Lateral septum inputs to nucleus accumbens mediates stress induced suppression of natural reward seeking.

Stress alters the level of reward evaluation and seeking. However, the neural circuitry mechanisms underlying stress induced effects on natural reward seeking remain unclear. Here we report a septal-accumbens pathway that mediates the effects of acute stress on reward seeking suppression. We first established the sucrose oral self-administration paradigm and measured the effects of acute stress on reward seeking behavior after 21 days of abstinence. Both forced swimming stress and foot shock stress significantly suppressed the natural reward seeking. Among a variety of brain regions, intermediolateral septum (LSi) appear as a strong stress-responsive area containing abundant c-Fos positive cells; chemogenetic inactivation of LSi reinstated the reward seeking behavior. To elucidate the downstream targets receiving LSi projections, we combined pathway-specific retro-labeling and chemogenetic manipulation to confirm the involvement of LSi-nucleus accumbens (NAc) rather than the Ventral tegmental area (VTA) in mediating the observed behavioral responses. In conclusion, the septal-accumbal projection constitute a discrete circuit dictating the stress evoked alterations on reward seeking and may implicate in treatment of stress induced anhedonia.

Dynamic Changes of Arc Expression in Dorsal Striatum of Mice After Self-Administration of Sucrose.

Region-specific plasticity in the striatal circuit plays an important role in the development and long-term maintenance of skills and sequential movement procedures. Studies investigating the molecular substrates that contribute to the plasticity changes during motor skill processes have documented a transition in expression from the dorsomedial striatum (DMS) to the dorsolateral striatum (DLS); however, few studies have explored the expression pattern of molecular substrates in the dorsal striatum during progression of instrumental learning. To address this issue, the activity-regulated cytoskeleton-associated protein (Arc) expressions in the subregional dorsal striatum were analyzed during the early and late learning phases of the 10-day sucrose self-administration process. We found that Arc protein is primarily detected in the DMS only in the initial learning stage; however, it is expressed in the DLS during both early and late learning stages. Moreover, Arc expression in the DMS correlated with the number of rewards received later in the training. These data indicated that the Arc expression in subregions of the dorsal striatum shows region-specific transfer and that Arc expression in the DMS contributes to obtaining reward in later learning stage during the process of instrumental learning.

Changes of histopathology and molecular indicators in breast cancer after neoadjuvant chemotherapy / 临床与实验病理学杂志

Purpose To observe the changes of histopathology and expression levels of ER, PR, HER-2 and Ki-67 in breast cancer after neoadjuvant chemotherapy (NTC), and to evaluate the relationship between the curative effect and clinico-pathological characteristics of breast cancer. Methods 93 ca-ses of invasive breast cancer with NTC were collected and retro-spectively analyzed. Pathologic evaluation of chemotherapeutic effect were evaluated by Miller-Payne (MP) grading system. Results Tumor cells, tumor stroma and lymph nodes status presented different histopathological changes after NTC. There were significant relationship between curative effect and patients age (Z=-1.993, P=0.046 ), histological grade (χ2=7.261, P=0.027), molecular subtypes (χ2=8.289, P=0.040), while it had no statistical relationship between curative effect and tumor size (Z=-1.091, P=0.275) and lymph node status (Z=-1.107, P = 0.268). Expression of ER, PR, HER-2 and Ki-67 showed different degrees of change before and after NTC. The concordance rates of ER, PR, HER-2 and Ki-67 were 81.0％, 72.2％, 83.5％ and 55.7％, respective-ly. And there was no significant difference in expression of these four molecular indicators before and after NTC (χ2 =0.428, P=0.934). Conclusion The histomorphology of tumor cell, tumor stroma and lymph node status can be influenced by NTC. Objective evaluation of the changes of histopathology and molecular indicators after NTC may valuable in predicting clinical prognosis and guiding individual treatment of breast cancer.