Experimental Epilepsy Group, Wallenberg Neuroscience Center, Lund University Hospital, Sweden.
Hippocampus. 2011 Feb;21(2):198-211. doi: 10.1002/hipo.20740.
Cholecystokinin (CCK)-expressing basket cells encompass a subclass of inhibitory GABAergic interneurons that regulate memory-forming oscillatory network activity of the hippocampal formation in accordance to the emotional and motivational state of the animal, conveyed onto these cells by respective extrahippocampal afferents. Various excitatory and inhibitory afferent and efferent synapses of the hippocampal CCK basket cells express serotoninergic, cholinergic, cannabinoid, and benzodiazepine sensitive receptors, all contributing to their functional plasticity. We explored whether CCK basket cells are modulated by neuropeptide Y (NPY), one of the major local neuropeptides that strongly inhibits hippocampal excitability and has significant effect on its memory function. Here, using GAD65-GFP transgenic mice for prospective identification of CCK basket cells and whole-cell patch-clamp recordings, we show for the first time that excitatory and inhibitory inputs onto CCK basket cells in the dentate gyrus of the hippocampus are modulated by NPY through activation of NPY Y2 receptors. The frequency of spontaneous and miniature EPSCs, as well as the amplitudes of stimulation-evoked EPSCs were decreased. Similarly, the frequency of both spontaneous and miniature IPSCs, and the amplitudes of stimulation-evoked IPSCs were decreased after NPY application. Most of the effects of NPY could be attributed to a presynaptic site of action. Our data provide the first evidence that the excitatory and inhibitory inputs onto the CCK basket cells could be modulated by local levels of NPY, and may change the way these cells process extrahippocampal afferent information, influencing hippocampal function and its network excitability during normal and pathological oscillatory activities.
胆囊收缩素（CCK）表达篮状细胞包含一类抑制性 GABA 能中间神经元，根据动物的情绪和动机状态，调节海马结构中形成记忆的振荡网络活动，这些细胞通过各自的海马外传入神经传递信息。海马 CCK 篮状细胞的各种兴奋性和抑制性传入和传出突触表达 5-羟色胺能、胆碱能、大麻素和苯二氮䓬敏感受体，所有这些都有助于它们的功能可塑性。我们探讨了 CCK 篮状细胞是否受到神经肽 Y（NPY）的调节，NPY 是主要的局部神经肽之一，强烈抑制海马兴奋性，并对其记忆功能有显著影响。在这里，我们使用 GAD65-GFP 转基因小鼠对 CCK 篮状细胞进行前瞻性鉴定，并进行全细胞膜片钳记录，首次表明 NPY 通过激活 NPY Y2 受体调节海马齿状回 CCK 篮状细胞的兴奋性和抑制性输入。自发性和微小 EPSC 的频率，以及刺激诱发 EPSC 的幅度均降低。同样，应用 NPY 后，自发性和微小 IPSC 的频率以及刺激诱发 IPSC 的幅度均降低。NPY 的大部分作用可归因于突触前作用部位。我们的数据首次提供了证据，表明 CCK 篮状细胞的兴奋性和抑制性输入可以被局部 NPY 水平调节，并且可能改变这些细胞处理海马外传入信息的方式，影响海马功能及其在正常和病理振荡活动中的网络兴奋性。
