Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice / 神经科学通报·英文版

Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.

Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy / 神经科学通报·英文版

Primary age-related tauopathy (PART) is characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. In the present study, we analyzed the distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART, Alzheimer's disease (AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages > 0 and ≤ IV, and a Thal phase of 0 (no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus, stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.

Clinical significance and surgical management strategy for colorectal high-grade intraepithelial neoplasia / 国际外科学杂志

Objective To analyze the clinical and pathological characteristics and its surgical management strategy for colorectal high-grade intraepithelial neoplasia (HGIN).Methods Eighty-two cases with colorectal tumors diagnosed as colorectal HGIN based on colonoscopic biopsy between January 2005 and December 2012 were enrolled in the study.The clinicopathological data of all the patients was collected and analyzed.Of the 82 cases,71 cases had radical colorectal surgery,1 cases had Miles operation after previous transanal excisions,3 had transanal local excisions,8 cases had palliative surgery.The surgical specimens were all examined pathologically and compared with the preoperative diagnosis of colonoscopic biopsy of all the patients.Results Three cases (3.7％) were pathologically diagnosed as high-grade intraepithelial neoplasia,their average diameter was 1.5 cm.The other 79 (96.3％) cases were diagnosed as adenocarcinoma,with an average diameter of 4.7 cm.The difference in tumor size was statistically significant (P ＜ 0.01).Comparison of pre-and post-operative specimens showed poor consistency,the Kappa value was O.104.Significant analysis showed a correlation between cancerous change to tumor size and depth of invasion.In the 79 cases confirmed as adenocarcinoma,liver metastasis occurred in 8 cases,regional lymph nodes metastasis in 31 cases (39.2％).Of the 33 cases with rectal tumors,30 cases (90.9％) were pathologically diagnosed as adenocarcinoma after operation.Conclusions Much attention should be payed to the pathological diagnosis in colorectal intraepithelial neoplasia,especially in the HGIN.We have found that of the cases first diagnosed as HGIN,approximately 96.3％ already have invasion adenocarcinoma.Most cases had reginonal lymph nodes metastasis.Liver metastasis had been occurred.thus active surgical measures should be taken.If the location of the tumor was not involved to anal sphincter,or cases with tumors larger than 3 cm was diagnosed,in highly suspected cases with malignant potiential,radical surgery is recommended.For tumors located at the lower rectum,the final decision should be made only after repeated endoscopic or transanal biopsy.