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。     

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     

猕猴执行痛,热延缓辨别作业时额叶神经元及肌电...

To study the functional implication of neuronal responses in frontal cortex to noxious and innocuous heat stimuli, experiments were carried out on two monkeys (Macaca mulatta) during performing a delayed discrimination GO/NO-GO task. The animals were trained to hold a lever for at least 3 s in the response period when an innocuous heat stimulus had been applied to the forearm in the cue period, or release it within 1 s with a noxious one. After a criterion of 90% of correct responses in 3 successive days was reached, single neuronal activity was recorded from the frontal cortex along with EMGs from six muscles in both arms. Of 142 task-related neurons recorded, 87 (66.4%) were related to heat, 34 to visual, and 21 to both visual and heat stimuli. Among the heat-related neurons, 22 were responsive to noxious heat, 18 to innocuous heat, and 47 to both. Of the neurons responding to both noxious and innocuous heat stimuli, 4 neurons showed changes in discharge rates, depending on the type of stimuli. In most cases, muscular activities just appeared at the moment of lever pressing and/or releasing in m. extensor digitorium communis, m. flexor carpi ulnaris and m. flexor carpi radialis of the performing arm. No regular muscular activities appeared in other muscles and in other periods of the task. The result showed that the neuronal responses in frontal cortex elicited by heat stimuli in the cue period were not related directly to the initiation and modulation of behaviours.(ABSTRACT TRUNCATED AT 250 WORDS)     

A cortical substrate for memory-guided orienting in the rat

Anatomical, stimulation, and lesion data have suggested a homology between the rat frontal orienting fields (FOF) (centered at?+2 AP,?±1.3 ML mm from Bregma) and primate frontal cortices such as the frontal or supplementary eye fields. We investigated the functional role of the FOF using rats trained to perform a memory-guided orienting task, in which there was a delay period between the end of?a sensory stimulus instructing orienting direction and the time of the allowed motor response. Unilateral inactivation of the FOF resulted in impaired contralateral responses. Extracellular recordings of single units revealed that 37% of FOF neurons had delay period firing rates that predicted the direction of the rats' later orienting motion. Our data provide the first electrophysiological and pharmacological evidence supporting the existence in the rat, as in the primate, of a frontal cortical area involved in the preparation and/or planning of orienting responses.     

Single neurons in posterior parietal cortex of monkeys encode cognitive set

The primate posterior parietal cortex (PPC), part of the dorsal visual pathway, is best known for its role in encoding salient spatial information. Yet there are indications that neural activity in the PPC can also be modulated by nonspatial task-related information. In this study, we tested whether neurons in the PPC encode signals related to cognitive set, that is, the preparation to perform a particular task. Cognitive set has previously been associated with the frontal cortex but not the PPC. In this study, monkeys performed a cognitive set shifting paradigm in which they were cued in advance to apply one of two different task rules to the subsequent stimulus on every trial. Here we show that a subset of neurons in the PPC, concentrated in the lateral bank of the intraparietal sulcus and on the angular gyrus, responds selectively to cues for different task rules.     

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。     

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     

Electrophysiological actions of VIP in rat somatosensory cortex.

Electrophysiological and biochemical studies suggest that VIP may exert a facilitating action in the neocortical local circuitry. In the present study, we examined the actions of VIP and VIP + norepinephrine (NE) on somatosensory cortical neuron responses to direct application of the putative transmitters acetylcholine (ACh) and gamma-aminobutyric acid (GABA). Spontaneous and transmitter-induced discharges of cortical neurons from halothane-anesthetized rats were monitored before, during and after VIP, NE and VIP + NE iontophoresis. In 57 VIP-sensitive cells tested, VIP application (5-70 nA) increased (n = 18), decreased (n = 36) or had biphasic actions (n = 3) on background firing rate. In a group of 20 neurons tested for NE + VIP, the combined effect of both peptide and bioamine was predominantly (70%) inhibitory. On the other hand, inhibitory and excitatory responses of cortical neurons to GABA (11 of 15 cases) and ACh (10 of 18 cases), respectively, were enhanced during VIP iontophoresis. Concomitant application of VIP and NE produced additive (n = 2) or more than additive (n = 3) enhancing effects on GABA inhibition. NE administration reversed or enhanced further VIP modulatory actions on ACh-induced excitation. These findings provide electrophysiological evidence that NE and VIP afferents may exert convergent influences on cortical neuronal responses to afferent synaptic inputs such that modulatory actions are anatomically focused within the cortex.     

Stress-Induced Impairment of a Working Memory Task: Role of Spiking Rate and Spiking History Predicted Discharge

Stress, pervasive in society, contributes to over half of all work place accidents a year and over time can contribute to a variety of psychiatric disorders including depression, schizophrenia, and post-traumatic stress disorder. Stress impairs higher cognitive processes, dependent on the prefrontal cortex (PFC) and that involve maintenance and integration of information over extended periods, including working memory and attention. Substantial evidence has demonstrated a relationship between patterns of PFC neuron spiking activity (action-potential discharge) and components of delayed-response tasks used to probe PFC-dependent cognitive function in rats and monkeys. During delay periods of these tasks, persistent spiking activity is posited to be essential for the maintenance of information for working memory and attention. However, the degree to which stress-induced impairment in PFC-dependent cognition involves changes in task-related spiking rates or the ability for PFC neurons to retain information over time remains unknown. In the current study, spiking activity was recorded from the medial PFC of rats performing a delayed-response task of working memory during acute noise stress (93 db). Spike history-predicted discharge (SHPD) for PFC neurons was quantified as a measure of the degree to which ongoing neuronal discharge can be predicted by past spiking activity and reflects the degree to which past information is retained by these neurons over time. We found that PFC neuron discharge is predicted by their past spiking patterns for nearly one second. Acute stress impaired SHPD, selectively during delay intervals of the task, and simultaneously impaired task performance. Despite the reduction in delay-related SHPD, stress increased delay-related spiking rates. These findings suggest that neural codes utilizing SHPD within PFC networks likely reflects an additional important neurophysiological mechanism for maintenance of past information over time. Stress-related impairment of this mechanism is posited to contribute to the cognition-impairing actions of stress.     

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。