Krüssel Sarah, Deb Ishana, Son Seungkyu, Ewall Gabrielle, Chang Minhyeok, Lee Hey-Kyoung, Heo Won Do, Kwon Hyung-Bae
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
iScience. 2024 Jul 18;27(8):110535. doi: 10.1016/j.isci.2024.110535. eCollection 2024 Aug 16.
Dendritic protrusions, mainly spines and filopodia, correlate with excitatory synapses in pyramidal neurons (PyNs), but this relationship may not apply universally. We found that ectopic H-Ras expression increased protrusions across various cortical cell types, including layer 2/3 PyNs, parvalbumin (PV)-, and vasoactive intestinal peptide (VIP)-positive interneurons (INs) in the primary motor cortex. The probability of detecting protrusions correlated with local H-Ras activity, indicating its role in protrusion formation. H-Ras overexpression led to high turnover rates by adding protrusions. Two-photon photolysis of glutamate induced spine formation in mature H-Ras expressing neurons, suggesting H-Ras's effect is not limited to early development. In PyNs and PV-INs, but not VIP-INs, spine neck lengths shifted to filopodia-like phenotypes. H-Ras primarily induced filopodia in PyNs and spines in PV- and VIP-INs. Increased protrusions in H-Ras-transfected PyNs lacked key excitatory synaptic proteins and did not affect miniature excitatory postsynaptic currents (mEPSCs), suggesting multifaceted roles beyond excitatory synapses.
树突状突起，主要是棘突和丝状伪足，与锥体神经元（PyNs）中的兴奋性突触相关，但这种关系可能并不普遍适用。我们发现，异位表达H-Ras会增加多种皮质细胞类型中的突起，包括初级运动皮层中的第2/3层锥体神经元、小白蛋白（PV）和血管活性肠肽（VIP）阳性中间神经元（INs）。检测到突起的概率与局部H-Ras活性相关，表明其在突起形成中的作用。H-Ras过表达通过增加突起导致高更新率。谷氨酸的双光子光解在成熟的表达H-Ras的神经元中诱导棘突形成，表明H-Ras的作用不限于早期发育。在锥体神经元和PV-中间神经元中，但不在VIP-中间神经元中，棘突颈部长度转变为丝状伪足样表型。H-Ras主要在锥体神经元中诱导丝状伪足，在PV-和VIP-中间神经元中诱导棘突。在H-Ras转染的锥体神经元中增加的突起缺乏关键的兴奋性突触蛋白，并且不影响微小兴奋性突触后电流（mEPSCs），表明其在兴奋性突触之外具有多方面的作用。
