McElroy Dan L, Barnard Ilne L, Glass Aiden E, Young Kaylen M, Kryachko Veronica, Botterill Justin J, Howland John G
Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon S7N 5E5, Canada.
Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon S7N 5E5, Canada.
Neurobiol Learn Mem. 2025 May;219:108055. doi: 10.1016/j.nlm.2025.108055. Epub 2025 Apr 19.
Previous research suggests ionotropic glutamate receptors in anterior retrosplenial cortex (aRSC) are important for short-term (1-hour) object-in-place (OiP) novelty recognition, indicated by enhanced interaction with novel object-location pairs during OiP test phases. Here, male and female rats were repeatedly tested in three 1-hour delay novelty recognition tests: object recognition (OR), object location (OL), and OiP. Prior to behavioral testing, control (AAV5-CaMKIIα-mCherry) or active (AAV5-CaMKIIα-hM4D(Gi)-mCherry) viral vectors were bilaterally infused into the aRSC of male (8 control, 13 active) and female (8 control, 13 active) Long Evans rats, enabling selective inhibition of aRSC neurons with the hM4D agonist Compound 21 (C-21). Following recovery from surgery, rats were repeatedly tested in recognition tests following injection of either saline or C-21 (1.0 mg/kg; i.p.) ∼45-min prior to test phases (6 tests/rat). Analyses of exploration times indicated that total object interaction times did not differ between phase, sex, or treatment. Further analyses revealed that C-21 treatment of rats infused with the active vector reduced novelty recognition in the OR test yet had no influence in the OL test, regardless of sex. Interestingly, C-21 also reduced novelty recognition in OiP recognition test phases, an effect only observed in male rats infused with the active vector. Findings highlight a nuanced influence of aRSC neurons in supporting novelty recognition which varies by sex and type of stimuli assayed.
先前的研究表明，前扣带回后皮质（aRSC）中的离子型谷氨酸受体对于短期（1小时）物体位置（OiP）新奇识别很重要，这在OiP测试阶段与新颖物体 - 位置对的增强相互作用中得到体现。在此，对雄性和雌性大鼠进行了三次1小时延迟新奇识别测试的重复测试：物体识别（OR）、物体位置（OL）和OiP。在行为测试之前，将对照（AAV5 - CaMKIIα - mCherry）或活性（AAV5 - CaMKIIα - hM4D(Gi) - mCherry）病毒载体双侧注入雄性（8只对照，13只活性）和雌性（8只对照，13只活性）Long Evans大鼠的aRSC中，从而能够用hM4D激动剂化合物21（C - 21）选择性抑制aRSC神经元。手术后恢复后，在测试阶段前约45分钟注射生理盐水或C - 21（1.0 mg/kg；腹腔注射）后，对大鼠进行重复的识别测试（每只大鼠6次测试）。探索时间分析表明，物体总相互作用时间在阶段、性别或处理之间没有差异。进一步分析显示，用活性载体注入的大鼠接受C - 21处理后，在OR测试中降低了新奇识别能力，但在OL测试中没有影响，无论性别如何。有趣的是，C - 21在OiP识别测试阶段也降低了新奇识别能力，这种效应仅在注入活性载体的雄性大鼠中观察到。研究结果突出了aRSC神经元在支持新奇识别方面的细微影响，这种影响因性别和所检测刺激的类型而异。
