Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305.
J Neurosci. 2014 Jan 8;34(2):675-87. doi: 10.1523/JNEUROSCI.1477-13.2014.
Recurrent connections in the corticothalamic circuit underlie oscillatory behavior in this network and range from normal sleep rhythms to the abnormal spike-wave discharges seen in absence epilepsy. The propensity of thalamic neurons to fire postinhibitory rebound bursts mediated by low-threshold calcium spikes renders the circuit vulnerable to both increased excitation and increased inhibition, such as excessive excitatory cortical drive to thalamic reticular (RT) neurons or heightened inhibition of thalamocortical relay (TC) neurons by RT. In this context, a protective role may be played by group III metabotropic receptors (mGluRs), which are uniquely located in the presynaptic active zone and typically act as autoreceptors or heteroceptors to depress synaptic release. Here, we report that these receptors regulate short-term plasticity at two loci in the corticothalamic circuit in rats: glutamatergic cortical synapses onto RT neurons and GABAergic synapses onto TC neurons in somatosensory ventrobasal thalamus. The net effect of group III mGluR activation at these synapses is to suppress thalamic oscillations as assayed in vitro. These findings suggest a functional role of these receptors to modulate corticothalamic transmission and protect against prolonged activity in the network.
皮质丘脑回路中的反复连接是该网络中振荡行为的基础，其范围从正常睡眠节律到癫痫失神发作中的异常棘波放电。丘脑神经元在后抑制性反弹爆发中易产生的低阈值钙峰，使得该回路容易受到兴奋和抑制的增加的影响，例如皮质对丘脑网状核（RT）神经元的过度兴奋驱动，或 RT 对丘脑皮质中继（TC）神经元的抑制增强。在这种情况下，III 组代谢型谷氨酸受体（mGluR）可能发挥保护作用，这些受体独特地位于突触前活性区，通常作为自身受体或异源受体起作用，以抑制突触释放。在这里，我们报告这些受体在大鼠皮质丘脑回路的两个部位调节短期可塑性：谷氨酸能皮质突触到 RT 神经元和 GABA 能突触到体感 Vb 丘脑的 TC 神经元。这些突触中 III 组 mGluR 的激活的净效应是抑制体外测定的丘脑振荡。这些发现表明这些受体在调节皮质丘脑传递和防止网络中长时间活动方面具有功能作用。
