Outram Alexandra R, Brown Malcolm W, Warburton Elizabeth Clea, Barker Gareth R I
School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.
Front Behav Neurosci. 2022 Oct 3;16:970291. doi: 10.3389/fnbeh.2022.970291. eCollection 2022.
Object recognition, the ability to discriminate between a novel and a familiar stimulus, is critically dependent upon the perirhinal cortex. Neural response reductions upon repetition of a stimulus, have been hypothesized to be the mechanism within perirhinal cortex that supports recognition memory function. Thus, investigations into the mechanisms of long-term depression (LTD) in perirhinal cortex has provided insight into the mechanism of object recognition memory formation, but the contribution of long-term potentiation (LTP) to object recognition memory formation has been less studied. Inhibition of atypical PKC activity by Zeta Inhibitory Pseudosubstrate (ZIP) impairs the maintenance of LTP but not LTD, thus here infusion of ZIP into the perirhinal cortex allowed us to investigate the contribution of LTP-like mechanisms to object recognition memory maintenance. Infusion of ZIP into the perirhinal cortex of rats 24 h after the sample phase impaired performance in an object recognition but not an object location task, in contrast infusion of ZIP into the hippocampus impaired performance in an object location but not an object recognition task. The impairment in object recognition by ZIP was prevented by administration of the peptide GluA2, which blocks the endocytosis of GluA2 containing AMPA receptors. Finally, performance in a perceptual oddity task, which requires perirhinal cortex function, was not disrupted by ZIP. Together these results demonstrate the importance of LTP-like mechanisms to the maintenance of object recognition memory in the perirhinal cortex.
物体识别,即区分新刺激和熟悉刺激的能力,严重依赖于内嗅皮质。刺激重复时神经反应的减弱,被认为是内嗅皮质中支持识别记忆功能的机制。因此,对内嗅皮质中长期抑制(LTD)机制的研究为物体识别记忆形成的机制提供了见解,但长期增强(LTP)对物体识别记忆形成的贡献研究较少。Zeta抑制性假底物(ZIP)对非典型蛋白激酶C活性的抑制会损害LTP的维持,但不会损害LTD,因此在这里将ZIP注入内嗅皮质使我们能够研究类似LTP的机制对物体识别记忆维持的贡献。在样本阶段后24小时将ZIP注入大鼠的内嗅皮质,会损害物体识别任务的表现,但不会损害物体位置任务的表现;相反,将ZIP注入海马体会损害物体位置任务的表现,但不会损害物体识别任务的表现。通过给予肽GluA2可以防止ZIP对物体识别的损害,GluA2可以阻断含GluA2的AMPA受体的内吞作用。最后,需要内嗅皮质功能的感知异常任务的表现不会被ZIP破坏。这些结果共同证明了类似LTP的机制对内嗅皮质中物体识别记忆维持的重要性。