Fong Ming-fai, Newman Jonathan P, Potter Steve M, Wenner Peter
1] Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA [2] Laboratory for Neuroengineering, Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA [3] Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
1] Laboratory for Neuroengineering, Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA [2] Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nat Commun. 2015 Mar 9;6:6339. doi: 10.1038/ncomms7339.
Homeostatic plasticity encompasses a set of mechanisms that are thought to stabilize firing rates in neural circuits. The most widely studied form of homeostatic plasticity is upward synaptic scaling (upscaling), characterized by a multiplicative increase in the strength of excitatory synaptic inputs to a neuron as a compensatory response to chronic reductions in firing rate. While reduced spiking is thought to trigger upscaling, an alternative possibility is that reduced glutamatergic transmission generates this plasticity directly. However, spiking and neurotransmission are tightly coupled, so it has been difficult to determine their independent roles in the scaling process. Here we combined chronic multielectrode recording, closed-loop optogenetic stimulation, and pharmacology to show that reduced glutamatergic transmission directly triggers cell-wide synaptic upscaling. This work highlights the importance of synaptic activity in initiating signalling cascades that mediate upscaling. Moreover, our findings challenge the prevailing view that upscaling functions to homeostatically stabilize firing rates.
稳态可塑性包含一系列被认为可稳定神经回路放电率的机制。稳态可塑性研究最为广泛的形式是突触向上缩放（增强），其特征是神经元兴奋性突触输入强度呈倍增增加，作为对放电率长期降低的一种补偿反应。虽然认为放电减少会触发向上缩放，但另一种可能性是谷氨酸能传递减少直接产生这种可塑性。然而，放电和神经传递紧密耦合，因此很难确定它们在缩放过程中的独立作用。在这里，我们结合慢性多电极记录、闭环光遗传学刺激和药理学方法，证明谷氨酸能传递减少直接触发全细胞突触向上缩放。这项工作突出了突触活动在启动介导向上缩放的信号级联反应中的重要性。此外，我们的研究结果挑战了普遍观点，即向上缩放的功能是通过稳态来稳定放电率。
