Rammes G, Eder M, Dodt H U, Kochs E, Zieglgänsberger W
Max-Planck-Institute of Psychiatry, Munich, Germany.
Neuroscience. 2001;107(1):85-97. doi: 10.1016/s0306-4522(01)00336-0.
Long-term depression (LTD) in the basolateral amygdala, following low frequency stimulation (1 Hz/900 pulses) of the lateral amygdala, was studied in an in vitro slice preparation of 2-3 weeks and 2-4 months old mice. Whole-cell patch-clamp recordings of neurons, visualized by means of infrared videomicroscopy, and extracellular field potential recordings were performed. Loading single neurons with the calcium chelator BAPTA (30 mM) did not reduce the excitatory postsynaptic currents following low frequency stimulation. However, buffering presynaptic calcium with BAPTA-AM, and application of the specific Ca2+/calmodulin-stimulated protein kinase II antagonist KN-62 (1-[N,O-bis(5-isoquinoline sulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperizine), blocked low frequency stimulation-induced LTD. The induction of LTD was reduced by the competitive N-methyl-D-aspartate receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (50 microM), and blocked by the metabotropic glutamate receptor antagonist (-)-amino-4-carboxy-methyl-phenylacetic acid (1 mM), and by 5-hydroxytryptamine (5-HT; 30 microM) via the activation of 5-HT(1A) receptors. Also blocking GABA(A) receptor-mediated synaptic transmission with bicuculline (10 microM) or picrotoxin (20 microM) reduced the induction of LTD. Visually and electrophysiologically identified interneurons in slices from 2 weeks old mice, expressed in contrast to adult mice (2-4 months), pronounced LTD. Principal neurons showed only weak LTD after low frequency stimulation.A synopsis of these findings suggests a pivotal role of GABAergic interneurons and serotonergic afferents in the induction of LTD in the basolateral nucleus of the amygdala.
在2至3周龄和2至4月龄小鼠的体外脑片制备中，研究了杏仁核基底外侧核在低频刺激（1赫兹/900个脉冲）杏仁核外侧后出现的长时程抑制（LTD）。通过红外视频显微镜对神经元进行全细胞膜片钳记录，并进行细胞外场电位记录。用钙螯合剂BAPTA（30毫摩尔）加载单个神经元，并不会降低低频刺激后的兴奋性突触后电流。然而，用BAPTA-AM缓冲突触前钙，以及应用特异性Ca2+/钙调蛋白刺激的蛋白激酶II拮抗剂KN-62（1-[N,O-双（5-异喹啉磺酰基）-N-甲基-L-酪氨酰基]-4-苯基哌嗪），可阻断低频刺激诱导的LTD。LTD的诱导被竞争性N-甲基-D-天冬氨酸受体拮抗剂D-（-）-2-氨基-5-膦酰戊酸（50微摩尔）降低，并被代谢型谷氨酸受体拮抗剂（-）-氨基-4-羧基-甲基苯乙酸（1毫摩尔）以及5-羟色胺（5-HT；30微摩尔）通过激活5-HT（1A）受体所阻断。用荷包牡丹碱（10微摩尔）或印防己毒素（20微摩尔）阻断GABA（A）受体介导的突触传递，也会降低LTD的诱导。与成年小鼠（2至4个月）相比，2周龄小鼠脑片中通过视觉和电生理鉴定的中间神经元表现出明显的LTD。主要神经元在低频刺激后仅表现出微弱的LTD。这些发现的概要表明，GABA能中间神经元和5-羟色胺能传入神经在杏仁核基底外侧核LTD的诱导中起关键作用。
