Cooper Tara L, Thompson John J, Turner Sean M, Watson Cory, Lubke Katelyn N, Logan Carly N, Maurer Andrew P, Burke Sara N
Department of Neuroscience, Evelyn F. McKnight Brain Institute, University of Florida, Gainesville, FL, United States.
Graduate Program in Biomedical Sciences, Neuroscience Concentration, University of Florida, Gainesville, FL, United States.
Front Syst Neurosci. 2022 Jun 30;16:920713. doi: 10.3389/fnsys.2022.920713. eCollection 2022.
It is well established that degradation of perforant path fibers is associated with age-related cognitive dysfunction and CA3 hyperactivity. Whether this fiber loss triggers a cascade of other functional changes within the hippocampus circuit has not been causatively established, however. Thus, the current study evaluated the effect of perforant path fiber loss on neuronal activity in CA3 and layer II of the lateral entorhinal cortex (LEC) in relation to mnemonic similarity task performance. Expression of the immediate early gene was quantified in rats that received a unilateral right hemisphere transection of the perforant path or sham surgery that cut the cortex but left the fibers intact. Behavior-related expression of mRNA was measured to test the hypothesis that fiber loss leads to elevated activation of CA3 and LEC neurons, as previously observed in aged rats that were impaired on the mnemonic similarity task. Transection of perforant path fibers, which has previously been shown to lead to a decline in mnemonic similarity task performance, did not alter expression. expression in CA3, however, was correlated with task performance on the more difficult discrimination trials across both surgical groups. These observations further support a link between CA3 activity and mnemonic similarity task performance but suggest the reduced input from the entorhinal cortex to the hippocampus, as observed in old age, does not causatively elevate CA3 activity.
众所周知，穿通通路纤维的退化与年龄相关的认知功能障碍和CA3过度活跃有关。然而，这种纤维损失是否会引发海马回路内一系列其他功能变化，尚未得到因果关系的确立。因此，当前的研究评估了穿通通路纤维损失对CA3和外侧内嗅皮质（LEC）II层神经元活动的影响，这与记忆相似性任务表现相关。在接受穿通通路单侧右半球横断或假手术（切断皮质但保留纤维完整）的大鼠中，对即刻早期基因的表达进行了定量。测量了与行为相关的mRNA表达，以检验纤维损失导致CA3和LEC神经元激活增加的假设，正如之前在记忆相似性任务受损的老年大鼠中观察到的那样。穿通通路纤维的横断，之前已证明会导致记忆相似性任务表现下降，但并未改变表达。然而，CA3中的表达与两个手术组在更困难的辨别试验中的任务表现相关。这些观察结果进一步支持了CA3活动与记忆相似性任务表现之间的联系，但表明如在老年时观察到的，内嗅皮质向海马的输入减少并不会因果性地提高CA3活动。
