Rhythmically active enkephalin-expressing GABAergic cells in the CA1 area of the hippocampus project to the subiculum and preferentially innervate interneurons.
Rhythmically active enkephalin-expressing GABAergic cells in the CA1 area of the hippocampus project to the subiculum and preferentially innervate interneurons.
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DOI：
10.1523/jneurosci.2052-08.2008
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发表时间：
2008-10-01
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影响因子：
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通讯作者：
Somogyi P
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文献类型：
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作者：
Fuentealba P;Tomioka R;Dalezios Y;Márton LF;Studer M;Rockland K;Klausberger T;Somogyi P
脑啡肽 (ENK) 是内源性阿片类药物，可调节大脑皮层 GABA 网络的突触兴奋性。通过在下托中逆行示踪剂注射，我们鉴定了海马表达 ENK 的投射神经元群。 GAD 原位杂交表明表达 ENK 的细胞是一个小的 GABA 能亚群。此外，通过细胞外记录和体内细胞旁标记，我们通过其完整的轴突树状结构和网络振荡期间的特征性尖峰计时，在 CA1 区域的放射层中鉴定了表达 ENK 的细胞。体细胞树突膜 mGluR1α 免疫阳性，CA1 区有丰富的局部轴突和下突分支。纽扣显示出细胞类型和层特异性的神经支配，即中间神经元是肺泡中的主要目标，中间神经元和锥体细胞树突在其他层中都受到神经支配，而中间神经元是下托中的唯一目标。表达小清蛋白的中间神经元是首选的突触靶标，但表达生长抑素、钙结合蛋白或胆囊收缩素的中间神经元不是。在网络活动期间，近细胞标记的 ENK 表达细胞在整个 θ 振荡过程中进行相位调制，但在尖波/波纹事件期间保持沉默。在这些事件之后，中间神经元表现出高频尖峰爆发的反弹活动，可能导致肽释放。表达 ENK 的中间神经元支配小清蛋白阳性中间神经元，可能通过在波纹发作期间减少放电和在波纹发作后反弹活动来促进尖波/波纹发作的组织，以及在网络振荡期间协调 CA1 和皮下区域之间的活动。
Enkephalins (ENKs) are endogenous opioids that regulate synaptic excitability of GABAergic networks in the cerebral cortex. Using retrograde tracer injections in the subiculum, we identified a hippocampal population of ENK-expressing projection neurons. In situ hybridization for GAD shows that ENK-expressing cells are a small GABAergic subpopulation. Furthermore, by extracellular recording and juxtacellular labeling in vivo, we identified an ENK-expressing cell in stratum radiatum of the CA1 area by its complete axodendritic arborization and characteristic spike timing during network oscillations. The somatodendritic membrane was immunopositive for mGluR1α, and there was both a rich local axon in CA1 and subicular-projecting branches. The boutons showed cell-type- and layer-specific innervation, i.e., interneurons were the main targets in the alveus, both interneurons and pyramidal cell dendrites were innervated in the other layers, and interneurons were exclusive targets in the subiculum. Parvalbumin-, but not somatostatin-, calbindin-, or cholecystokinin-expressing interneurons were preferred synaptic targets. During network activity, the juxtacellularly labeled ENK-expressing cell was phase modulated throughout theta oscillations, but silenced during sharp-wave/ripple episodes. After these episodes the interneuron exhibited rebound activity of high-frequency spike bursts, presumably causing peptide release. The ENK-expressing interneurons innervating parvalbumin-positive interneurons might contribute to the organization of the sharp-wave/ripple episodes by decreased firing during and rebound activity after the ripple episodes, as well as to the coordination of activity between the CA1 and subicular areas during network oscillations.