Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-746, Korea.
J Neurosci. 2012 Aug 15;32(33):11318-29. doi: 10.1523/JNEUROSCI.0146-12.2012.
Long-term depression (LTD) is a key form of synaptic plasticity important in learning and information storage in the brain. It has been studied in various cortical regions, including the anterior cingulate cortex (ACC). ACC is a crucial cortical region involved in such emotion-related physiological and pathological conditions as fear memory and chronic pain. In the present study, we used a multielectrode array system to map cingulate LTD in a spatiotemporal manner within the ACC. We found that low-frequency stimulation (1 Hz, 15 min) applied onto deep layer V induced LTD in layers II/III and layers V/VI. Cingulate LTD requires activation of metabotropic glutamate receptors (mGluRs), while L-type voltage-gated calcium channels and NMDA receptors also contribute to its induction. Peripheral amputation of the distal tail impaired ACC LTD, an effect that persisted for at least 2 weeks. The loss of LTD was rescued by priming ACC slices with activation of mGluR1 receptors by coapplying (RS)-3,5-dihydroxyphenylglycine and MPEP, a form of metaplasticity that involved the activation of protein kinase C. Our results provide in vitro evidence of the spatiotemporal properties of ACC LTD in adult mice. We demonstrate that tail amputation causes LTD impairment within the ACC circuit and that this can be rescued by activation of mGluR1.
长时程抑制(LTD)是大脑中学习和信息存储的重要突触可塑性形式。它已在包括前扣带皮层(ACC)在内的各种皮质区域中进行了研究。ACC 是涉及恐惧记忆和慢性疼痛等与情绪相关的生理和病理状况的关键皮质区域。在本研究中,我们使用多电极阵列系统以时空方式在 ACC 内映射扣带 LTD。我们发现,施加于深层 V 的低频刺激(1 Hz,15 分钟)在 II/III 层和 V/VI 层中诱导 LTD。扣带 LTD 需要代谢型谷氨酸受体(mGluRs)的激活,而 L 型电压门控钙通道和 NMDA 受体也有助于其诱导。尾部末梢截断会损害 ACC LTD,这种效应至少持续 2 周。用(RS)-3,5-二羟苯甘氨酸和 MPEP (一种涉及蛋白激酶 C 激活的形式)共同应用来激活 mGluR1 受体,可使 ACC 切片预激活,从而挽救 LTD 的丧失。我们的结果提供了成年小鼠 ACC LTD 的时空特性的体外证据。我们证明尾部截断会导致 ACC 回路中的 LTD 损伤,而通过激活 mGluR1 可以挽救这种损伤。