Sgambato V, Abo V, Rogard M, Besson M J, Deniau J M
Université Pierre et Marie Curie, Department de Neurochimie-Anatomie, U.R.A. 1488, Paris, France.
Neuroscience. 1997 Nov;81(1):93-112. doi: 10.1016/s0306-4522(97)00179-6.
The protein Fos is a transcription factor which is quickly induced in response to a variety of extracellular signals. Since this protein is expressed in a variety of neuronal systems in response to activation of synaptic afferents, it has been suggested that it might contribute to activity-dependent plasticity in neural networks. The present study investigated the effect of cortical electrical stimulation on the expression of Fos in the basal ganglia in the rat, a group of structures that participate in sensorimotor learning. Results show that the repetitive application of electrical shocks in restricted areas of the cerebral cortex induces an expression of Fos mostly confined to the striatum and the subthalamic nucleus. The induction which can be elicited from different cortical areas (sensorimotor, auditory and limbic areas) does not require particular temporal patterns of stimulation but rather depends on the total number of shocks delivered during a given period of time. Moreover, it appears to be rather independent of the number of spikes discharged by the activated cells. In the striatum, the distribution of immunoreactive neurons is precisely delineated and conforms to the known topographical organization of stimulated corticostriatal projections. As demonstrated using a variety of double labelling techniques (combination of the immunocytochemical detection of Fos with the autoradiography of mu opioid receptors, calbindin immunocytochemistry, in situ hybridization of preproenkephalin and preprotachykinin A messenger RNAs), striatal neurons which express Fos are mostly localized in the matrix compartment and concern equally enkephaline and substance P containing efferent neurons. In the subthalamic nucleus, Fos expression evoked by cortical stimulation is also confined to discrete regions of the nucleus, the localizations corresponding to the primary projection site of the stimulated cortical cells. These results indicate that in addition to its phasic synaptic influence on the basal ganglia, the cerebral cortex could exert a long-term effect on the functional state of this system via a genomic control. Since the basal ganglia are involved in sensorimotor learning and motor habit formation, it is tempting to speculate that the activity-dependent Fos induction at corticostriatal and subthalamic synapses may contribute to consolidate the functionality of the neuronal networks activated during the completion of given motor tasks.
蛋白质Fos是一种转录因子,可快速响应多种细胞外信号而被诱导产生。由于这种蛋白质在多种神经元系统中表达,以响应突触传入神经的激活,因此有人提出它可能有助于神经网络中依赖活动的可塑性。本研究调查了皮质电刺激对大鼠基底神经节中Fos表达的影响,基底神经节是一组参与感觉运动学习的结构。结果表明,在大脑皮质的受限区域重复施加电击会诱导Fos的表达,其主要局限于纹状体和丘脑底核。从不同皮质区域(感觉运动区、听觉区和边缘区)引发的诱导不需要特定的刺激时间模式,而是取决于给定时间段内传递的电击总数。此外,它似乎相当独立于被激活细胞放电的尖峰数量。在纹状体中,免疫反应性神经元的分布被精确描绘,并符合已知的受刺激皮质纹状体投射的拓扑组织。使用多种双重标记技术(Fos的免疫细胞化学检测与μ阿片受体的放射自显影、钙结合蛋白免疫细胞化学、前脑啡肽原和前速激肽原A信使RNA的原位杂交相结合)证明,表达Fos的纹状体神经元大多位于基质区室,并且同样涉及含脑啡肽和P物质的传出神经元。在丘脑底核中,皮质刺激引起的Fos表达也局限于该核的离散区域,其定位对应于受刺激皮质细胞的主要投射部位。这些结果表明,除了对基底神经节的相位突触影响外,大脑皮质还可以通过基因组控制对该系统的功能状态产生长期影响。由于基底神经节参与感觉运动学习和运动习惯形成,因此很容易推测,皮质纹状体和丘脑底核突触处依赖活动的Fos诱导可能有助于巩固在完成给定运动任务期间激活的神经网络的功能。