Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Mol Pain. 2010 Sep 13;6:52. doi: 10.1186/1744-8069-6-52.
Gastrin-releasing peptide (GRP) has been proposed as a peptidergic molecule for behavioral fear and itching. Immunohistochemistry and in situ hybridization studies have shown that GRP and GRP receptor are widely distributed in forebrain areas. Less information is available for the functional action for GRP in the prefrontal cortex including the anterior cingulate cortex (ACC). Here we used whole-cell patch-clamp recording technique to study the modulation of synaptic transmission by GRP in the ACC. We found that GRP increased the frequency of sIPSCs recorded while had no significant effect on sEPSCs in ACC pyramidal neurons. The facilitatory effect of GRP on sIPSCs was blocked by the GRP receptor antagonist, RC3095. In the presence of TTX, however, GRP had no effect on the mIPSCs. Therefore, activation of GRP receptor may facilitate the excitation of the interneurons and enhanced spontaneous GABAergic, but not glutamatergic neurotransmission. Similar results on GRP modulation of GABAergic transmission were observed in the insular cortex and amygdala, suggesting a general possible effect of GRP on cortical inhibitory transmission. Our results suggest that GRP receptor is an important regulator of inhibitory circuits in forebrain areas.
胃泌素释放肽(GRP)被提出作为行为性恐惧和瘙痒的肽类分子。免疫组织化学和原位杂交研究表明,GRP 和 GRP 受体广泛分布在前脑区域。对于 GRP 在包括前扣带皮层(ACC)在内的前额叶皮层中的功能作用,信息较少。在这里,我们使用全细胞膜片钳记录技术研究了 GRP 对 ACC 中突触传递的调制。我们发现 GRP 增加了记录的 sIPSCs 的频率,而对 ACC 锥体神经元中的 sEPSCs 没有显著影响。GRP 对 sIPSCs 的促进作用被 GRP 受体拮抗剂 RC3095 阻断。然而,在 TTX 存在的情况下,GRP 对 mIPSCs 没有影响。因此,GRP 受体的激活可能促进中间神经元的兴奋,并增强自发性 GABA 能但不是谷氨酸能神经传递。在岛叶皮层和杏仁核中也观察到 GRP 对 GABA 能传递的类似调制作用,表明 GRP 对皮质抑制性传递可能具有普遍的作用。我们的结果表明,GRP 受体是前脑区域抑制性回路的重要调节剂。