Noninvasive Monitoring of Blood Pressure and Heart Rate during Estrous Cycle Phases in Normotensive Wistar-Kyoto and Spontaneously Hypertensive Female Rats.

Since 2015, the National Institutes of Health has called for its funded preclinical research to include both male and female subjects. However, much of the basic animal research that has studied heart rate and blood pressure in the past has used male rats. Male rats have been preferred for these studies to avoid the possible complicating effects of the female estrous cycle. The aim of the current study was to determine whether blood pressure and heart rates vary as a function of the estrous cycle phase of young normotensive Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SHR) female rats. Blood pressure and heart rate were measured at the same time of day throughout the estrous cycle by using a noninvasive tail cuff sphygmomano- metric technique. As expected, 16-wk-old female SHR rats had higher blood pressure and heart rates than did age-matched female WKY rats. However, no significant differences in mean, systolic, or diastolic arterial blood pressure or heart rate were detected across the different stages of the estrous cycle in either strain of female rats. Consistent with previous reports, heart rates were higher and showed less variation in the hypertensive SHR female rats as compared with the normotensive WKY female rats. These results indicate that studies measuring blood pressure and heart rate can include young female SHR and WKY rats with no effect of estrous cycle stage.

Dopamine D2 and Adenosine A2A Receptors Interaction on Ca2+ Current Modulation in a Rodent Model of Parkinsonism.

SUMMARY STATEMENT: A2A receptor required previous D2 receptor activation to modulate Ca2+ currents. Istradefylline decreases pramipexole modulation on Ca2+ currents. Istradefylline reduces A2A + neurons activity in striatial microcircuit, but pramipexole failed to further reduce neuronal activity.

Conceptual framework for neuronal ensemble identification and manipulation related to behavior using calcium imaging.

Significance: The identification and manipulation of spatially identified neuronal ensembles with optical methods have been recently used to prove the causal link between neuronal ensemble activity and learned behaviors. However, the standardization of a conceptual framework to identify and manipulate neuronal ensembles from calcium imaging recordings is still lacking. Aim: We propose a conceptual framework for the identification and manipulation of neuronal ensembles using simultaneous calcium imaging and two-photon optogenetics in behaving mice. Approach: We review the computational approaches that have been used to identify and manipulate neuronal ensembles with single cell resolution during behavior in different brain regions using all-optical methods. Results: We proposed three steps as a conceptual framework that could be applied to calcium imaging recordings to identify and manipulate neuronal ensembles in behaving mice: (1) transformation of calcium transients into binary arrays; (2) identification of neuronal ensembles as similar population vectors; and (3) targeting of neuronal ensemble members that significantly impact behavioral performance. Conclusions: The use of simultaneous two-photon calcium imaging and two-photon optogenetics allowed for the experimental demonstration of the causal relation of population activity and learned behaviors. The standardization of analytical tools to identify and manipulate neuronal ensembles could accelerate interventional experiments aiming to reprogram the brain in normal and pathological conditions.

Striatal Neuronal Ensembles Reveal Differential Actions of Amantadine and Clozapine to Ameliorate Mice L-DOPA-Induced Dyskinesia.

Amantadine and clozapine have proved to reduce abnormal involuntary movements (AIMs) in preclinical and clinical studies of L-DOPA-Induced Dyskinesias (LID). Even though both drugs decrease AIMs, they may have different action mechanisms by using different receptors and signaling profiles. Here we asked whether there are differences in how they modulate neuronal activity of multiple striatal neurons within the striatal microcircuit at histological level during the dose-peak of L-DOPA in ex-vivo brain slices obtained from dyskinetic mice. To answer this question, we used calcium imaging to record the activity of dozens of neurons of the dorsolateral striatum before and after drugs administration in vitro. We also developed an analysis framework to extract encoding insights from calcium imaging data by quantifying neuronal activity, identifying neuronal ensembles by linking neurons that coactivate using hierarchical cluster analysis and extracting network parameters using Graph Theory. The results show that while both drugs reduce LIDs scores behaviorally in a similar way, they have several different and specific actions on modulating the dyskinetic striatal microcircuit. The extracted features were highly accurate in separating amantadine and clozapine effects by means of principal components analysis (PCA) and support vector machine (SVM) algorithms. These results predict possible synergistic actions of amantadine and clozapine on the dyskinetic striatal microcircuit establishing a framework for a bioassay to test novel antidyskinetic drugs or treatments in vitro.

Cortical stimulation relieves parkinsonian pathological activity in vitro.

Previously, we have shown that chemical excitatory drives such as N-methyl-d-aspartate (NMDA) are capable of activating the striatal microcircuit exhibiting neuronal ensembles that alternate their activity producing temporal sequences. One aim of this work was to demonstrate whether similar activity could be evoked by delivering cortical stimulation. Dynamic calcium imaging allowed us to follow the activity of dozens of neurons with single-cell resolution in mus musculus brain slices. A train of electrical stimuli in the cortex evoked network activity similar to the one induced by bath application of NMDA. Previously, we have also shown that the dopamine-depleted striatal microcircuit increases its spontaneous activity generating dominant recurrent ensembles that interrupt the temporal sequences found in control microcircuits. This activity correlates with parkinsonian pathological activity. Several cortical stimulation protocols such as transcranial magnetic stimulation reduce motor signs of Parkinsonism. Here, we show that cortical stimulation in vitro temporarily eliminates the pathological activity from the dopamine-depleted striatal microcircuit by turning off some neurons that sustain this activity and recruiting new ones that allow transitions between network states, similar to the control circuit. When cortical stimulation is given in the presence of L-DOPA, parkinsonian activity is eliminated during the whole recording period. The present experimental evidence suggests that cortical stimulation such as that generated by transcranial magnetic stimulation, or otherwise, may allow reduce L-DOPA dosage.

Subsistema de abastecimiento de agua Chuquiaguillo

Contenido:Cap.I. Recolección de datos: Estudios , informes y proyectos existentes, datos hirdaulicos y operativos del nuevo ambalse. Cap.II. Definición de datos de proyecto: Periodo de diseño, área de diseño, población de diseño, demanda del diseño, ubicación de la nueva planta de tratamiento. Cap.III. Aducción: definición del tipo de aducción, mejoramiento del canal existente, verificación del sifón existente, derivación del caudal, canal de llegada del agua cruda a la planta, resalto hidraulico, obras de mejoramiento del actual canal Incachaca Pampahasi. Cap.IV. Análisis de aguas: Muestreo, análisis de laboratorio, interpretación de resultados. Cap.V. Alternativas de plantas de tratamiento: Investigación bibliográfica, estudio comparativo, conclusiones. Cap.VI. Procesos de tratamiento: Investigación bibliográfica, investigación de laboratorio. Cap.VII. Planta de tratamiento: Descripción del proyecto, memoria de cálculo, dosificación y almacenamiento de productos químicos, cálculo del sistema de bombeo, esquema isométrico de la planta de tratamiento. Cap.VIII. Tanque de regulación: Aducción planta de tratamiento-tanque de regulación, tanque de regulación, accesorios complementarios. Cap.IX. Red de distribución. Cap.X. Costos y presupuestos: Presupuestos de aducción, presupuesto planta de tratamiento, resúmen de costos, conclusiones