Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, 10043, Orbassano, Turin, Italy; Department of Neuroscience, University of Turin, 10126, Turin, Italy; Neuroscience Institute of Turin (NIT), Italy.
Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, 10043, Orbassano, Turin, Italy; Department of Neuroscience, University of Turin, 10126, Turin, Italy.
Neuropharmacology. 2021 Feb 15;184:108425. doi: 10.1016/j.neuropharm.2020.108425. Epub 2020 Dec 4.
Perineuronal nets (PNNs) are extracellular matrix structures that form around some types of neurons at the end of critical periods, limiting neuronal plasticity. In the adult brain, PNNs play a crucial role in the regulation of learning and cognitive processes. Neuropeptide Y (NPY) is involved in the regulation of many physiological functions, including learning and memory abilities, via activation of Y1 receptors (Y1Rs). Here we demonstrated that the conditional depletion of the gene encoding the Y1R for NPY in adult forebrain excitatory neurons (Npy1r mutant mice), induces a significant slowdown in spatial learning, which is associated with a robust intensification of PNN expression and an increase in the number of c-Fos expressing cells in the cornus ammonis 1 (CA1) of the dorsal hippocampus. Importantly, the enzymatic digestion of PNNs in CA1 normalizes c-Fos activity and completely rescues learning abilities of Npy1r mice. These data highlight a previously unknown functional link between NPY-Y1R transmission and PNNs, which may play a role in the control of dorsal hippocampal excitability and related cognitive functions.
周围神经毡（PNNs）是细胞外基质结构，在关键期结束时围绕某些类型的神经元形成，限制神经元的可塑性。在成年大脑中，PNNs 在学习和认知过程的调节中起着至关重要的作用。神经肽 Y（NPY）通过激活 Y1 受体（Y1Rs）参与许多生理功能的调节，包括学习和记忆能力。在这里，我们证明了在成年大脑兴奋性神经元中条件性敲除编码 NPY 的 Y1R 的基因（Npy1r 突变小鼠），会导致空间学习明显减慢，这与 PNN 表达的强烈增强以及背侧海马 CA1 中 c-Fos 表达细胞数量的增加有关。重要的是，CA1 中 PNN 的酶消化使 c-Fos 活性正常化，并完全挽救了 Npy1r 小鼠的学习能力。这些数据突出了 NPY-Y1R 传递和 PNNs 之间以前未知的功能联系，这可能在控制背侧海马兴奋性和相关认知功能中发挥作用。
