Department of Neuroscience, Rockefeller Neuroscience Institute, WVU, 33 Medical Center Dr, Morgantown, WV 26505, United States.
Department of Neuroscience, Rockefeller Neuroscience Institute, WVU, 33 Medical Center Dr, Morgantown, WV 26505, United States.
Neurobiol Learn Mem. 2021 Jan;177:107358. doi: 10.1016/j.nlm.2020.107358. Epub 2020 Dec 4.
The perineuronal net (PNN) is a specialized type of extracellular matrix found in the central nervous system. The PNN forms on fast spiking neurons during postnatal development but the ontogeny of PNN development has yet to be elucidated. By studying the development and prevalence of the PNN in the juvenile and adult rat brain, we may be able to understand the PNN's role in development and learning and memory. We show that the PNN is fully developed in the deep cerebellar nuclei (DCN) of rats by P18. By using enzymatic digestion of the PNN with chondroitinase ABC (ChABC), we are able to study how digestion of the PNN affects cerebellar-dependent eyeblink conditioning in vivo and perform electrophysiological recordings from DCN neurons in vitro. In vivo degradation of the PNN resulted in significant differences in eyeblink conditioning amplitude and area. Female animals in the vehicle group demonstrated higher levels of conditioning as well as significantly higher post-probe conditioned responses compared to males in that group, differences not present in the ChABC group. In vitro, we found that DCN neurons with a disrupted PNN following exposure to ChABC had altered membrane properties, fewer rebound spikes, and decreased intrinsic excitability. Together, this study further elucidates the role of the PNN in cerebellar learning in the DCN and is the first to demonstrate PNN degradation may erase sex differences in delay conditioning.
周围神经毡（PNN）是中枢神经系统中一种特殊类型的细胞外基质。PNN 在出生后发育过程中形成于快速放电神经元上，但 PNN 发育的个体发生尚未阐明。通过研究幼年和成年大鼠大脑中 PNN 的发育和流行情况，我们或许能够理解 PNN 在发育、学习和记忆中的作用。我们发现，PNN 在 P18 时已在大鼠的小脑深部核团（DCN）中完全发育。通过使用软骨素酶 ABC（ChABC）消化 PNN，我们能够研究 PNN 的消化如何影响体内小脑依赖的眨眼条件反射，并对 DCN 神经元进行体外电生理记录。体内 PNN 的降解导致眨眼条件反射幅度和面积的显著差异。与该组中的雄性动物相比，在载体组中的雌性动物表现出更高水平的条件反射以及显著更高的探测后条件反射反应，而在 ChABC 组中则不存在这些差异。在体外，我们发现，在接触 ChABC 后 PNN 被破坏的 DCN 神经元具有改变的膜特性、较少的反弹 spikes 以及降低的内在兴奋性。总的来说，这项研究进一步阐明了 PNN 在 DCN 小脑学习中的作用，并且是首次表明 PNN 降解可能消除延迟条件反射中的性别差异。
