Presynaptic inhibition of corticothalamic feedback by metabotropic glutamate receptors
Presynaptic inhibition of corticothalamic feedback by metabotropic glutamate receptors
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DOI：
10.1152/jn.01198.2004
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发表时间：
2005-07-01
影响因子：
2.5
通讯作者：
Godwin, DW
中科院分区：
文献类型：
--
作者：
Alexander, GM;Godwin, DW
丘脑将感觉信息传递到大脑皮质，但这一信息可能受到来自皮质VI层的兴奋性反馈的影响。这种反馈的全部重要性直到最近才被探索，但其可能的功能包括对感觉特征的处理、丘脑放电的同步性以及丘脑中继细胞反应模式的转换。不受控制的皮质丘脑反馈也与某些神经疾病相关的病理性丘脑节律有关。我们发现了一种突触前抑制皮质丘脑突触传递的形式，这种抑制是由第二组代谢性谷氨酸受体(MGluR)介导的，并由高频皮质丘脑活动激活。我们测试了雪貂丘脑外侧膝状体背侧核中推测的视黄醇生成和皮质生成突触对第二组mGluR的调节。刺激视束纤维引起兴奋性突触后电流(EPSCs)的双脉冲抑制，而刺激视神经辐射则引起双脉冲易化。随后使用成对脉冲反应来表征受刺激突触的起源路径。Ⅱ组mGluR激动剂(LY379268和DCG-IV)在电压钳条件下作用于丘脑神经元，可降低皮质源性EPSCs的幅度。高频串刺激产生的易化反应被第二组mGluR激动剂减弱，但被选择性拮抗剂LY341495增强，揭示了突触前mGluR介导的高频皮质激素反馈的减少。激动剂治疗不影响刺激视束的EPSCs。NAAG(据报道对mGluR3具有选择性)对皮质膝状体突触无效，暗示mGluR2参与了观察到的效应。我们的数据首次显示了一种突触诱导的突触前抑制形式的皮质-丘脑突触传递，这种抑制是由mGluR2的突触前作用介导的。这种突触前抑制可能部分地静音感觉反馈，并防止重入兴奋引发异常的丘脑节律。
The thalamus relays sensory information to cortex, but this information may be influenced by excitatory feedback from cortical layer VI. The full importance of this feedback has only recently been explored, but among its possible functions are influences on the processing of sensory features, synchronization of thalamic firing, and transitions in response mode of thalamic relay cells. Uncontrolled, corticothalamic feedback has also been implicated in pathological thalamic rhythms associated with certain neurological disorders. We have found a form of presynaptic inhibition of corticothalamic synaptic transmission that is mediated by a Group II metabotropic glutamate receptor (mGluR) and activated by high-frequency corticothalamic activity. We tested putative retinogeniculate and corticogeniculate synapses for Group II mGluR modulation within the dorsal lateral geniculate nucleus of the ferret thalamus. Stimulation of optic-tract fibers elicited paired-pulse depression of excitatory postsynaptic currents (EPSCs), whereas stimulation of the optic radiations elicited paired-pulse facilitation. Paired-pulse responses were subsequently used to characterize the pathway of origin of stimulated synapses. Group II mGluR agonists (LY379268 and DCG-IV) applied to thalamic neurons under voltage-clamp conditions reduced the amplitude of corticogeniculate EPSCs. Stimulation with high-frequency trains produced a facilitating response that was reduced by Group II mGluR agonists, but was enhanced by the selective antagonist LY341495, revealing a presynaptic, mGluR-mediated reduction of high-frequency corticogeniculate feedback. Agonist treatment did not affect EPSCs from stimulation of the optic tract. NAAG (reported to be selective for mGluR3) was ineffective at the corticogeniculate synapse, implicating mGluR2 in the observed effects. Our data are the first to show a synaptically elicited form of presynaptic inhibition of corticothalamic synaptic transmission that is mediated by presynaptic action of mGluR2. This presynaptic inhibition may partially mute sensory feedback and prevent reentrant excitation from initiating abnormal thalamic rhythms.