School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, People's Republic of China.
State Key Laboratory of Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, People's Republic of China.
Brain Struct Funct. 2019 Mar;224(2):613-626. doi: 10.1007/s00429-018-1795-x. Epub 2018 Nov 20.
Perineuronal nets (PN) restrict neuronal plasticity in the adult brain. We hypothesize that activity-dependent consolidation of PN is required for functional maturation of behavioral circuits. Using the postnatal maturation of brainstem vestibular nucleus (VN) circuits as a model system, we report a neonatal period in which consolidation of central vestibular circuitry for graviception is accompanied by activity-dependent consolidation of chondroitin sulfate (CS)-rich PN around GABAergic neurons in the VN. Postnatal onset of negative geotaxis was used as an indicator for functional maturation of vestibular circuits. Rats display negative geotaxis from postnatal day (P) 9, coinciding with the condensation of CS-rich PN around GABAergic interneurons in the VN. Delaying PN formation, by removal of primordial CS moieties on VN with chondroitinase ABC (ChABC) treatment at P6, postponed emergence of negative geotaxis to P13. Similar postponement was observed following inhibition of GABAergic transmission with bicuculline, in line with the reported role of PN in increasing excitability of parvalbumin neurons. We further reasoned that PN-CS restricts bioavailability of plasticity-inducing factors such as semaphorin 3A (Sema3A) to bring about circuit maturation. Treatment of VN explants with ChABC to liberate PN-bound Sema3A resulted in dendritic growth and arborization, implicating structural plasticity that delays synapse formation. Evidence is thus provided for the role of PN-CS-Sema3A in regulating structural and circuit plasticity at VN interneurons with impacts on the development of graviceptive postural control.
周围神经毡（PN）限制成年大脑中的神经元可塑性。我们假设，PN 的活性依赖性巩固对于行为回路的功能成熟是必需的。使用脑干前庭核（VN）回路的出生后成熟作为模型系统，我们报告了一个新生儿期，在此期间，重力感受的中枢前庭回路的巩固伴随着软骨素硫酸盐（CS）丰富的 PN 在 VN 中的 GABA 能神经元周围的活性依赖性巩固。负向趋地性的出现被用作前庭回路功能成熟的指标。大鼠从出生后第 9 天（P）开始表现出负向趋地性，这与 CS 丰富的 PN 在 VN 中的 GABA 能中间神经元周围凝聚相吻合。通过在 P6 时用软骨素酶 ABC（ChABC）处理 VN 去除原始 CS 部分来延迟 PN 的形成，将负向趋地性推迟到 P13。在用 Bicuculline 抑制 GABA 能传递时观察到类似的延迟，这与 PN 增加副球蛋白神经元兴奋性的报道作用一致。我们进一步推断，PN-CS 限制了可塑性诱导因子（如神经丝蛋白 3A（Sema3A））的生物利用度，从而实现回路成熟。用 ChABC 处理 VN 外植体以释放与 PN 结合的 Sema3A 导致树突生长和分支，暗示结构可塑性延迟了突触形成。因此，提供了 PN-CS-Sema3A 在调节 VN 中间神经元的结构和回路可塑性中的作用的证据，这对重力感受姿势控制的发展有影响。
