Neuroscience
-
We here investigate the effects of two exercise modalities (endurance treadmill training-TM and voluntary free-wheel activity-FW) on the brain cortex and cerebellum mitochondrial bioenergetics, permeability transition pore (mPTP), oxidative stress, as well as on proteins involved in mitochondrial biogenesis, apoptosis, and quality control. Eighteen male rats were assigned to sedentary-SED, TM and FW groups. Behavioral alterations and ex vivo brain mitochondrial function endpoints were assessed. ⋯ Also, exercise increased the expression of proteins involved in mitochondrial biogenesis, autophagy and fusion, simultaneous with decreased expression of mitochondrial fission-related protein DRP1. In conclusion, physical exercise improves brain cortex and cerebellum mitochondrial function, decreasing oxidative stress and apoptotic related markers. It is also possible that favorable alterations in mitochondrial biogenesis, dynamics and autophagy signaling induced by exercise contributed to increased mitochondrial plasticity leading to a more robust phenotype.
-
Opioid-induced rewarding and motorstimulant effects are mediated by an increased activity of the ventral tegmental area (VTA) dopamine (DA) neurons. The excitatory mechanism of opioids on VTA-DA neurons has been proposed to be due to the depression of GABAergic synaptic transmission in VTA-DA neurons. ⋯ Our results showed that (1) DAMGO inhibits GABAergic inputs in VTA-DA neurons at presynaptic sites; (2) effect of DAMGO on GABAergic inputs in VTA-DA neurons is inhibited by potassium channel blocker 4-aminopyridine (4-AP) and Gi protein inhibitor N-ethylmaleimide (NEM); (3) phospholipase A2 (PLA2) does not mediate the effect of DAMGO on GABAergic inputs in VTA-DA neurons, but mediates it in the periaqueductal gray (PAG); (4) multiple downstream signaling molecules of μ receptors do not mediate the effect of DAMGO on GABAergic inputs in VTA-DA neurons. These results suggest that DAMGO depresses inhibitory synaptic transmission via μ receptor-Gi protein-Kv channel pathway in VTA-DA neurons, but via μ receptor-PLA2 pathway in PAG neurons.
-
Addiction is a chronic relapsing disorder characterized by the loss of control over drug intake, high motivation to obtain the drug, and a persistent craving for the drug. Accumulating evidence implicates cellular and molecular alterations within cortico-basal ganglia-thalamic circuitry in the development and persistence of this disease. ⋯ Here, we review the use of new technologies, including optogenetics and DREADDs (Designer Receptors Exclusively Activated by Designer Drugs), in unraveling the role of the striatum in addiction. In particular, we focus on the role of striatal cell populations (i.e., direct and indirect pathway medium spiny neurons) and striatal dopaminergic and glutamatergic afferents in addiction-related plasticity and behaviors.
-
The concept of synergy provides a theoretical framework for movement stability resulting from the neural organization of multiple elements (digits, muscles, etc.) that all contribute to salient performance variables. Although stability of performance is obviously important for steady-state tasks leading to high synergy indices, a feed-forward drop in synergy indices is seen in preparation to a quick action (i.e., anticipatory synergy adjustments, ASAs). ⋯ Taken together, these results point at subcortical structures that are crucial for proper control of movement stability. It is timely to introduce the concept of impaired control of stability as an objective, quantifiable, and theory-based clinical descriptor of movement disorders that can increase our understanding of the neural control of movement with all of its implications for clinical practice.
-
Stimuli paired with rewards acquire reinforcing properties to promote reward-seeking behavior. Previous work supports the role of ventral tegmental area (VTA) nicotinic acetylcholine receptors (nAChRs) in mediating conditioned reinforcement elicited by drug-associated cues. However, it is not known whether these cholinergic mechanisms are specific to drug-associated cues or whether VTA cholinergic mechanisms also underlie the ability of cues paired with natural rewards to act as conditioned reinforcers. ⋯ AP-5 robustly attenuated conditioned reinforcement and blocked discrimination between CR and NCR noseports at the 1-μg dose. MEC infusion decreased responding for both CR and NCR while 66.7-μg SCOP disrupted the subject's ability to discriminate between CR and NCR. Together, our data suggest that VTA NMDARs and mAChRs, but not nAChRs, play a role in the ability of natural reward-associated cues to act as conditioned reinforcers.