瑞士巴塞尔大学Peter Scheiffele研究组发现，BMP-SMAD1信号对神经元兴奋-抑制平衡的控制。这一研究成果于2024年4月17日在线发表在国际学术期刊《自然》上。

研究人员在成年小鼠的新皮层中发现了一种信号通路，这种通路会随着神经元网络活动的增加而被激活。兴奋性神经元的过度激活是通过BMP2水平的增加向网络发出信号的，BMP2是一种生长因子，因其在胚胎发育过程中作为形态发生因子的作用而广为人知。BMP2通过转录因子SMAD1作用于表达小清蛋白（PV）的中间神经元，SMAD1控制着一系列谷氨酸能突触蛋白和神经元周围网络的成分。

BMP2-SMAD1信号在中枢神经间元特异性中断后，中枢神经间元细胞中的谷氨酸能神经支配会丧失，神经元周围网发育不全，兴奋性降低。最终，PV中间神经元功能招募的这种损害破坏了大脑皮层的兴奋-抑制平衡，小鼠表现出自发性癫痫发作。研究结果表明，发育过程中的形态发生信号被重新用于稳定成年哺乳动物大脑皮层网络。

研究人员表示，在整个生命过程中，哺乳动物新皮层中的神经元网络一直保持着兴奋和抑制的平衡，这对神经元计算至关重要。偏离平衡状态与神经发育障碍有关，严重破坏则会导致癫痫。为了保持平衡，由兴奋性和抑制性神经元组成的神经元微回路会感知神经活动的变化，并调整神经元的连接和功能。

附：英文原文

Title: Control of neuronal excitation–inhibition balance by BMP–SMAD1 signalling

Author: Okur, Zeynep, Schlauri, Nadia, Bitsikas, Vassilis, Panopoulou, Myrto, Ortiz, Raul, Schwaiger, Michaela, Karmakar, Kajari, Schreiner, Dietmar, Scheiffele, Peter

Issue&Volume: 2024-04-17

Abstract: Throughout life, neuronal networks in the mammalian neocortex maintain a balance of excitation and inhibition, which is essential for neuronal computation1,2. Deviations from a balanced state have been linked to neurodevelopmental disorders, and severe disruptions result in epilepsy3,4,5. To maintain balance, neuronal microcircuits composed of excitatory and inhibitory neurons sense alterations in neural activity and adjust neuronal connectivity and function. Here we identify a signalling pathway in the adult mouse neocortex that is activated in response to increased neuronal network activity. Overactivation of excitatory neurons is signalled to the network through an increase in the levels of BMP2, a growth factor that is well known for its role as a morphogen in embryonic development. BMP2 acts on parvalbumin-expressing (PV) interneurons through the transcription factor SMAD1, which controls an array of glutamatergic synapse proteins and components of perineuronal nets. PV-interneuron-specific disruption of BMP2–SMAD1 signalling is accompanied by a loss of glutamatergic innervation in PV cells, underdeveloped perineuronal nets and decreased excitability. Ultimately, this impairment of the functional recruitment of PV interneurons disrupts the cortical excitation–inhibition balance, with mice exhibiting spontaneous epileptic seizures. Our findings suggest that developmental morphogen signalling is repurposed to stabilize cortical networks in the adult mammalian brain.

DOI: 10.1038/s41586-024-07317-z

Source: https://www.nature.com/articles/s41586-024-07317-z