Albayram Önder, Passlick Stefan, Bilkei-Gorzo Andras, Zimmer Andreas, Steinhäuser Christian
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Sigmund-Freud Str. 25, 53105, Bonn, Germany.
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Sigmund-Freud Str. 25, 53105, Bonn, Germany.
Pflugers Arch. 2016 Apr;468(4):727-37. doi: 10.1007/s00424-015-1782-5. Epub 2016 Jan 7.
A subset of hippocampal GABAergic neurons, which are cholecystokinin-positive, highly express cannabinoid type 1 (CB1) receptors. Activation of these receptors inhibits GABA release and thereby limits inhibitory control. While genetic deletion of CB1 receptors from GABAergic neurons led to behavioural alterations and neuroinflammatory reactions, it remained unclear whether these changes in the knockout animals were a direct consequence of the enhanced transmitter release or reflected developmental deficits. The hippocampus is vital for the generation of spatial, declarative and working memory. Here, we addressed the question how CB1 receptors in GABAergic neurons influence hippocampal function. Patch clamp and field potential recordings in mice devoid of CB1 receptors in GABAergic neurons revealed an enhanced frequency and faster kinetics of spontaneous inhibitory postsynaptic currents in CA1 pyramidal neurons while tonic inhibition, paired-pulse facilitation and long-term potentiation in the hippocampus were not affected. Evaluation of cognitive functions demonstrated impaired acquisition of spatial memory and deficits in novel object recognition and partner recognition in the knockout mice, while working memory and spatial memory remained intact. The density of GABAergic neurons was also similar in knockout mice and their littermates, which argues against global deficits in hippocampal development. Together, these results suggest that CB1 receptors in GABAergic neurons influence specific aspects of neuronal excitability and hippocampal learning.
海马体中一部分胆囊收缩素阳性的γ-氨基丁酸能神经元高度表达1型大麻素（CB1）受体。这些受体的激活会抑制γ-氨基丁酸的释放，从而限制抑制性控制。虽然从γ-氨基丁酸能神经元中基因敲除CB1受体会导致行为改变和神经炎症反应，但尚不清楚基因敲除动物的这些变化是递质释放增强的直接后果还是反映了发育缺陷。海马体对于空间记忆、陈述性记忆和工作记忆的形成至关重要。在此，我们探讨了γ-氨基丁酸能神经元中的CB1受体如何影响海马体功能这一问题。对γ-氨基丁酸能神经元中缺乏CB1受体的小鼠进行膜片钳和场电位记录发现，CA1锥体神经元中自发抑制性突触后电流的频率增加且动力学加快，而海马体中的强直抑制、双脉冲易化和长时程增强不受影响。对认知功能的评估表明，基因敲除小鼠在空间记忆获取、新物体识别和伙伴识别方面存在缺陷，而工作记忆和空间记忆保持完整。基因敲除小鼠及其同窝小鼠的γ-氨基丁酸能神经元密度也相似，这排除了海马体发育存在整体缺陷的可能性。总之，这些结果表明γ-氨基丁酸能神经元中的CB1受体影响神经元兴奋性和海马体学习的特定方面。
