Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by ...dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect-pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine’s ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response.
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•Synchronized activation of GABA transmission from multiple iMSNs inhibits APs in dMSNs•Cocaine suppresses lateral inhibition via D2Rs in iMSNs to disinhibit dMSNs•D2R agonist show higher efficacy at axon collaterals than at projections to VP•D2Rs in iMSNs are required for the stimulant effect of cocaine on locomotion
Dobbs et al. uncover a novel synaptic mechanism by which cocaine exerts its stimulant effect on locomotion. They show that cocaine suppresses the lateral inhibition between neurons in the nucleus accumbens to disinhibit striatal neurons and promote locomotion.
•We disaggregate adaptive capacity into specific and generic elements.•Our heuristic evaluates the interaction of generic and specific adaptive capacities.•Empirical cases show potential tradeoffs ...among capacities across decision levels.•Institutions and policy mediate tradeoffs and may lead to maladaptive outcomes.•Evaluation of distinct capacities can improve development and adaptation synergies.
There are two forms of capacity to adapt to global change: those associated with fundamental human development goals (generic capacity), and those necessary for managing and reducing specific climatic threats (specific). We argue that these two domains of capacity must be addressed explicitly, simultaneously and iteratively if climate change adaptation and sustainable development goals are to be attained. We propose a simple heuristic to understand the four main ways these two capacities interact, leading to more or less desirable outcomes. Drawing from three case studies of agricultural adaptation to climatic risk (Phoenix, AZ; Northeast Brazil; Chiapas, Mexico) we argue that the institutional context of adaptation can implicitly or explicitly undermine one form of capacity with repercussions for the development of the other. A better and more strategic balance of generic and specific capacities is needed if the promised synergies between sustainable development and adaptation are to be achieved.
The increase in global biodiesel production makes imperative the development of sustainable processes for the use of its main by-product, crude glycerol. In this study the feasibility of ...polyhydroxyalkanoates (PHA) production by a mixed microbial community using crude glycerol as feedstock was investigated. The selected culture had the ability to consume both glycerol and methanol fraction present in the crude. However, glycerol seemed to be the only carbon source contributing for the two biopolymers stored: poly-3-hydroxybutyrate (PHB) and glucose biopolymer (GB). In this work the culture reached a maximum PHB content of 47% (cdw) and a productivity of 0.27 g X/L.d, with an aerobic mixed cultures and a real waste substrate with non-volatile fatty acids (VFA) organic matter. The overall PHA yield on total substrate obtained was in the middle range of those reported in literature. The fact that crude glycerol can be used to produce PHA without any pre-treatment step, makes the overall production process economically more competitive, reducing polymer final cost.
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•Crude glycerol was used as feedstock to produce biopolymers using aerobic mixed cultures.•From the glycerol fraction of the crude PHB and GB were stored.•A maximum PHB content of 47% cell dry cell was obtain with crude glycerol.•Selected culture was able to achieve 53% of PHB using synthetic glycerol.
Bradykinesia is a prominent phenotype of Parkinson’s disease, depression, and other neurological conditions. Disruption of dopamine (DA) transmission plays an important role, but progress in ...understanding the exact mechanisms driving slowness of movement has been impeded due to the heterogeneity of DA receptor distribution on multiple cell types within the striatum. Here we show that selective deletion of DA D2 receptors (D2Rs) from indirect-pathway medium spiny neurons (iMSNs) is sufficient to impair locomotor activity, phenocopying DA depletion models of Parkinson’s disease, despite this mouse model having intact DA transmission. There was a robust enhancement of GABAergic transmission and a reduction of in vivo firing in striatal and pallidal neurons. Mimicking D2R signaling in iMSNs with Gi-DREADDs restored the level of tonic GABAergic transmission and rescued the motor deficit. These findings indicate that DA, through D2R activation in iMSNs, regulates motor output by constraining the strength of GABAergic transmission.
•D2R deletion from indirect-pathway medium spiny neurons (iMSNs) causes bradykinesia•In contrast to predictions, firing of iMSNs was reduced in this mouse model•Loss of striatal D2Rs robustly increased GABA transmission in the basal ganglia•Gi-DREADD activation in iMSNs restored GABA tone and locomotion
Lemos et al. find that targeted deletion of dopamine D2 receptors from indirect-pathway medium spiny neurons (iMSNs) leads to enhanced GABAergic transmission downstream of iMSNs. This enhanced GABAergic tone causes a Parkinsonian-like motor deficit similar to dopamine depletion models.
Abstract The aim of this systematic review and meta-analysis was to compare the survival rate of the implants and the peri-implant tissue changes associated with implants inserted in fresh extraction ...sockets and those inserted in healed sockets. This review has been registered at PROSPERO under the number CRD42016043309. A systematic search was conducted by two reviewers independently in the databases PubMed/MEDLINE, Embase, and the Cochrane Library using different search terms; articles published until November 2016 were searched for. The searches identified 30 eligible studies. A total of 3,049 implants were installed in a total of 1,435 patients with a mean age of 46.68 years and a minimum of 6 months of follow-up. The survival rate of delayed implants (98.38%) was significantly greater than immediate implants (95.21%) ( p = .001). For the marginal bone loss ( p = .32), implant stability quotients values ( p = .44), and pocket probing depth ( p = .94) there was no significant difference between the analysed groups. The immediate implants placed in fresh sockets should be performed with caution because of the significantly lower survival rates than delayed implants inserted in healed sockets.
The radiation produced when an intense laser interacts with a solid target could provide a cheaper source of X-rays to synchrotrons and free-electron lasers. But they can also produce short bursts of ...gamma rays, whereas synchrotrons do not.
Stress is a complex human experience and having both rewarding and aversive motivational properties. The adverse effects of stress are well documented, yet many of underlying mechanisms remain ...unclear and controversial. Here we report that the anxiogenic properties of stress are encoded by the endogenous opioid peptide dynorphin acting in the basolateral amygdala. Using pharmacological and genetic approaches, we found that the anxiogenic-like effects of Corticotropin Releasing Factor (CRF) were triggered by CRF(1)-R activation of the dynorphin/kappa opioid receptor (KOR) system. Central CRF administration significantly reduced the percent open-arm time in the elevated plus maze (EPM). The reduction in open-arm time was blocked by pretreatment with the KOR antagonist norbinaltorphimine (norBNI), and was not evident in mice lacking the endogenous KOR ligand dynorphin. The CRF(1)-R agonist stressin 1 also significantly reduced open-arm time in the EPM, and this decrease was blocked by norBNI. In contrast, the selective CRF(2)-R agonist urocortin III did not affect open arm time, and mice lacking CRF(2)-R still showed an increase in anxiety-like behavior in response to CRF injection. However, CRF(2)-R knockout animals did not develop CRF conditioned place aversion, suggesting that CRF(1)-R activation may mediate anxiety and CRF(2)-R may encode aversion. Using a phosphoselective antibody (KORp) to identify sites of dynorphin action, we found that CRF increased KORp-immunoreactivity in the basolateral amygdala (BLA) of wildtype, but not in mice pretreated with the selective CRF(1)-R antagonist, antalarmin. Consistent with the concept that acute stress or CRF injection-induced anxiety was mediated by dynorphin release in the BLA, local injection of norBNI blocked the stress or CRF-induced increase in anxiety-like behavior; whereas norBNI injection in a nearby thalamic nucleus did not. The intersection of stress-induced CRF and the dynorphin/KOR system in the BLA was surprising, and these results suggest that CRF and dynorphin/KOR systems may coordinate stress-induced anxiety behaviors and aversive behaviors via different mechanisms.
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•The main non-genomic vascular mechanism of Testosterone (T) is vasorelaxation.•T causes dependent-endothelium vasodilation by Gi/o protein and PKA activation.•T causes ...independent-endothelium vasodilation by pGC and PKG activation.•T-induced PKG activation activate Kv and BKCa and inactivate L-Type VOCC channels.•T is beneficial to the cardiovascular system and TRT may become a CVD treatment.
Testosterone (T) is the predominant endogenous androgen in the bloodstream. At the vascular level, T presents genomic and non-genomic effects, and both effects may overlap. The genomic actions assume that androgens can freely cross the plasma membrane of target cells and bind to nuclear androgen receptors, inducing gene transcription and protein synthesis. The non-genomic effects have a more rapid onset and may be related to the interaction with protein/receptor/ion channels of the plasma membrane. The key T effect at the vascular level is vasorelaxation, which is primarily due to its rapid effect. Thus, the main purpose of this review is to discuss the T non-genomic effects at the vascular level and the molecular pathways involved in its vasodilator effect observed in in vivo and in vitro studies. In this sense, the nuclear receptor activation, the influence of vascular endothelium and the activation or inhibition of ion channels (potassium and calcium channels, respectively) will be reviewed regarding all the data that corroborated or not. Moreover, this review also provides a brief update on the association of T with the risk factors for cardiovascular diseases, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia, and hypertension. In summary, in this paper we consider the non-genomic vascular mode of action of androgen in physiological conditions and the main risk factors for cardiovascular diseases.
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