Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ 07103, USA; Department of Molecular, Cell and Systems Biology, University of California Riverside, Riverside, CA 92521, USA.
Department of Molecular, Cell and Systems Biology, University of California Riverside, Riverside, CA 92521, USA.
Exp Neurol. 2023 Dec;370:114578. doi: 10.1016/j.expneurol.2023.114578. Epub 2023 Oct 18.
Traumatic brain injury leads to cellular and circuit changes in the dentate gyrus, a gateway to hippocampal information processing. Intrinsic granule cell firing properties and strong feedback inhibition in the dentate are proposed as critical to its ability to generate unique representation of similar inputs by a process known as pattern separation. Here we evaluate the impact of brain injury on cellular decorrelation of temporally patterned inputs in slices and behavioral discrimination of spatial locations in vivo one week after concussive lateral fluid percussion injury (FPI) in mice. Despite posttraumatic increases in perforant path evoked excitatory drive to granule cells and enhanced ΔFosB labeling, indicating sustained increase in excitability, the reliability of granule cell spiking was not compromised after FPI. Although granule cells continued to effectively decorrelate output spike trains recorded in response to similar temporally patterned input sets after FPI, their ability to decorrelate highly similar input patterns was reduced. In parallel, encoding of similar spatial locations in a novel object location task that involves the dentate inhibitory circuits was impaired one week after FPI. Injury induced changes in pattern separation were accompanied by loss of somatostatin expressing inhibitory neurons in the hilus. Together, these data suggest that the early posttraumatic changes in the dentate circuit undermine dentate circuit decorrelation of temporal input patterns as well as behavioral discrimination of similar spatial locations, both of which could contribute to deficits in episodic memory.
创伤性脑损伤导致齿状回的细胞和回路变化，这是海马信息处理的门户。内在颗粒细胞放电特性和齿状回中的强反馈抑制被认为是其通过称为模式分离的过程生成相似输入的独特表示的关键。在这里，我们评估了脑损伤对细胞去相关的影响暂时模式化输入在切片和行为辨别空间位置体内一周后，在小鼠的震荡性侧液击伤（FPI）后。尽管创伤后增加了传入路径对颗粒细胞的兴奋性驱动和增强的 ΔFosB 标记，表明兴奋性持续增加，但 FPI 后颗粒细胞的尖峰可靠性并未受损。尽管颗粒细胞在 FPI 后仍能有效地去相关记录到的相似时间模式输入集的输出尖峰序列，但它们去相关高度相似输入模式的能力却降低了。与此同时，在涉及齿状回抑制回路的新物体位置任务中，对相似空间位置的编码能力在 FPI 后一周受损。模式分离的损伤诱导变化伴随着门区中生长抑素表达抑制神经元的丧失。综上所述，这些数据表明，创伤后早期齿状回回路的变化破坏了齿状回对时间输入模式的去相关，以及对相似空间位置的行为辨别，这两者都可能导致情景记忆缺陷。
