Homeostatic plasticity plays important role in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), the early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes related to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma—the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, when IOP rises. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in 9-month-old D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner. These data suggest that glaucoma-associated changes to neuronal excitability and synaptic inputs in the dLGN might represent a combination of both stabilizing/homeostatic plasticity and pathological dysfunction.

稳态可塑性在调节突触和固有神经元功能以稳定电路活动后的输出中起重要作用。青光眼是一种视觉系统的神经退行性疾病，通常与眼内压（IOP）升高有关，早期疾病与视网膜神经节细胞（RGC）的突触输入改变，RGC内在兴奋性变化以及视神经运输和功能障碍有关。能量代谢。这些早期的功能改变可以在RGC变性之前发生，并可能改变RGC输出到大脑中的目标结构，从而触发这些大脑区域的突触和神经元特性的稳态变化。在这个研究中，我们试图确定是否以及如何改变背外侧膝状核（dLGN），丘脑中重要的RGC投射靶标的神经元和突触功能，以及功能变化如何与IOP相关。我们在两个已建立的青光眼小鼠模型（DBA / 2J（D2）遗传小鼠模型和可诱导性青光眼模型中，通过前房内微珠注射以提高IOP）中dLGN中的丘脑皮质（TC）中继神经元的膜片钳记录来实现这一目的。我们发现TC神经元的内在兴奋性在D2小鼠中得到增强，并且这些功能的变化反映在注射微珠小鼠的TC神经元的记录中。值得注意的是，当IOP升高时，许多D2小鼠的神经元特性与IOP相关。在9个月大的D2小鼠中，微型兴奋性突触电流（mEPSC）的频率降低，而RGC突触末端的vGlut2染色以IOP依赖性方式降低。这些数据表明，dLGN中与青光眼相关的神经元兴奋性变化和突触输入可能代表了稳定/体内可塑性和病理功能障碍。