Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions

Altered Perceptual Sensitivity to Kinematic Invariants in Parkinson's Disease

Ample evidence exists for coupling between action and perception in neurologically healthy individuals, yet the precise nature of the internal representations shared between these domains remains unclear. One experimentally derived view is that the invariant properties and constraints characterizing movement generation are also manifested during motion perception. One prominent motor invariant is the “two-third power law,” describing the strong relation between the kinematics of motion and the geometrical features of the path followed by the hand during planar drawing movements. The two-thirds power law not only characterizes various movement generation tasks but also seems to constrain visual perception of motion. The present study aimed to assess whether motor invariants, such as the two thirds power law also constrain motion perception in patients with Parkinson's disease (PD). Patients with PD and age-matched controls were asked to observe the movement of a light spot rotating on an elliptical path and to modify its velocity until it appeared to move most uniformly. As in previous reports controls tended to choose those movements close to obeying the two-thirds power law as most uniform. Patients with PD displayed a more variable behavior, choosing on average, movements closer but not equal to a constant velocity. Our results thus demonstrate impairments in how the two-thirds power law constrains motion perception in patients with PD, where this relationship between velocity and curvature appears to be preserved but scaled down. Recent hypotheses on the role of the basal ganglia in motor timing may explain these irregularities. Alternatively, these impairments in perception of movement may reflect similar deficits in motor production

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion