Department of Molecular & Integrative Physiology, University of Illinois, Urbana-Champaign, Urbana, Illinois 61801, USA.
Synapse. 2011 Dec;65(12):1298-308. doi: 10.1002/syn.20964. Epub 2011 Aug 12.
The thalamus serves as the obligatory gateway to the neocortex for sensory processing, and also serves as a pathway for corticocortical communication. In addition, the reciprocal synaptic connectivity between the thalamic reticular nucleus (TRN) and adjacent thalamic relay nuclei generates rhythmic activities similar to that observed during different arousal states and certain neurological conditions such as absence epilepsy. Epileptiform activity can arise from a variety of neural mechanisms, but in addition glia are thought to have an important role in such activities as well. Glia serve a central role in glutamine synthesis, a precursor for glutamate or GABA in nerve terminals. While alterations in glutamine shuttling from glia to neurons can influence GABA and glutamate neurotransmission; the consequences of such action on synaptic transmission and subsequent network activities within thalamic circuits is less understood. We investigated the consequences of altering glutamine transport on inhibitory transmission and intrathalamic activities using the in vitro thalamic slice preparation. Disruption of the glutamine shuttling by the neuronal glutamine transporter (system A transporter) antagonist, α-(methylamino)isobutyric acid (MeAIB), or the selective gliotoxic drug, fluorocitric acid (Fc) dramatically decreased intrathalamic rhythmic activities. At the single cell level, MeAIB and Fc significantly attenuated electrically evoked inhibitory postsynaptic currents (eIPSCs) in thalamic relay neurons; however, miniature IPSCs were unaffected. These data indicate that glutamate-glutamine shuttle is critical for sustaining thalamic synaptic transmission, and thereby alterations in this shuttle can influence intrathalamic rhythmic activities associated with absence epilepsy.
丘脑是感觉处理向新皮层传递的必经之门户，也是皮质间通讯的途径。此外，丘脑网状核（TRN）与相邻的丘脑中继核之间的相互突触连接产生类似于不同觉醒状态和某些神经状况（如失神癫痫）下观察到的节律性活动。癫痫样活动可由多种神经机制引起，但胶质细胞也被认为在这些活动中起重要作用。胶质细胞在谷氨酰胺合成中起核心作用，谷氨酰胺是神经末梢谷氨酸或 GABA 的前体。虽然来自胶质细胞向神经元的谷氨酰胺转运的改变会影响 GABA 和谷氨酸神经传递；但这种作用对突触传递和随后的网络活动的影响在丘脑回路中理解较少。我们使用体外丘脑切片制备来研究改变谷氨酰胺转运对抑制性传递和丘脑内活动的影响。神经元谷氨酰胺转运体（系统 A 转运体）拮抗剂 α-（甲基氨基）异丁酸（MeAIB）或选择性神经毒性药物氟柠檬酸（Fc）对谷氨酰胺转运的破坏显著降低了丘脑内的节律性活动。在单细胞水平上，MeAIB 和 Fc 显著减弱了电诱发的抑制性突触后电流（eIPSCs）在丘脑中继神经元中的传递；然而，微小 IPSCs 不受影响。这些数据表明，谷氨酸-谷氨酰胺穿梭对维持丘脑突触传递至关重要，因此穿梭的改变会影响与失神癫痫相关的丘脑内节律性活动。
