。在这两种作业中,延缓期在1—4s之间随机变化。此时,动物必须高度注意信号的变化,稍不注意即导致操作错误。此外,在延缓辨别作业中,动物在延缓期还要暂时记住暗示期的信号,单纯辨别作业则无此要求。在203个与作业相关的神经元中,有70个神经元在延缓期出现放电频率变化,其中见于延缓辨别作业者41个,见于单纯辨别作业者29个。实验结果表明,在这两种作业的延缓期所出现的神经元放电增多的反应,有着许多相同的特点。与课题无关的声、光、触、痛等刺激引起分心时,神经元的延缓期反应出现明显的变化,随之出现操作错误。多数神经元的反应受到抑制,但也有出现反应增强者,而且同一神经元对不同感觉模式的无关刺激可出现不同的效应,表现出不同程度的感觉模式特异性。此外,无关刺激在延缓期和在测试间歇期可产生不同甚至相反的效应。上述在延缓期出现反应的神经元主要位于额叶弓状沟上支内侧部的一定范围内。本文对实验结果进行了讨论,认为额叶神经元的延缓期反应,可能在很大程度上与注意有关。额叶神经元感觉模式各种程度的特异性可能是注意的通道选择性的神经基础。额叶的背内侧部,包括前额叶后部和运动前区前部     

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 .     

猕猴前额叶皮层神经元在视觉延缓分辨活动中的放电活动

在已学会颜色延缓分辨的3只猕猴上,用钨丝微电极记录前额叶背外侧部皮层神经元的放电活动,着重分析神经元放电活动与颜色延缓分辨活动的各个时期之间的相互关系。延缓分辨任务开始时,同时把红色光和绿色光分别投射在测试板上的两个显示窗上,约持续1.2s(暗示期)。颜色光熄灭后2—4s(此为延缓期),各自位于每一显示窗下的两个反应键同时向猴方推出。自此,反应期开始,动物应马上有选择地作出按键反应。如果动物作出正确选择按红色光下的反应键,则给少量桔子汁作奖励。共记录了155个前额皮层单位。其中40个单位的放电频率在动物完成视觉延缓分辨作业过程中没有明显变化,另外115个单位与该任务的某些时期有关。大多数单位(n=99)在反应键推出时,或者在按反应键的前后有放电频率变化。这99个单位中,15个在暗示期和反应期内放电活动有变化(CR 型单位),13个在延缓期和反应期内放电活动有变化(DR 型单位),42个只在反应期内或反应期后放电频率出现变化(R 型单位),其余29个单位则在分辨任务的各个时期都显示出放电活动变化(CDR 型单位)。上述这些单位中,有少数单位在动物作出正确反应时的放电型式与动物作出错误反应时的放电型式有明显不同。此外,即使动物对任务测试不作出按键反应时,也观察到16个单位的放电活动在任     

猕猴执行痛、热延缓辨别作业时额叶神经元及肌电活动的观察

为研究额叶神经元对躯体痛、热刺激出现反应的机能意义,设计了痛、热延缓辨别作业对猕猴进行实验。痛和热仅在暗示期给予,要求动物对此不立即作出行为反应。而是暂时记住这个信号,等到行动期再作出反应。待作业正确率连续三天达90%以上,记录额叶神经元和两侧上肢肌肉的电活动.以观察神经元活动与信号刺激以及肌肉活动之间的关系。在记录的142个作业相关神经元中,与痛、热刺激相关者87个(66.4%)。其中22个仅对痛刺激、18个仅对热刺激起反应,47个对痛、热刺激都起反应(其中4个反应方向相反)。此外,有21个对痛、热、视都出现反应。其余仅对视觉刺激起反应。这些神经元主要位于额叶弓状沟上支内侧,包括前额叶和运动前区皮层。在两侧上肢12块肌肉中,除操作侧指总伸肌、尺侧腕屈肌和桡侧腕屈肌在压放杠杆时,可记录到短暂的肌电活动外,在作业的其它时期和其它肌肉均未记录到规律的肌电活动。这表明痛热刺激在暗示期引起的神经元反应与行为动作的发动没有直接关系,从而支持关于额叶皮层这一区域的神经元在对刺激物信号意义的辨别机制中,可能起着重要作用的假说。     

在延缓分辨作业的学习过程中猕猴大脑皮层慢电位的变化

本工作在两只猕猴上记录了在延缓分辨作业不同训练阶段的皮层慢电位变化,分辨作业模型与前文报道的相同^[1],延缓分辨行为建立后,在额奁的许多部位都能记录到负的慢电位变化,这种慢电位变化出现在延缓期,其幅度随动物行为正确率的提高而增大,这种慢电位在前额区具有最大幅度,在中央沟以后的区域则未能记录到,负慢电位在左右两侧半球的分布基本对称,其幅度大小亦无显著差别,在延缓分辨行为反应消退后,负慢电位也随之消失,在延缓分辨作业的两种测试模式,即给予电南的R模式及不给予电击的B模式上,负慢电位均出现在延缓期,在时程和幅度上未表现出模式特异性。以上结果提示,本实验中记录到的负慢电位是依赖于学习过程的,它反映了事件间条件性联系的建立,这一负慢电位在前额皮层具有最大的幅值,并出现在延缓期的实验结果支持了前额皮层在短时记忆过程中起着重要作用的论点。     

GABA能抑制调制大棕蝠下丘听神经元时间编码模式

大棕幅（Eptesicus fuscus）下丘神经元对重复率为10pps(pulse per second）、30pps的串声刺激均产生跟随反应,但对90pps串声刺激的跟随反应则不尽相同,微电泳bicuculline阻断GABA能抑制作用后,所记录的58个神经元中,有13个（22％）放电率及串声刺激反应模式无;45个（78％）神经元放电率有不同程度的增加。对10pps、30pps串声刺激仍能产生跟随反应,但对90pps串声刺激的跟随反应模式有多种变化。其中：17个（29％）神经元为放电率增加的跟随反应;9个（15％）神经元放电率增加,对前100ms的串刺激产生反应且放电密集,而对随后200ms的串刺激只产生少量的放电;15个（26％）神经元放电率增加,在前几十毫秒范围内有较多的放电反应,后续的反应很弱;4个（7％）神经元只对第一个声刺激产生反应,且放电率增加,随后放电急剧减少。结果提示中脑下丘神经元对听觉信息的时间编码可能具有更复杂的机理。     

视觉刺激对猴初级视皮层神经元眼球位置效应的影响

用细胞外记录的方法,研究了视觉刺激对清醒猴初级视皮层神经元眼球位置效应的影响,当猴注视电视屏幕上２５个不同位置的小光点时,屏蔽上分别给予两种不同形式的视觉刺激：注视点周围的闪光圆环和感受野内的移动光条。这两种刺激都能增强初级视皮层神经元的眼球位置相关活动,并相应地使受眼球位置调制的神经元的比例明显增加。     

去甲肾上腺素对猕猴额叶延缓辨别作业相关神经元活动的效应

为了研究去甲肾上腺素在大脑认知功能中的作用,在3只猕猴进行延缓辨别作业的同时,在额叶弓状沟上支内侧部的皮层区,记录了230个作业相关神经元的电活动。对其中159个神经元观察了微量电泳去甲肾上腺素、妥拉苏林或心得安的效应。这些神经元在作业各期的分布是:开始期11个,暗示期28个,延缓期66个,反应期54个。约2/3的神经元在作业中出现兴奋反应(放电增多),1/3为抑制反应(放电减少)。在延缓期出现抑制反应的神经元,绝大多数对去甲肾上腺素敏感。在电泳去甲肾上腺素时,神经元的自发放电减少,延缓期的抑制加深。电泳妥拉苏林或心得安则出现相反的效应,即自发放电增多,延缓期的抑制减弱或不出现抑制,并可拮抗电泳去甲肾上腺素的抑制效应。实验结果提示,在额叶弓状沟上支内侧皮层神经元的注意、短时记忆等认知功能中,可能有去甲肾上腺素参与作用,主要参与神经活动的抑制过程。     

Agrotis segetum雄蛾触角叶性信息素反应神经元对电刺激触角神经的反应

为探讨电刺激Agrotis segetum雄蛾触角神经是否可以作为MGC中神经元的识别手段,采用细胞内电生理记录方法,共记录34个对性信息素有反应的MGC神经元,并测试了其中12个神经元对性信息素刺激的反应,22个神经元对性信息素刺激和电刺激的反应。结果表明,MGC神经元对性信息素及电刺激的反应模式基本一致,为一种双相反应模式。两种刺激方式均能诱导出兴奋反应,电刺激得到的兴奋反应比由信息素刺激引起的要短;MGC神经元对两种刺激的超极化反应（抑制反应）幅度影响没有显著性差别,在电刺激实验的22个神经元上,超极化反应幅度和抑制时间都与神经元本身放电频率有一定的相关性。超极化反应是在LN参与下一定的神经回路对刺激所产生的反应而形成的。这提示两种刺激所作用的神经回路应是一致的,但从整个实验过程记录到的神经元情况来看,还须进一步结合形态学实验来验证电刺激触角神经作为MGC神经元的识别手段。     

清醒猕猴前额叶和运动前区神经元多感觉活动的观察

本实验对清醒猕猴前额叶和运动前区神经元多感觉活动进行了观察。在动物进行课题操作中记录单神经元放电。课题中包括视、痛、热三种感觉刺激。在所记录的338个课题相关神经元中,对一种感觉刺激呈现反应者156个,对两种刺激反应者94个,对三种刺激都反应者88个。为了观察不具有信号意义的感觉刺激的作用,在课题操作的间歇期给动物以痛、热、视、听、触等自然刺激。在测试的176个课题相关神经元中,仅72个神经元对自然刺激呈现反应。其中对一种感觉刺激反应者45个,对两种刺激反应者19个,三种者5个,四种者3个。多数神经元对痛(N=33),视(N=30)和热(N=29)刺激呈现反应,仅有3个神经元对声音,9个神经元对触刺激出现反应。绝大多数神经元位于弓状沟上支内侧的颗粒和无颗粒皮层内。本实验表明,痛、热、触、视、听觉等投射到额叶皮层的相同部位,不同程度地会聚到同一神经元上。有信号意义的刺激与没有信号意义的刺激相比,前者可激活更多的神经元。     

猕猴额叶神经元视辨别机能可塑性的研究

我们曾经提出,额叶神经元的反应,主要不是取决于刺激物的物理属性,而是与信号意义有密切的关系。为了验证这一看法,设计了两套作业,即视延缓辨别作业(作业Ⅰ)和视辨别反应作业(作业Ⅰ),对4只成年猕猴进行实验。两套作业都由1—4期组成,在第2期都有伪随机出现的红绿灯光信号,在第3期都要求动物密切注意随后的灯光信号变化。但是,作业Ⅰ要求动物对第2期出现的红绿灯光进行辨别,作业Ⅰ则要求对第4期的红绿灯光进行辨别。待动物学会作业,正确率达90％以上,在动物进行作业的同时引导额叶神经元放电。共记录作业相关神经元163个。其中作业Ⅰ98个,作业Ⅱ 65个。在作业Ⅰ中,神经元的反应多数出现在第2、3期,占该作业反应总数的70％。而在作业Ⅱ中,反应多数出现在第3、4期,也占该作业反应总数的70％。其次,作业Ⅰ第2期的神经元反应绝大多数对红、绿灯光有明显的特异性,而作业Ⅱ第2期的则没有,只有第4期的反应才有明显的特异性。本实验结果进一步支持了我们的上述看法,并且表明,额叶神经元对信号的反应主要是在学习中逐渐形成的,有很大的可塑性。     

Social Suppressive Behavior Is Organized by the Spatiotemporal Integration of Multiple Cortical Regions in the Japanese Macaque

Under social conflict, monkeys develop hierarchical positions through social interactions. Once the hierarchy is established, the dominant monkey dominates the space around itself and the submissive monkey tries not to violate this space. Previous studies have shown the contributions of the frontal and parietal cortices in social suppression, but the contributions of other cortical areas to suppressive functions remain elusive. We recorded neural activity in large cortical areas using electrocorticographic (ECoG) arrays while monkeys performed a social food-grab task in which a target monkey was paired with either a dominant or a submissive monkey. If the paired monkey was dominant, the target monkey avoided taking food in the shared conflict space, but not in other areas. By contrast, when the paired monkey was submissive, the target monkey took the food freely without hesitation. We applied decoding analysis to the ECoG data to see when and which cortical areas contribute to social behavioral suppression. Neural information discriminating the social condition was more evident when the conflict space was set in the area contralateral to the recording hemisphere. We found that the information increased as the social pressure increased during the task. Before food presentation, when the pressure was relatively low, the parietal and somatosensory–motor cortices showed sustained discrimination of the social condition. After food presentation, when the monkey faced greater pressure to make a decision as to whether it should take the food, the prefrontal and visual cortices started to develop buildup responses. The social representation was found in a sustained form in the parietal and somatosensory–motor regions, followed by additional buildup form in the visual and prefrontal cortices. The representation was less influenced by reward expectation. These findings suggest that social adaptation is achieved by a higher-order self-regulation process (incorporating motor preparation/execution processes) in accordance with the embodied social contexts.     

Practicing coarse orientation discrimination improves orientation signals in macaque cortical area v4

Practice improves the performance in visual tasks, but mechanisms underlying this adult brain plasticity are unclear. Single-cell studies reported no [1], weak [2], or moderate [3, 4] perceptual learning-related changes in macaque visual areas V1 and V4, whereas none were found in middle temporal (MT) [5]. These conflicting results and modeling of human (e.g., [6, 7]) and monkey data [8] suggested that changes in the readout of visual cortical signals underlie perceptual learning, rather than changes in these signals. In the V4 learning studies, monkeys discriminated small differences in orientation, whereas in the MT study, the animals discriminated opponent motion directions. Analogous to the latter study, we trained monkeys to discriminate static orthogonal orientations masked by noise. V4 neurons showed robust increases in their capacity to discriminate the trained orientations during the course of the training. This effect was observed during discrimination and passive fixation but specifically for the trained orientations. The improvement in neural discrimination was due to decreased response variability and an increase of the difference between the mean responses for the two trained orientations. These findings demonstrate that perceptual learning in a coarse discrimination task indeed can change the response properties of a cortical sensory area.     

Interhemispheric functional differences in prefrontal cortex of monkeys

Monkeys had nonpolarizable electrodes implanted bilaterally in prefrontal (principal sulcus), precentral, and occipital cortex. They were trained on a spatial delayed-response (DR) task (8-sec intratrial delay), while cortical potentials were recorded. Three groups of monkeys were trained to 90% criterion: (A) 4 monkeys with only the right hand (the left wrist was attached to the testing chair); (B) 2 monkeys with only the left hand; and (C) 2 monkeys with the left and right hands on alternate sessions. Intermanual transfer tests were then given. Averaged steady potential (SP) shifts of several seconds duration were found in prefrontal cortex during cue presentation and the early portion of the intratrial delay and from the precentral area during the choice response. Evaluations of these SP shift magnitudes indicated: (1) Training with only one hand resulted in substantially larger SP shifts in the prefrontal and precentral areas contralateral to the responding hand; (2) alternate hand training resulted in somewhat larger prefrontal SP shifts in the right hemisphere; (3) intermanual transfer had marked effects on the precentral SP shifts, with larger magnitudes in the hemisphere contralateral to the responding hand, but had little effect on the magnitudes of both prefrontal SP shifts. (4) Subsequent training of Group C monkeys with only one hand resulted in greater SP shifts in the prefrontal area contralateral to the responding hand and in decreased SP shifts in the ipsilateral prefrontal area; and (5) additional intermanual transfer tests had no effects on SP shift magnitudes from both prefrontal areas. These findings indicate a dissociation in interhemispheric functions between the precentral and prefrontal cortical areas, with the former implicated in motor organization for the contralateral limb, and the latter in mediation of mnemonic processes, primarily in one hemisphere. This hemispheric specialization is affected by the hand-training procedure, but other endogenous or experiential factors may be involved.     

Fine discrimination training alters the causal contribution of macaque area MT to depth perception

When a new perceptual task is learned, plasticity occurs in the brain to mediate improvements in performance with training. How do these changes affect the neural substrates of previously learned tasks? We addressed this question by examining the effect of fine discrimination training on the causal contribution of area MT to coarse depth discrimination. When monkeys are trained to discriminate between two coarse absolute disparities (near versus far) embedded in noise, reversible inactivation of area MT devastates performance. In contrast, after animals are trained to discriminate fine differences in relative disparity, MT inactivation no longer impairs coarse depth discrimination. This effect does not result from changes in the disparity tuning of MT neurons, suggesting plasticity in the flow of disparity signals to decision circuitry. These findings show that the contribution of particular brain area to task performance can change dramatically as a result of learning new tasks.     

Prefrontal neurons predict choices during an auditory same-different task

The detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6-8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. As a test of this hypothesis, monkeys participated in a same-different task, a variant of an oddball task [2]. During this task, a monkey heard multiple presentations of a "reference" stimulus that were followed by a "test" stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of nonspatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys' choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a nonspatial auditory task.     

Odor-sampling time of mice under different conditions

Response accuracy and odor sample times on positive (S+) and negative (S-) trials were recorded for mice trained on a variety of go, no-go odor detection and discrimination tasks. Odor sample time was relatively stable over extended training on the same task, increased during acquisition of difficult tasks, relatively insensitive to reinforcement magnitude, and, in some cases, provided more information regarding task difficulty and discrimination than did response accuracy. Mice generally sampled longer on S- trials in simple odor detection tasks but longer on S+ trials in odor discrimination tasks.