Objective:To analyze the differences in neuronal activation during fear memory extinction in various sub-regions of the hippocampus in post-traumatic stress disorder(PTSD)mice.Methods:Two immediate early gene-pro-tein labeling strategies were employed to label neurons associated with fear extinction in PTSD mice.In the first group,Arc protein in hippocampal neurons was labeled and observed through immunofluorescence staining in wild-type mice.In the second group,Fos-CreERT2;Ai9 transgenic mice were injected with tamoxifen 23 hours prior to inducing fear memory extinction,and the relevant neurons were labeled with fluorescent proteins for observation.The number of labeled hippocampal neurons and the dendritic branch structure were analyzed to compare the activation levels of hipp-ocampal neurons and the plasticity of neuronal dendrites.Results:The two groups of Arc and Fos positive neurons were mainly distributed in the dorsal hippocampus,in which Arc protein chromogenic was enriched in CA3 and DG subre-gions,while CA1 and CA2 subregions were scattered,while Fos-positive neurons were enriched in the DG subregion of hippocampus and scattered in CA1,CA2 and CA3 subregions.Compared to the control group,there was no significant difference in the number of neurons expressing Arc protein in each subregion of the hippocampus in the PTSD group.The number of Fos-positive neurons in CA1,CA3 and DG subregions in the hippocampus of the PTSD group was signifi-cantly increased(P＜0.01).The dendritic branches of neurons in the hippocampal region were observed and analyzed in Fos-CreERT2;Ai9 mice from both groups,but no significant changes were found.Conclusion:Abnormal activation of neurons occurs in different subregions of the hippocampus during fear extinction in PTSD mice,although there are no significant plasticity changes in the dendritic branches of the activated neurons.

Objective : To study the effect of leucine rich repeat kinase 2 ( LRRK2) on pain sensitivity in neuro- pathic pain (NP) rats and explore its possible mechanism． Methods : 48 SD rats were randomly divided into four groups : sham surgery (Sham) ，model，LRRK2 inhibitor(MLi-2) ，and LRRK2 inhibitor + p38 mitogen activated pro- tein kinase (MAPK) agonist (MLi-2 + Anisomycin) ，with 12 rats in each group．The NP rat model was induced by chronic constriction injury ( CCI) of the sciatic nerve．Intrathecal injection of MLi-2 ( 1 mg / kg，10 μl) or Anisomy- cin (20 μmol / L，10 μl) was started from the 8 th day after surgery，once a day for 7 consecutive days．Pain sensi- tivity tests were conducted before surgery (day 0) and on postoperative days 7 and 14，respectively．The changes in mechanical withdrawal threshold (MWT) and paw withdraw thermal latency (PWTL) were analyzed in each group of rats．ELISA was used to detect the levels of interleukin-1 β (IL-1 β) ，IL-6 and tumor necrosis factor-α (TNF-α) in the dorsal horn of the rat spinal cord．Nissl staining was used to observe the pathological changes of neurons in rat spinal cord tissue．Immunofluorescence staining was used to observe the expression levels of ionized calcium-binding adapter molecule-1 (Iba-1) ，a marker of microglia in the spinal cord of rats ．Western blot was used to detect theprotein expression levels of LRRK2，p-p38 mitogen activated protein kinase (MAPK) ，p38 MAPK，and Iba-1 in the dorsal horn of the rat spinal cord. Results : Compared with the sham group，the model group showed a significant decrease in MWT and PWTL in the right hind limb of rats (P＜0. 01) ．The levels of IL-1，IL-6，and TNF in the spi- nal dorsal horn tissue，as well as the expression levels of LRRK2，Iba-1 proteins and p-p38 MAPK / p38 MAPK pro- tein ratio significantly increased (P＜0. 01) ．The proportion of Iba-1 positive cells in the spinal cord tissue signifi- cantly increased (P＜0. 01) ，while Nissl bodies were significantly reduced (P＜0. 01) ．Compared with the model group，the MLi-2 group showed a significant increase in MWT and PWTL in the right hind limb of rats (P＜0. 01) ， a significant increase in Nissl bodies (P＜0. 01) ，a significant decrease in the proportion of Iba-1 positive cells in the spinal cord tissue (P＜0. 01) ，and a significant decrease in the levels of IL-1，IL-6，and TNF and the expression levels of LRRK2，Iba-1 proteins and p-p38 MAPK / p38 MAPK protein ratio (P＜0. 01) ．However，Anisomychin in- tervention could activate the p38 MAPK signaling pathway and partially reverse the beneficial effects of MLi-2 on pain sensitivity and neuroinflammation in rats with neuropathic pain． Conclusion Inhibiting the expression of LRRK2 can alleviate pain sensitivity in NP rats induced by microglia activation mediated neuroinflammation，and its mechanism of action may be related to regulating the p38 MAPK signaling pathway.