Obray J Daniel, Denton Adam R, Carroll-Deaton Jayda, Marquardt Kristin, Chandler L Judson, Scofield Michael D
Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425.
Department of Anesthesiology and Perioperative Medicine, Medical University of South Carolina, Charleston, SC 29425.
bioRxiv. 2024 Oct 23:2024.10.23.619810. doi: 10.1101/2024.10.23.619810.
Perineuronal nets (PNNs) are specialized components of the extracellular matrix that play a critical role in learning and memory. In a Pavlovian fear conditioning paradigm, degradation of PNNs affects the formation and storage of fear memories. This study examined the impact of adolescent intermittent ethanol (AIE) exposure by vapor inhalation on the expression of PNNs in the adult rat prelimbic (PrL) and infralimbic (IfL) subregions of the medial prefrontal cortex. Results indicated that following AIE, the total number of PNN positive cells in the PrL cortex increased in layer II/III but did not change in layer V. Conversely, in the IfL cortex, the number of PNN positive cells decreased in layer V, with no change in layer II/III. In addition, the intensity of PNN staining was significantly altered by AIE exposure, which narrowed the distribution of signal intensity, reducing the number of high and low intensity PNNs. Given these changes in PNNs, the next experiment assessed the effects of AIE and PNN digestion on extinction of a conditioned fear memory. In Air control rats, digestion of PNNs by bilateral infusion of Chondroitinase ABC (ChABC) into the IfL cortex enhanced fear extinction and reduced contextual fear renewal. In contrast, both fear extinction learning and contextual fear renewal remained unchanged following PNN digestion in AIE exposed rats. These results highlight the sensitivity of prefrontal PNNs to adolescent alcohol exposure and suggest that ChABC-induced plasticity is reduced in the IfL cortex following AIE exposure.
神经元周围网络（PNNs）是细胞外基质的特殊组成部分，在学习和记忆中起着关键作用。在巴甫洛夫恐惧条件反射范式中，PNNs的降解会影响恐惧记忆的形成和存储。本研究通过蒸汽吸入法检测青少年间歇性乙醇（AIE）暴露对成年大鼠内侧前额叶皮质前边缘（PrL）和下边缘（IfL）亚区PNNs表达的影响。结果表明，AIE暴露后，PrL皮质II/III层中PNN阳性细胞总数增加，而V层未发生变化。相反，在IfL皮质中，V层PNN阳性细胞数量减少，II/III层无变化。此外，AIE暴露显著改变了PNN染色强度，使信号强度分布变窄，减少了高强度和低强度PNN的数量。鉴于PNNs的这些变化，接下来的实验评估了AIE和PNN消化对条件性恐惧记忆消退的影响。在空气对照组大鼠中，通过向IfL皮质双侧注射软骨素酶ABC（ChABC）消化PNNs可增强恐惧消退并减少情境性恐惧恢复。相比之下，AIE暴露大鼠在PNN消化后，恐惧消退学习和情境性恐惧恢复均未改变。这些结果突出了前额叶PNNs对青少年酒精暴露的敏感性，并表明AIE暴露后IfL皮质中ChABC诱导的可塑性降低。
