Cross-sectional and longitudinal studies in active duty and veteran cohorts have both demonstrated that deployment-acquired traumatic brain injury (TBI) is an independent risk factor for developing post-traumatic stress disorder (PTSD), beyond confounds such as combat exposure, physical injury, predeployment TBI, and pre-deployment psychiatric symptoms. This study investigated how resting-state brain networks differ between individuals who developed PTSD and those who did not following deployment-acquired TBI. Participants included postdeployment veterans with deployment-acquired TBI history both with and without current PTSD diagnosis. Graph metrics, including small-worldness, clustering coefficient, and modularity, were calculated from individually constructed whole-brain networks based on 5-min eyes-open resting-state magnetoencephalography (MEG) recordings. Analyses were adjusted for age and premorbid IQ. Results demonstrated that participants with current PTSD displayed higher levels of small-worldness, F(1,12) = 5.364, p < 0.039, partial eta squared = 0.309, and Cohen's d = 0.972, and clustering coefficient, F(1, 12) = 12.204, p < 0.004, partial eta squared = 0.504, and Cohen's d = 0.905, than participants without current PTSD. There were no between-group differences in modularity or the number of modules present. These findings are consistent with a hyperconnectivity hypothesis of the effect of TBI history on functional networks rather than a disconnection hypothesis, demonstrating increased levels of clustering coefficient rather than a decrease as might be expected; however, these results do not account for potential changes in brain structure. These results demonstrate the potential pathological sequelae of changes in functional brain networks following deployment-acquired TBI and represent potential neurobiological changes associated with deployment-acquired TBI that may increase the risk of subsequently developing PTSD.

Nicotine, the major psychoactive compound in tobacco, targets nicotinic acetylcholine receptors (nAChRs) and results in drug dependence. The nematode Caenorhabditis elegans’ (C. elegans) genome encodes conserved and extensive nicotinic receptor subunits, representing a useful system to investigate nicotine-induced nAChR expressions in the context of drug dependence. However, the in vivo expression pattern of nAChR genes under chronic nicotine exposure has not been fully investigated. To define the role of nAChR genes involved in nicotine-induced locomotion changes and the development of tolerance to these effects, we characterized the locomotion behavior combining the use of two systems: the Worm Tracker hardware and the WormLab software. Our results indicate that the combined system is an advantageous alternative to define drug-dependent locomotion behavior in C. elegans. Chronic (24-hour dosing) nicotine exposure at 6.17 and 61.7 μM induced nicotine-dependent behaviors, including drug stimulation, tolerance/adaption, and withdrawal responses. Specifically, the movement speed of naïve worms on nicotine-containing environments was significantly higher than on nicotine-free environments, suggesting locomotion stimulation by nicotine. In contrast, the 24-hour 6.17 μM nicotine-treated worms exhibited significantly higher speeds on nicotine-free plates than on nicotine-containing plates. Furthermore significantly increased locomotion behavior during nicotine cessation was observed in worms treated with a higher nicotine concentration of 61.7 μM. The relatively low locomotion speed of nicotine-treated worms on nicotine-containing environments also indicates adaption/tolerance of worms to nicotine following chronic nicotine exposure. In addition, this study provides useful information regarding the comprehensive in vivo expression profile of the 28 “core” nAChRs following different dosages of chronic nicotine treatments. Eleven genes (lev-1, acr-6, acr-7, acr-11, lev-8, acr-14, acr-16, acr-20, acr-21, ric-3, and unc-29) were significantly up-regulated following 61.7 μM nicotine treatment, in which worms showed significantly increased locomotion behavior. This study provides insights into the linkage between nicotine-induced locomotion behavior and the regulation of nicotinic acetylcholine receptors.

No abstract

Optogenetic proteins are powerful tools for advancing our understanding of neural circuitry. However, the precision of optogenetics is dependent in part on the extent to which expression is limited to cells of interest. The Thy1-ChR2 transgenic mouse is commonly used in optogenetic experiments. Although general expression patterns in these animals have been characterized, a detailed evaluation of cell-type specificity is lacking. This information is critical for interpretation of experimental results using these animals. We characterized ChR2 expression under the Thy1promoter in line 18 in comparison to known expression profiles of hippocampal cell types using immunohistochemistry in CA1. ChR2 expression did not colocalize with parvalbumin or calbindin expressing interneurons. However, we found ChR2 expression to be localized in the deep sublayer of CA1 in calbindin-negative pyramidal cells. These findings demonstrate the utility of the Thy1-ChR2-YFP mouse to study the activity and functional role of excitatory neurons located in the deep CA1 pyramidal cell layer.

To identify reliable reference genes for toxicological studies, 16 commonly-used reference genes were selected as candidates to evaluate their expression stabilities under experimental conditions in Caenorhabditis elegans. Sixteen candidates were composed of 12 protein-coding genes and 4 non-coding RNAs, they were act-2, ama-1, arp-6, cdc-42, csq-1, eif-3.C, idhg-1, mdh, pmp-3, rbd-1, tba-1, Y45F10D.4, 18S rRNA, Ce234, U18, and U6. Larval stage 1 synchronized hermaphrodites were exposed to benzo-α-pyrene (BαP), chlorpyrifos, diazinon, gossypol, zinc oxide nanoparticles, and the vehicle control DMSO for 30 h, respectively. Expression stabilities of candidate genes were analyzed using 4 independent evaluating approaches (BestKeeper, the delta Ct approach, geNorm, and NormFinder) followed by a comprehensive method. Results showed that there were slight differences in ranking order between evaluation methods due to their different assumptions and computations. The results also showed that responses of candidate genes to different chemicals were distinct, 18S rRNA was the best for BαP and chlorpyrifos, tba-1 was the most stable gene for diazinon and gossypol treatments, while pmp-3 was more stable for zinc oxide exposure. Additionally, results demonstrated that combinations of multiple genes were more reliable than individual gene, suggesting selecting two or more candidates as reference genes may generate more reliable results for toxicological studies.