Institut National de la Santé et de la Recherche Médicale, U 836, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, France.
PLoS One. 2012;7(7):e41793. doi: 10.1371/journal.pone.0041793. Epub 2012 Jul 27.
The substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia, delivering inhibitory efferents to the relay nuclei of the thalamus. Pathological hyperactivity of SNr neurons is known to be responsible for some motor disorders e.g. in Parkinson's disease. One way to restore this pathological activity is to electrically stimulate one of the SNr input, the excitatory subthalamic nucleus (STN), which has emerged as an effective treatment for parkinsonian patients. The neuronal network and signal processing of the basal ganglia are well known but, paradoxically, the role of astrocytes in the regulation of SNr activity has never been studied.
In this work, we developed a rat brain slice model to study the influence of spontaneous and induced excitability of afferent nuclei on SNr astrocytes calcium activity. Astrocytes represent the main cellular population in the SNr and display spontaneous calcium activities in basal conditions. Half of this activity is autonomous (i.e. independent of synaptic activity) while the other half is dependent on spontaneous glutamate and GABA release, probably controlled by the pace-maker activity of the pallido-nigral and subthalamo-nigral loops. Modification of the activity of the loops by STN electrical stimulation disrupted this astrocytic calcium excitability through an increase of glutamate and GABA releases. Astrocytic AMPA, mGlu and GABA(A) receptors were involved in this effect.
Astrocytes are now viewed as active components of neural networks but their role depends on the brain structure concerned. In the SNr, evoked activity prevails and autonomous calcium activity is lower than in the cortex or hippocampus. Our data therefore reflect a specific role of SNr astrocytes in sensing the STN-GPe-SNr loops activity and suggest that SNr astrocytes could potentially feedback on SNr neuronal activity. These findings have major implications given the position of SNr in the basal ganglia network.
黑质网状部（SNr）是基底神经节的主要输出核团，向丘脑中继核团发出抑制性传出。已知 SNr 神经元的病理性过度活动是导致某些运动障碍的原因，例如帕金森病。恢复这种病理性活动的一种方法是电刺激 SNr 的一个输入，兴奋性的丘脑下核（STN），这已成为帕金森病患者的有效治疗方法。基底神经节的神经网络和信号处理是众所周知的，但矛盾的是，星形胶质细胞在调节 SNr 活性中的作用从未被研究过。
在这项工作中，我们开发了一种大鼠脑片模型，以研究传入核自发和诱导兴奋性对 SNr 星形胶质细胞钙活性的影响。星形胶质细胞是 SNr 中的主要细胞群体，在基础条件下显示出自发的钙活性。这种活性的一半是自主的（即独立于突触活动），而另一半依赖于自发的谷氨酸和 GABA 释放，可能由苍白球-黑质和丘脑下核-黑质环的起搏器活动控制。通过 STN 电刺激改变这些环路的活动，通过增加谷氨酸和 GABA 的释放，破坏了这种星形胶质细胞钙兴奋性。星形胶质细胞的 AMPA、mGlu 和 GABA(A)受体参与了这种效应。
星形胶质细胞现在被视为神经网络的活跃成分，但它们的作用取决于所涉及的大脑结构。在 SNr 中，诱发活动占主导地位，自主钙活性低于皮层或海马体。因此，我们的数据反映了 SNr 星形胶质细胞在感知 STN-GPe-SNr 环路活动中的特定作用，并表明 SNr 星形胶质细胞可能潜在地反馈 SNr 神经元活动。鉴于 SNr 在基底神经节网络中的位置，这些发现具有重要意义。
