Mateo Z, Porter J T
Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, PO Box 7004, Ponce, Puerto Rico 00732.
Neuroscience. 2007 May 25;146(3):1062-72. doi: 10.1016/j.neuroscience.2007.02.053. Epub 2007 Apr 6.
Thalamocortical synapses provide a strong glutamatergic excitation to cortical neurons that is critical for processing sensory information. Unit recordings in vivo indicate that metabotropic glutamate receptors (mGluRs) reduce the effect of thalamocortical input on cortical circuits. However, it is not known whether this reduction is due to a reduction in glutamate release from thalamocortical terminals or from a decrease in cortical neuron excitability. To directly determine whether mGluRs act as autoreceptors on thalamocortical terminals, we examined the effect of mGluR agonists on thalamocortical synapses in slices. Thalamocortical excitatory postsynaptic currents (EPSCs) were recorded in layer IV cortical neurons in developing mouse brain slices. The activation of group II mGluRs with (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) reduced thalamocortical EPSCs in both excitatory and inhibitory neurons, while the stimulation of group I or group III mGluRs had no effect on thalamocortical EPSCs. Consistent with a reduction in glutamate release, DCG IV increased the paired pulse ratio and the coefficient of variation of the EPSCs. The reduction induced by DCG IV was reversed by the group II mGluR antagonist, LY341495, and mimicked by another selective group II agonist, (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid (APDC). The mGluR2 subtype appears to mediate the reduction of thalamocortical EPSCs, since the selective mGluR3 agonist, N-acetylaspartylglutamate (NAAG), had no effect on the EPSCs. Consistent with this, we showed that mGluR2 is expressed in the barrels. Furthermore, blocking group II mGluRs with LY341495 reduced the synaptic depression induced by a short stimulus train, indicating that synaptically released glutamate activates these receptors. These results indicate that group II mGluRs modulate thalamocortical processing by inhibiting glutamate release from thalamocortical synapses. This inhibition provides a feedback mechanism for preventing excessive excitation of cortical neurons that could play a role in the plasticity and refinement of thalamocortical connections during this early developmental period.
丘脑皮质突触为皮质神经元提供强大的谷氨酸能兴奋性，这对于处理感觉信息至关重要。体内单位记录表明，代谢型谷氨酸受体（mGluRs）可降低丘脑皮质输入对皮质回路的影响。然而，尚不清楚这种降低是由于丘脑皮质终末谷氨酸释放减少，还是由于皮质神经元兴奋性降低所致。为了直接确定mGluRs是否作为丘脑皮质终末的自身受体起作用，我们在脑片中研究了mGluR激动剂对丘脑皮质突触的影响。在发育中小鼠脑片的IV层皮质神经元中记录丘脑皮质兴奋性突触后电流（EPSCs）。用（2S,2'R,3'R）-2-（2',3'-二羧基环丙基）甘氨酸（DCG IV）激活II组mGluRs可降低兴奋性和抑制性神经元中的丘脑皮质EPSCs，而刺激I组或III组mGluRs对丘脑皮质EPSCs无影响。与谷氨酸释放减少一致，DCG IV增加了EPSCs的配对脉冲比率和变异系数。DCG IV诱导的降低被II组mGluR拮抗剂LY341495逆转，并被另一种选择性II组激动剂（2R,4R）-4-氨基吡咯烷-2,4-二羧酸（APDC）模拟。mGluR2亚型似乎介导了丘脑皮质EPSCs的降低，因为选择性mGluR3激动剂N-乙酰天冬氨酰谷氨酸（NAAG）对EPSCs无影响。与此一致，我们表明mGluR2在桶状区表达。此外，用LY341495阻断II组mGluRs可减少短刺激序列诱导的突触抑制，表明突触释放的谷氨酸激活了这些受体。这些结果表明，II组mGluRs通过抑制丘脑皮质突触中的谷氨酸释放来调节丘脑皮质加工。这种抑制提供了一种反馈机制，用于防止皮质神经元过度兴奋，这可能在这个早期发育阶段丘脑皮质连接的可塑性和精细化中发挥作用。
