Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
Neuroscience. 2009 Dec 29;164(4):1389-97. doi: 10.1016/j.neuroscience.2009.09.061. Epub 2009 Sep 25.
Previous behavioral studies have shown that neuropeptides intrinsic to the amygdala formation can alter fear and anxiety states. We have previously shown that the anxiogenic neuropeptide cholecystokinin (CCK) increases inhibitory neurotransmission in basolateral amygdala. We have since observed that CCK induces synchronized rhythmic activity composed of compound postsynaptic potentials (cPSPs). We have now further characterized these cPSPs by inducing cPSPs routinely in 5 mM extracellular K(+). CCK facilitated cPSP occurrence in a dose dependent manner in brain slices from both young and mature rats. The cPSPs were attenuated by glutamate receptor antagonists (NBQX or DL-AP5) or low concentrations of GABA(A) receptor antagonists (bicuculline methiodide (BMI), SR95531, or picrotoxin), but not by the GABA(B) receptor antagonist, CGP52432. Low concentrations of tetrodotoxin (TTX, 10 nM) also attenuated the cPSPs. The Na-K-2Cl cotransporter blocker, bumetanide (1 or 10 microM) also blocked the cPSPs. The anxiogenic neuropeptide corticotropin-releasing factor (CRF) facilitated cPSPs while anxiolytic neuropeptides (neuropeptide Y (NPY) and somatostatin) attenuated cPSPs. The benzodiazepine agonist diazepam dose-dependently modulated cPSPs. Mefloquine facilitated cPSPs within 10 min of application. We hypothesize that cPSPs are generated by positive feedback between a subset of interneurons and a subset of glutamatergic projection neurons.
先前的行为研究表明，杏仁核形成中的内源性神经肽可以改变恐惧和焦虑状态。我们之前已经表明，焦虑神经肽胆囊收缩素（CCK）增加了基底外侧杏仁核中的抑制性神经传递。此后，我们观察到 CCK 诱导由复合突触后电位（cPSP）组成的同步节律性活动。我们现在通过在 5mM 细胞外 K+中常规诱导 cPSP 进一步对这些 cPSP 进行了特征描述。CCK 以剂量依赖的方式促进年轻和成熟大鼠脑片中 cPSP 的发生。谷氨酸受体拮抗剂（NBQX 或 DL-AP5）或低浓度 GABA(A)受体拮抗剂（荷包牡丹碱甲碘化物（BMI）、SR95531 或荷包牡丹碱）可减弱 cPSP，但 GABA(B)受体拮抗剂 CGP52432 则不能。低浓度的河豚毒素（TTX，10 nM）也减弱了 cPSP。Na-K-2Cl 共转运体阻滞剂布美他尼（1 或 10 μM）也阻断了 cPSP。焦虑神经肽促肾上腺皮质激素释放因子（CRF）促进 cPSP，而焦虑神经肽（神经肽 Y（NPY）和生长抑素）则减弱了 cPSP。苯二氮䓬类激动剂地西泮剂量依赖性地调节 cPSP。甲氟喹在应用后 10 分钟内促进 cPSP。我们假设 cPSP 是由一组中间神经元和一组谷氨酸能投射神经元之间的正反馈产生的。
