Institut Pasteur, Université Paris Cité, Neural Circuits for Space and Memory, Department of Neuroscience, Paris F-75015, France.
Institute for Physiology I, Jena University Hospital, Jena 07743, Germany.
Proc Natl Acad Sci U S A. 2024 Nov 5;121(45):e2403325121. doi: 10.1073/pnas.2403325121. Epub 2024 Oct 28.
The hippocampus is a brain region that is essential for the initial encoding of episodic memories. However, the consolidation of these memories is thought to occur in the neocortex, under guidance of the hippocampus, over the course of days and weeks. Communication between the hippocampus and the neocortex during hippocampal sharp wave-ripple oscillations is believed to be critical for this memory consolidation process. Yet, the synaptic and circuit basis of this communication between brain areas is largely unclear. To address this problem, we perform in vivo whole-cell patch-clamp recordings in the frontal neocortex and local field potential recordings in CA1 of head-fixed mice exposed to a virtual-reality environment. In mice trained in a goal-directed spatial task, we observe a depolarization in frontal principal neurons during hippocampal ripple oscillations. Both this ripple-associated depolarization and goal-directed task performance can be disrupted by chemogenetic inactivation of somatostatin-positive (SOM) interneurons. In untrained mice, a ripple-associated depolarization is not observed, but it emerges when frontal parvalbumin-positive (PV) interneurons are inactivated. These results support a model where SOM interneurons inhibit PV interneurons during hippocampal activity, thereby acting as a disinhibitory gate for hippocampal inputs to neocortical principal neurons during learning.
海马体是大脑中对情景记忆的初步编码至关重要的区域。然而，人们认为这些记忆的巩固是在海马体的指导下，在数天和数周的时间里在新皮层中进行的。海马体尖锐波 - 涟漪振荡期间海马体和新皮层之间的通信被认为对这个记忆巩固过程至关重要。然而，大脑区域之间这种通信的突触和电路基础在很大程度上还不清楚。为了解决这个问题，我们在暴露于虚拟现实环境的头部固定小鼠的额皮质中进行了体内全细胞膜片钳记录，并在 CA1 中进行了局部场电位记录。在接受目标导向空间任务训练的小鼠中，我们观察到海马体涟漪振荡期间额皮质主神经元的去极化。这种与涟漪相关的去极化以及目标导向任务的表现都可以通过化学遗传失活生长抑素阳性（SOM）中间神经元来破坏。在未经训练的小鼠中，观察不到与涟漪相关的去极化，但当抑制性中间神经元失活时，它会出现。这些结果支持这样一种模型，即 SOM 中间神经元在海马体活动期间抑制 PV 中间神经元，从而在学习期间充当海马体输入到新皮质主神经元的去抑制门。
