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A Subset of VTA DA Neurons Demonstrates High Sensitivity to Acute Ethanol and Enhanced Sensitivity after Adolescent Drinking
Ethanol (EtOH) is a commonly used drug which exerts many of its effects by altering neurotransmission in the mesolimbic dopamine (DA) system. Although there is little debate that EtOH acts to increase the activity of DA neurons in the ventral tegmental area (VTA), and that this action is necessary for some of the reinforcing effects of EtOH, research in vitro has only been able to demonstrate an excitatory effect on VTA DA neurons in response to very high concentrations of EtOH. These concentrations, typically in the range of 50-100 mM, correspond to sedative or lethal levels for typical humans. Therefore, the significance of findings from in vitro experiments can be difficult to interpret. We sought to determine why high concentrations of EtOH are needed in vitro and whether this could be explained by simple experimental factors, including cytosolic washout from whole cell electrophysiological recordings; heterogeneity among VTA DA neurons, where previous studies may have inadvertently focused on an EtOH-insensitive population; or selection of animal population, where perhaps low EtOH response is characteristic in naïve, rather than EtOH-experienced, animals. To achieve this, we performed cell-attached recordings on a large number of midbrain DA neurons of EtOH-naïve and experienced mice.
We report evidence for a highly EtOH-responsive, medially located population of VTA DA neurons. These neurons, found within the rostral linear and interfascicular nuclei and considered “atypical” in terms of physiological criteria ascribed to DA neurons, exhibited a concentration-dependent increase of firing activity in response to EtOH, with some neurons responsive to as little as 20 mM EtOH. In contrast, DA neurons in the lateral VTA and substantia nigra were either unresponsive or responded only to 100 mM EtOH.
We then examined neuronal activity following adolescent binge-like alcohol drinking in mice, to determine whether EtOH experience drives increased EtOH sensitivity of DA neurons. We find that in medial VTA DA neurons, drinking experience greatly increased firing activity driven by subsequent exposure to EtOH itself, without altering other measures of intrinsic excitability. This enhanced sensitivity was no longer significant in the presence of glutamate receptor blockade. We attempted to further characterize the EtOH-sensitive, medially located VTA DA neurons by utilizing retrograde tracing to identify a population of nucleus accumbens medial shell-projecting neurons. We find that this population exhibits an increased sensitivity to 50 mM EtOH after adolescent drinking.
As a result of these experiments, we have identified a previously uncharacterized, highly EtOH-responsive population of DA neurons in the medial VTA. This population demonstrates an excitatory response to 10 and 20 mM EtOH, concentrations which are more pharmacologically relevant than those typically tested in vitro. We further demonstrate evidence for experience-induced neural adaptations which result in enhanced sensitivity to EtOH in vitro. These adaptations are only apparent in medial VTA DA neurons, and this phenomenon only occurs in response to adolescent drinking. These data provide evidence for a novel form of plasticity in which neurons respond to a primary reinforcer, in this case EtOH, after drinking experience. These findings provide an anatomical and pharmacological distinction between DA neuron subpopulations that will facilitate future mechanistic studies on the actions of EtOH in the VTA
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Dealing with the difficult student in emergency medicine
Dealing with a student who is perceived as difficult to work with or teach is inevitable in any academic physician's career. This paper will outline the basic categories of these difficulties pertinent to Emergency Medicine rotations in order to facilitate appropriate identification of problems. Strategies for evaluation and reporting of the difficult student are presented. Remediation, based on the type of difficulty, is addressed. Timeliness of reporting, evaluation, and feedback are invaluable to allow for appropriate assessment of the outcome of the remediation plan
Prevalencia de trastornos temporomandibulares en pacientes total y parcialmente edéntulos de la clínica UCSG- A 2017
Se realizó un estudio de tipo clínico, transversal, analítico y correlacional en adultos total y parcialmente edentulos de 30 a 80 años de edad. Objetivo: determinar la prevalencia de trastornos temporomandibulares en pacientes total y parcialmente edéntulos del grupo de estudio. Metodología: la recolección de datos se realizó mediante una encuesta a todos los pacientes participantes de la investigación. Los signos y síntomas que se evaluaron fueron: dolor a la apertura y cierre mandibular, clic, crepitación, dolor a la palpación, dolor de la articulación temporomaxilar ausencia dentaria, dimensión vertical y tipo rehabilitación protésica existente. El examen clínico se realizó en la clínica odontológica de la UCSG donde se realizó las valoraciones de los signos y síntomas antes descritos. Resultados: El 66,67% de los pacientes presentó por lo menos un síntoma de trastornos temporomandibular. Los signos más frecuentes fueron los ruidos articulares, que se presentó en el 50% de los pacientes parcialmente edéntulos y el 10% en los pacientes totalmente edentulos. También se encontró un valor significativo de p=0.03 en relación al edentulismo total o parcial con relación al dolor de la ATM, lo que determina que existe una relación significativa entre edentulismo total-parcial y el dolor a la articulación termporomandibular
Loss of Striatonigral GABAergic Presynaptic Inhibition Enables Motor Sensitization in Parkinsonian Mice
SummaryDegeneration of dopamine (DA) neurons in Parkinson’s disease (PD) causes hypokinesia, but DA replacement therapy can elicit exaggerated voluntary and involuntary behaviors that have been attributed to enhanced DA receptor sensitivity in striatal projection neurons. Here we reveal that in hemiparkinsonian mice, striatal D1 receptor-expressing medium spiny neurons (MSNs) directly projecting to the substantia nigra reticulata (SNr) lose tonic presynaptic inhibition by GABAB receptors. The absence of presynaptic GABAB response potentiates evoked GABA release from MSN efferents to the SNr and drives motor sensitization. This alternative mechanism of sensitization suggests a synaptic target for PD pharmacotherapy
Análisis del benchmarking como herramienta de apoyo para la toma de decisiones de las empresas
En el presente artículo se expone el benchmarking como una herramienta de apoyo para la toma de decisiones, para realizar el análisis correspondiente se utilizaron datos obtenidos de libros, y ejemplares facilitados por instituciones que utilizaron el benchmarking. El método aplicado para este estudio fue el método inductivo, los resultados que obtuvimos nos demostraron que el benchmarking proporciona grandes beneficios para las entidades en general y permite un desarrollo adecuado del proceso de toma de decisiones, en conclusión el benchmarking es una herramienta muy eficiente para la toma de decisiones
Alcohol Binge Drinking:Negative and Positive Valence System Abnormalities
This work was supported by an award from Dundee University Medical School (ref. AT27) to ST and JDS. Spectroscopy was supported by an unrestricted ‘Work in Progress’ agreement with Siemens.Background: Three million deaths occur each year due to alcohol misuse. Translational studies are crucial to translate preclinical findings to patients. Preclinical studies have highlighted abnormalities in specific brain systems with these forming the basis of allostasis theory. However, few studies have tested predictions in humans using neuroimaging. Methods: Here we used a Research Domain Criteria (RDoC) approach to testallostasis theory predictions of blunted positive valence system (PVS) and abnormally increased negative valence system (NVS) responses in fifty-seven binge alcohol drinking subjects and healthy controls who completed an instrumental task during fMRI. Results: As hypothesised, binge alcohol drinkers showed abnormally increased activity in NVS-linked regions such as the hippocampus and dorsal cingulate, and abnormally blunted activity in PVS-linked regions such as the striatum, compared to controls. Higher measures of problematic alcohol use were associated with more abnormal brain activity, only for binge drinkers who had been most recently drinking. Conclusions: These results support allostasis theory predictions of abnormally increased NVS and blunted PVS responses in binge alcohol drinkers. Further similar translational neuroimaging studies are indicated, particularly focusing on the NVSPostprintPeer reviewe
Cellular, circuit and transcriptional framework for modulation of itch in the central amygdala
Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of the cells and neural circuits that organize this information remains elusive. Here, we show the necessity and sufficiency of chloroquine-activated neurons in the central amygdala (CeA) for both itch sensation and associated aversion. Further, we show that chloroquine-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of chloroquine-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral tracing experiments demonstrate that these neurons send projections to the ventral periaqueductal gray that are critical in modulation of itch. These findings reveal a cellular and circuit signature of CeA neurons orchestrating behavioral and affective responses to pruritus in mice
Neuronal diversity of the amygdala and the bed nucleus of the stria terminalis
The amygdala complex is a diverse group of more than 13 nuclei, segregated in five major groups: the basolateral (BLA), central (CeA), medial (MeA), cortical (CoA), and basomedial (BMA) amygdala nuclei. These nuclei can be distinguished depending on their cytoarchitectonic properties, connectivity, genetic, and molecular identity, and most importantly, on their functional role in animal behavior. The extended amygdala includes the CeA and the bed nucleus of the stria terminalis (BNST). Both CeA and the BNST share similar cellular organization, including common neuron types, reciprocal connectivity, and many overlapping downstream targets. In this section, we describe the advances of our knowledge on neuronal diversity in the amygdala complex and the BNST, based on recent functional studies, performed at genetic, molecular, physiological, and anatomical levels in rodent models, especially rats and mice. Molecular and connection property can be used separately, or in combinations, to define neuronal populations, leading to a multiplexed neuronal diversity-supporting different functional roles. © 2020 Elsevier B.V
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