Behavioral Effects of Acute Systemic Low-Dose Clozapine in Wild-Type Rats: Implications for the Use of DREADDs in Behavioral Neuroscience

Designer receptors exclusively activated by designer drugs (DREADDs) are popular tools used to manipulate the activity of defined groups of neurons. Recent work has shown that DREADD effects in the brain are most likely not mediated by the proposed ligand clozapine-N-oxide (CNO) but its metabolite clozapine (CLOZ). However, it is not known whether low doses of CLOZ required to activate DREADDs already have DREADD-independent effects on behavior as described for higher CLOZ doses used in previous preclinical studies. To close this gap, we compared effects of acute systemic (i.p.) CLOZ treatment vs. vehicle (VEH) in a wide range of behavioral tests in male wild-type rats. We found that CLOZ doses as low as 0.05–0.1 mg/kg significantly affected locomotion, anxiety and cognitive flexibility but had no effect on working memory or social interaction. These results highlight the need for careful controls in future chemogenetic experiments and show that previous results in studies lacking CNO/CLOZ controls may require critical re-evaluation

Overview of core impurity transport in the first divertor operation of Wendelstein 7-X

The impurity transport at Wendelstein 7-X during its most recent campaign is characterized and documented for a variety of different plasma scenarios. An overview of its dependence on several quantities is given, which allows identification of transport regimes and the major driver for impurity transport. Beyond this, a comparison with the impurity behavior in other fusion devices is now possible. In contrast to other stellarators, no density dependence of the impurity transport has been found. Additionally, the influence of the turbulence contribution to the overall transport is reflected in the dependence on various parameters, e.g. turbulent diffusion and density fluctuation amplitudes. With this database approach, one can now also apply scaling laws to make extrapolations about the impurity confinement in future plasma scenarios

Species-conserved mechanisms of cognitive flexibility in complex environments

Flexible decision making in complex environments is a hallmark of intelligent behavior but the underlying learning mechanisms and neural computations remain elusive. Through a combination of behavioral, computational and electrophysiological analysis of a novel multidimensional rule-learning paradigm, we show that both rats and humans sequentially probe different behavioral strategies to infer the task rule, rather than learning all possible mappings between environmental cues and actions as current theoretical formulations suppose. This species-conserved process reduces task dimensionality and explains both observed sudden behavioral transitions and positive transfer effects. Behavioral strategies are represented by rat prefrontal activity and strategy-related variables can be decoded from magnetoencephalography signals in human prefrontal cortex. These mechanistic findings provide a foundation for the translational investigation of impaired cognitive flexibility.One-Sentence SummaryBoth rats and humans use behavioral strategies to infer task rules during multidimensional rule-learning

Quantitative comparison of impurity transport in turbulence reduced and enhanced scenarios at Wendelstein 7-X

We assess the turbulent particle transport being responsible for the limitation of the confinement and, thus, the overall performance of the neoclassically optimized stellarator Wendelstein 7-X. The radial particle transport is experimentally inferred from the evaluation of impurity injection into turbulence reduced and enhanced plasma scenarios revealing a completely different confinement behavior. The impact of the density gradient on the turbulent ion transport is theoretically estimated using large-scale non-linear gyro-kinetic simulations enabling, for the first time in Wendelstein 7-X, a quantitative comparison to the experimentally assessed impurity transport properties. We demonstrate that impurity transport in most of the Wendelstein 7-X discharges, up to now impossible to cover only with neoclassical estimations, is dominated by turbulence and can be modelled via gyro-kinetic simulations