Brewer Logan M, Patel Jankiben, Andrasik Frank, Sable Jeffrey J, Williams Michael T, Vorhees Charles V, Sable Helen J K
Department of Psychology, 202 Psychology Building, University of Memphis, Memphis, TN 38152, USA.
Department of Behavioral Sciences and Neuroscience Program, Christian Brothers University, Memphis, TN 38104, USA.
Genes (Basel). 2025 May 30;16(6):672. doi: 10.3390/genes16060672.
BACKGROUND/OBJECTIVES: Variations of the latrophilin-3 () gene have been associated with attention-deficit hyperactivity disorder (ADHD). To explore the functional influence of this gene, knockout (KO) rats were generated and have thus far demonstrated deficits in ADHD-relevant phenotypes, including working memory, impulsivity, and hyperactivity. However, inattention remains unexplored.
We assessed automatic attention in KO (n = 19) and their control line (wildtype/WT, n = 20) through use of the following auditory event-related potentials (ERPs): P1, N1, P2, and N2. We also extended this exploratory study by comparing these same ERPs in spontaneously hypertensive rats (SHRs, n = 16), the most commonly studied animal model of ADHD, to their control line (Wistar-Kyoto/WKY, n = 20). Electroencephalograms (EEG) were recorded using subdermal needle electrodes at frontocentral sites while freely moving rats were presented with five-tone trains (50 ms tones, 400 ms tone onset asynchronies) with varying short (1 s) and long (5 s) inter-train intervals. Peak amplitudes and latencies were analyzed using GLM-mixed ANOVAs to assess differences across genotypes (KO vs. WTs) and strains (SHRs vs. WKYs).
The KOs did not demonstrate any significant differences in peak amplitudes relative to the WT controls, suggesting that the null expression of does not result in the development of inefficiencies in automatic attention. However, the SHRs exhibited significantly reduced peak P1 (and peak-to-peak P1-N1) values relative to the WKYs. These attenuations likely reflect inefficiencies in bottom-up arousal networks that are necessary for efficient automatic processing.
Distinct findings between these animal models likely reflect differing alterations in dopamine and noradrenaline neurotransmission that may underlie ADHD-relevant phenotypes.
背景/目的：促离子型受体3（）基因的变异与注意力缺陷多动障碍（ADHD）有关。为了探究该基因的功能影响，我们构建了基因敲除（KO）大鼠，目前已证明其在与ADHD相关的表型上存在缺陷，包括工作记忆、冲动性和多动。然而，注意力不集中仍未得到研究。
我们通过使用以下听觉事件相关电位（ERP）评估了基因敲除大鼠（n = 19）及其对照品系（野生型/WT，n = 20）的自动注意力：P1、N1、P2和N2。我们还通过比较自发性高血压大鼠（SHRs，n = 16）及其对照品系（Wistar-Kyoto/WKY，n = 20）的相同ERP，扩展了这项探索性研究。SHRs是最常被研究的ADHD动物模型。在大鼠自由活动时，使用皮下针电极在前额中央部位记录脑电图（EEG），同时向它们呈现具有不同短（1秒）和长（5秒）串间间隔的五音序列（50毫秒音调，400毫秒音调起始异步）。使用广义线性模型混合方差分析（GLM-mixed ANOVAs）分析峰值幅度和潜伏期，以评估不同基因型（基因敲除大鼠与野生型）和品系（SHRs与WKYs）之间的差异。
与野生型对照相比，基因敲除大鼠在峰值幅度上没有表现出任何显著差异，这表明基因的无效表达不会导致自动注意力效率低下。然而，与WKYs相比，SHRs的峰值P1（以及峰峰值P1-N1）值显著降低。这些衰减可能反映了自下而上的唤醒网络效率低下，而这对于高效的自动处理是必要的。
这些动物模型之间的不同发现可能反映了多巴胺和去甲肾上腺素神经传递的不同改变，这些改变可能是与ADHD相关表型的基础。
