Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Neurobiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Center for Brain Science of Shanghai Children's Medical Center, Department of Anatomy and Physiology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Sci Adv. 2024 Aug 2;10(31):eadk4331. doi: 10.1126/sciadv.adk4331.
Homeostatic plasticity maintains the stability of functional brain networks. The axon initial segment (AIS), where action potentials start, undergoes dynamic adjustment to exert powerful control over neuronal firing properties in response to network activity changes. However, it is poorly understood whether this plasticity involves direct synaptic input to the AIS. Here, we show that changes of GABAergic synaptic input from chandelier cells (ChCs) drive homeostatic tuning of the AIS of principal neurons (PNs) in the prelimbic (PL) region, while those from parvalbumin-positive basket cells do not. This tuning is evident in AIS morphology, voltage-gated sodium channel expression, and PN excitability. Moreover, the impact of this homeostatic plasticity can be reflected in animal behavior. Social behavior, inversely linked to PL PN activity, shows time-dependent alterations tightly coupled to changes in AIS plasticity and PN excitability. Thus, AIS-originated homeostatic plasticity in PNs may counteract deficits elicited by imbalanced ChC presynaptic input at cellular and behavioral levels.
稳态可塑性维持着功能大脑网络的稳定性。动作电位起始的轴突起始段（AIS）会发生动态调整，以对神经元放电特性施加强大的控制，从而响应网络活动的变化。然而，目前尚不清楚这种可塑性是否涉及到 AIS 的直接突触输入。在这里，我们表明，来自篮状细胞（ChC）的 GABA 能突触输入的变化驱动了前额叶皮层（PL）区域主神经元（PN）的 AIS 的稳态调节，而来自 Parvalbumin 阳性 basket 细胞的输入则没有。这种调节在 AIS 形态、电压门控钠通道表达和 PN 兴奋性中都很明显。此外，这种稳态可塑性的影响可以在动物行为中得到反映。与 PL PN 活性呈反比的社交行为表现出与 AIS 可塑性和 PN 兴奋性变化紧密耦合的时变改变。因此，PN 中的 AIS 起源的稳态可塑性可能在细胞和行为水平上抵消由 ChC 突触前输入失衡引起的缺陷。
