Experience-dependent functional adaptation of nucleus accumbens (NAc) circuitry underlies the development and expression of reward-motivated behaviors. Parvalbumin-expressing GABAergic (gamma-aminobutyric acidergic) interneurons (PVINs) within the NAc are required for this process. Perineuronal nets (PNNs) are extracellular matrix structures enriched around PVINs that arise during development and have been proposed to mediate brain circuit stability. However, their function in the adult NAc is largely unknown. Here, we studied the developmental emergence and adult regulation of PNNs in the NAc of male and female mice and examined the cellular and behavioral consequences of reducing the PNN component brevican in NAc PVINs. We characterized the expression of PNN components in mouse NAc using immunofluorescence and RNA in situ hybridization. We lowered brevican in NAc PVINs of adult mice using an intersectional viral and genetic method and quantified the effects on synaptic inputs to NAc PVINs and reward-motivated learning. PNNs around NAc PVINs were developmentally regulated and appeared during adolescence. In the adult NAc, PVIN PNNs were also dynamically regulated by cocaine. Transcription of the gene that encodes brevican was regulated in a cell type– and isoform-specific manner in the NAc, with the membrane-tethered form of brevican being highly enriched in PVINs. Lowering brevican in NAc PVINs of adult mice decreased their excitatory inputs and enhanced both short-term novel object recognition and cocaine-induced conditioned place preference. Regulation of brevican in NAc PVINs of adult mice modulates their excitatory synaptic drive and sets experience thresholds for the development of motivated behaviors driven by rewarding stimuli.

中文翻译：

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神经元周围网络蛋白 Brevican 在成年小鼠表达小清蛋白的伏核中间神经元中发挥作用，调节兴奋性突触输入和动机行为

伏隔核（NAc）电路的依赖于经验的功能适应是奖励驱动行为的发展和表达的基础。此过程需要 NAc 内表达小清蛋白的 GABA 能（γ-氨基丁酸能）中间神经元 (PVIN)。神经元周围网 (PNN) 是在 PVIN 周围富集的细胞外基质结构，在发育过程中出现，并被认为可以调节脑回路稳定性。然而，它们在成人 NAc 中的功能很大程度上未知。在这里，我们研究了雄性和雌性小鼠 NAc 中 PNN 的发育出现和成年调节，并检查了减少 NAc PVIN 中 PNN 成分 brevican 的细胞和行为后果。我们使用免疫荧光和 RNA 原位杂交表征了小鼠 NAc 中 PNN 成分的表达。我们使用交叉病毒和遗传方法降低了成年小鼠 NAc PVIN 中的短短聚糖，并量化了对 NAc PVIN 突触输入和奖励驱动学习的影响。 NAc PVIN 周围的 PNN 受到发育调节并在青春期出现。在成人 NAc 中，PVIN PNN 也受到可卡因的动态调节。编码 brevican 的基因的转录在 NAc 中以细胞类型和异构体特异性的方式受到调节，膜束缚形式的 brevican 在 PVIN 中高度富集。降低成年小鼠 NAc PVIN 中的短短聚糖可减少其兴奋性输入，并增强短期新物体识别和可卡因诱导的条件性位置偏好。成年小鼠 NAc PVIN 中短短聚糖的调节可调节其兴奋性突触驱动，并为奖励刺激驱动的动机行为的发展设定经验阈值。