Single-Unit Activity in the Medial Prefrontal Cortex during Immediate and Delayed Extinction of Fear in Rats

Delivering extinction trials minutes after fear conditioning yields only a short-term fear suppression that fully recovers the following day. Because extinction has been reported to increase CS-evoked spike firing and spontaneous bursting in the infralimbic (IL) division of the medial prefrontal cortex (mPFC), we explored the possibility that this immediate extinction deficit is related to altered mPFC function. Single-units were simultaneously recorded in rats from neurons in IL and the prelimbic (PrL) division of the mPFC during an extinction session conducted 10 minutes (immediate) or 24 hours (delayed) after auditory fear conditioning. In contrast to previous reports, IL neurons exhibited CS-evoked responses early in extinction training in both immediate and delayed conditions and these responses decreased in magnitude over the course of extinction training. During the retention test, CS-evoked firing in IL was significantly greater in animals that failed to acquire extinction. Spontaneous bursting during the extinction and test sessions was also different in the immediate and delayed groups. There were no group differences in PrL activity during extinction or retention testing. Alterations in both spontaneous and CS-evoked neuronal activity in the IL may contribute to the immediate extinction deficit

Coitus-Free Sexual Transmission of Zika Virus in a Mouse Model

Zika virus (ZIKV) is an arboviral infection that may be sexually transmitted. The present study aims to determine if accessory sex glands are a potential source of infectious virus and important in sexual transmission. Male interferon type I receptor knockout (Ifnar−/−) mice were challenged subcutaneously with a Puerto Rican ZIKV isolate. Reproductive tissues were harvested seven days after viral challenge and artificial insemination fluid derived from epididymis or homogenized accessory sex glands (seminal plasma) was obtained. Naïve interferon type I and II receptor knockout (AG129) females were pretreated with progesterone, and inoculated intravaginally with either epididymal flush or seminal plasma from ZIKV-infected males. ZIKV RNA was demonstrated in the artificial insemination fluid and ZIKV antigen was detected in epididymal epithelial cells but not within seminiferous tubules at the time of artificial insemination fluid collection. Peripheral viremia, demonstrated by ZIKV RNA in whole blood samples of females from each challenge group was observed. Infectious virus was present in both epididymal fluid and seminal plasma. These studies provide evidence of passage of virus from epididymal flush and seminal plasma to naïve females via artificial insemination and provides a model for the study of sexual transmission of ZIKV

Neuroendocrine - immune interactions in synovitis

Synovial tissue lines the noncartilaginous surfaces of synovial joints and supplies these avascular structures with nutrients. In diseases such as rheumatoid arthritis, inflammation of the synovial tissue - synovitis induces diffuse damage to the joints. The presence of functional receptors for glucocorticoids, androgens and estrogens in synoviocytes might link inflammation and the endocrine system at the local level. Synovial tissue could be regarded as an intracrine tissue, whereby active steroids influence the cells in which they are synthesized, without their release into the extracellular space. An increase in the peripheral metabolism of sex steroids is characteristic of rheumatoid synovitis, with an augmented ratio of estrogen to androgen occurring in both male and female patients. Changes in the peripheral nervous system at the site of local inflammation are also hallmarks of synovitis in rheumatoid arthritis. In the chronic phase of synovitis, sympathetic nerve fibers are lost; by contrast, sensory nerve fibers sprout into the inflamed tissue. Complex interactions occur between the endocrine, nervous and immune systems during synovitis. In particular, studying neuroendocrine - immune interactions in the inflamed synovium will potentially uncover new mechanisms in the pathophysiology of rheumatoid arthritis and might lead to new methods of therapeutic intervention