GABAergic inhibition in the fear conditioning circuit of the lateral amygdala is potentiated by dopamine D1 agonists

Auditory fear conditioning is dependent on auditory signaling from the medial geniculate (MGm) and the auditory cortex (TE3) to principal neurons of the lateral amygdala (LA). Local circuit GABAergic interneurons are known to inhibit LA principal neurons via fast and slow IPSP's. Stimulation of MGm and TE3 produces excitatory post-synaptic potentials in both LA principal and interneurons, followed by inhibitory post-synaptic potentials. Manipulations of D1 receptors in the lateral and basal amygdala modulate the retrieval of learned association between an auditory CS and foot shock. Here we examined the effects of D1 agonists on GABAergic IPSP's evoked by stimulation of MGm and TE3 afferents in vitro. Whole cell patch recordings were made from principal neurons of the LA, at room temperature, in coronal brain slices using standard methods. Stimulating electrodes were placed on the fiber tracts medial to the LA and at the external capsule/layer VI border dorsal to the LA to activate (0.1-0.2mA) MGm and TE3 afferents respectively. Neurons were held at -55.0 mV by positive current injection to measure the amplitude of the fast IPSP. Changes in input resistance and membrane potential were measured in the absence of current injection. Stimulation of MGm or TE3 afferents produced EPSP's in the majority of principal neurons and in some an EPSP/IPSP sequence. Stimulation of MGm afferents produced IPSP's with amplitudes of -2.30 ± 0.53 mV and stimulation of TE3 afferents produced IPSP's with amplitudes of -1.98 ± 1.26 mV. Bath application of 20μM SKF38393 increased IPSP amplitudes to -5.94 ± 1.62 mV (MGm, n=3) and-5.46 ± 0.31 mV (TE3, n=3). Maximal effect occurred <10mins. A small increase in resting membrane potential and decrease in input resistance were observed. These data suggest that DA modulates both the auditory thalamic and auditory cortical inputs to the LA fear conditioning circuit via local GABAergic circuits. Supported by NIMH Grants 00956, 46516, and 58911.

Comparison of measured sleeping metabolic rate and predicted basal metabolic rate during the first year of life : evidence of a bias changing with increasing metabolic rate

Objective: To compare measurements of sleeping metabolic rate (SMR) in infancy with predicted basal metabolic rate (BMR) estimated by the equations of Schofield. Methods: Some 104 serial measurements of SMR by indirect calorimetry were performed in 43 healthy infants at 1.5, 3, 6, 9 and 12 months of age. Predicted BMR was calculated using the weight only (BMR-wo) and weight and height (BMR-wh) equations of Schofield for 0-3-y-olds. Measured SMR values were compared with both predictive values by means of the Bland-Altman statistical test. Results: The mean measured SMR was 1.48 MJ/day. The mean predicted BMR values were 1.66 and 1.47 MJ/day for the weight only and weight and height equations, respectively. The Bland-Altman analysis showed that BMR-wo equation on average overestimated SMR by 0.18 MJ/day (11%) and the BMR-wh equation underestimated SMR by 0.01 MJ/day (1%). However the 95% limits of agreement were wide: -0.64 to + 0.28 MJ/day (28%) for the former equation and -0.39 to + 0.41 MJ/day (27%) for the latter equation. Moreover there was a significant correlation between the mean of the measured and predicted metabolic rate and the difference between them. Conclusions: The wide variation seen in the difference between measured and predicted metabolic rate and the bias probably with age indicates there is a need to measure actual metabolic rate for individual clinical care in this age group.

Dr. William Levison (seated, far left) with other U.S. Army medial doctors and nurses with Christmas Tree in background Portraits Groups

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Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

Background: Adenosine is a potent sleep-promoting substance, and one of its targets is the basal forebrain. Fairly little is known about its mechanism of action in the basal forebrain and about the receptor subtype mediating its regulating effects on sleep homeostasis. Homeostatic deficiency might be one of the causes of the profoundly disturbed sleep pattern in major depressive disorder, which could explain the reduced amounts of delta-activity-rich stages 3 and 4. Since major depression has a relatively high heritability, and on the other hand adenosine regulates sleep homeostasis and might also be involved in mood modulation, adenosine-related genes should be considered for their possible contribution to a predisposition for depression and disturbed sleep in humans. Depression is a complex disorder likely involving the abnormal functioning of several genes. Novel target genes which could serve as the possible common substrates for depression and comorbid disturbed sleep should be identified. In this way specific brain areas related to sleep regulation should be studied by using animal model of depression which represents more homogenous phenotype as compared to humans. It is also important to study these brain areas during the development of depressive-like features to understand how early changes could facilitate pathophysiological changes in depression. Aims and methods: We aimed to find out whether, in the basal forebrain, adenosine induces recovery non-rapid eye movement (NREM) sleep after prolonged waking through the A1 or/and A2A receptor subtype. A1 and A2A receptor antagonists were perfused into the rat basal forebrain during 3 h of sleep deprivation, and the amount of NREM sleep and delta power during recovery NREM sleep were analyzed. We then explored whether polymorphisms in genes related to the metabolism, transport and signaling of adenosine could predispose to depression accompanied by signs of disturbed sleep. DNA from 1423 individuals representative of the Finnish population and including controls and cases with depression, depression accompanied by early morning awakenings and depression accompanied by fatigue, was used in the study to investigate the possible association between polymorphisms from adenosine-related genes and cases. Finally to find common molecular substrates of depression and disturbed sleep, gene expression changes were investigated in specific brain areas in the rat clomipramine model of depression. We focused on the basal forebrain of 3-week old clomipramine-treated rats which develop depressive-like symptoms later in adulthood and on the hypothalamus of adult female clomipramine-treated rats. Results: Blocking of the A1 receptor during sleep deprivation resulted in a reduction of the recovery NREM sleep amount and delta power, whereas A2A receptor antagonism had no effect. Polymorphisms in adenosine-related genes SLC29A3 (equilibrative nucleoside transporter type 3) in women and SLC28A1 (concentrative nucleoside transporter type 1) in men associated with depression alone as well as when accompanied by early morning awakenings and fatigue. In Study III the basal forebrain of postnatal rats treated with clomipramine displayed disturbances in gamma-aminobutyric acid (GABA) receptor type A signaling, in synaptic transmission and possible epigenetic changes. CREB1 was identified as a common transcription denominator which also mediates epigenetic regulation. In the hypothalamus the major changes included the expression of genes in GABA-A receptor pathway, K+ channel-related, glutamatergic and mitochondrial genes, as well as an overexpression of genes related to RNA and mRNA processing. Conclusions: Adenosine plays an important role in sleep homeostasis by promoting recovery NREM sleep via the A1 receptor subtype in the basal forebrain. Also adenosine levels might contribute to the risk of depression with disturbed sleep, since the genes encoding nucleoside transporters showed the strongest associations with depression alone and when accompanied by signs of disturbed sleep in both women and men. Sleep and mood abnormalities in major depressive disorder could be a consequence of multiple changes at the transcriptional level, GABA-A receptor signaling and synaptic transmission in sleep-related basal forebrain and the hypothalamus.

An Experimental and Numerical Study of Calliphora Wing Structure

Experiments are performed to determine the mass and stiffness variations along the wing of the blowfly Calliphora. The results are obtained for a pairs of wings of 10 male flies and fresh wings are used. The wing is divided into nine locations along the span and seven locations along the chord based on venation patterns. The length and mass of the sections is measured and the mass per unit length is calculated. The bending stiffness measurements are taken at three locations, basal (near root), medial and distal (near tip) of the fly wing. Torsional stiffness measurements are also made and the elastic axis of the wing is approximately located. The experimental data is then used for structural modeling of the wing as a stepped cantilever beam with nine spanwise sections of varying mass per unit lengths, flexural rigidity (EI) and torsional rigidity (GJ) values. Inertial values of nine sections are found to approximately vary according to an exponentially decreasing law over the nine sections from root to tip and it is used to calculate an approximate value of Young's modulus of the wing biomaterial. Shear modulus is obtained assuming the wing biomaterial to be isotropic. Natural frequencies, both in bending and torsion, are obtained by solving the homogeneous part of the respective governing differential equations using the finite element method. The results provide a complete analysis of Calliphora wing structure and also provide guidelines for the biomimetic structural design of insect-scale flapping wings.

Interior Medial Axis Transform computation of 3D objects bound by free-form surfaces

This paper presents an algorithm for generating the Interior Medial Axis Transform (iMAT) of 3D objects with free-form boundaries. The algorithm proposed uses the exact representation of the part and generates an approximate rational spline description of the iMAT. The algorithm generates the iMAT by a tracing technique that marches along the object's boundary. The level of approximation is controlled by the choice of the step size in the tracing procedure. Criteria based on distance and local curvature of boundary entities are used to identify the junction points and the search for these junction points is done in an efficient way. The algorithm works for multiply-connected objects as well. Results of the implementation are provided. (C) 2010 Elsevier Ltd. All rights reserved.

Neuropeptide Y structure is modulated by aluminium in the hypothalamus

Aluminium is an element suspected to contribute to the pathogenesis of Alzheimer's disease, but its mechanism of action is not clear. Neuropeptide Y (NPY) plays a significant role in feeding behaviour. Our spectroscopic, ELISA, and western blot studies indicate that aluminium interacts with neuropeptide Y and alters significantly the a-helical content. We found that aluminium reduced levels of NPY in the hypothalamus of aged rabbits. NPY polyclonal antibody interaction was found to depend upon the alpha-helical content of NPY. These results clearly show that aluminium alters NPY structure and this could explain the abnormality in feeding behaviour seen in patients with Alzheimer's disease.

Queuing of concurrent movement plans by Basal Ganglia

How the brain converts parallel representations of movement goals into sequential movements is not known. We tested the role of basal ganglia (BG) in the temporal control of movement sequences by a convergent approach involving inactivation of the BG by muscimol injections into the caudate nucleus of monkeys and assessing behavior of Parkinson's disease patients, performing a modified double-step saccade task. We tested a critical prediction of a class of competitive queuing models that explains serial behavior as the outcome of a selection of concurrently activated goals. In congruence with these models, we found that inactivation or impairment of the BG unmasked the parallel nature of goal representations such that a significantly greater extent of averaged saccades, curved saccades, and saccade sequence errors were observed. These results suggest that the BG perform a form of competitive queuing, holding the second movement plan in abeyance while the first movement is being executed, allowing the proper temporal control of movement sequences.

Efecto de la suplementacion con Moringa oleifera sobre el comportamiento productivo de ovinos alimentados con una dieta basal de pasto guinea (Panicum maximum Jacq)

El presente estudio se realizó en la finca “Santa Rosa” propiedad de la Universidad Nacional Agraria, localizada geográficamente a los 12°08’15’’ latitud Norte y a los 86°09’36’’ longitud Este, en el departamento de Managua, con el objetivo de evaluar el comportamiento productivo de ovinos alimentados con una dieta basal de pasto guinea (Panicum máximum Jacq) y suplementados con diferentes niveles de Moringa oleífera. Se utilizaron 18 corderos mestizos (Pelibuey x Blackbelly) con pesos iníciales promedio de 20 ± 2 kg, los cuales fueron desparasitados, vitaminados y distribuidos en un Diseño Completamente Aleatorio con tres tratamientos: TI Panicum máximumad-libitum, TII P. máximum ad-libitum + 0.35 kg MSM. oleífera, TIII P. máximum ad-libitum + 0.50 kg MSM. oleífera. Las variables estudiadas fueron: consumo diario de MS, ganancia media diaria y conversión alimenticia. Se realizó análisis de varianza y comparaciones de medias con la Prueba de Tukey utilizando MINITAB, versión 12.0. Los resultados de los análisis de varianza (P<0,05) mostraron que el m ayor consumo total de MS, ganancia media diaria y conversión alimenticia se obtiene con el TIII (0.8 kg MS/animal/día, 117.97 g/animal/día y 6.78) el que difiere e stadísticamente (P< 0.01) del TI (0.57 kg MS/animal/día, 30.85 g/animal/día y 18.47) pero no difiere significativamente (P> 0.05)del TII (0.73 kg MS/animal/día, 90.91 g/animal/día y 8.02).En conclusión el forraje de M. oleífera como suplemento proteico para ovinos consumiendo una dieta basal de P.máximum incrementa la ganancia de peso y mejora el consumo total de MS y la conversión alimenticia.

Efecto de la suplementación con Moringa oleifera sobre el comportamiento productivo de ovinos alimentados con una dieta basal de pasto guinea (Panicum maximun Jacq.)

El presente estudio se realizó en la finca Santa Rosa propiedad de la Universidad Nacional Agraria, localizada geográficamente en los 12°08’15’’ latitud Norte y 86°09’36’’ longitud Este, en el Departamento de Managua, Nicaragua con el objetivo de evaluar el comportamiento productivo de ovinos alimentados con una dieta basal de pasto guinea ( Panicum máximum Jacq) y suplementados con diferentes niveles de Moringa oleífera . Se utilizaron 18 corderos mestizos (Pelibuey x Black belly) con pesos iníciales promedio de 20 ± 2 kg, los cuales fueron desparasitados, vitaminados y distribuidos en un Diseño Completamente Aleatorio con tres tratamientos: Panicum máximum ad-libitum , P. máximum ad-libitum + 0.35 kg MS M. oleífera , y P. máximum ad-libitum + 0.50 kg MS M. oleífera . Las variables estudiadas fueron: consumo total de MS (CTMS), ganancia media diaria (GMD) y conversión alimenticia (CA). Se realizó análisis de varianza y comparaciones de medias con la Prueba de Tukey utilizando MINITAB, versión 12.0. Los resultados de los análisis de varianza (P<0,05) mostraron que el mejor CTMS, GMD y CA se obtiene con la utilización de P. máximum ad-libitum + 0.50 kg MS M. oleífera (0.8 kg MS/animal/día, 117.97 g/animal/día y 6.78), el que difiere estadísticamente (P< 0.05) del tratamiento con Panicum máximum ad-libitum , (0.57 kg MS/animal/día, 30.85 g/ animal/día y 18.47) pero (P> 0.05) del tratamiento P. máximum ad-libitum + 0.35 kg MS M. oleífera , (0.73 kg MS/animal/día, 90.91 g/animal/día y 8.02). En conclusión el forraje de M. oleifera como suplemento proteico para ovinos consumiendo una dieta basal de P. máximum incrementa la ganancia de peso y mejora el consumo total de MS y la conversión alimenticia.

Evaluación de las técnicas quirúrgicas medial VS la técnica lateral en ovariohisterectomía en la especie canina en el municipio de Camoapa, 2014.

El presente trabajo de investigación fue realizado en la ciudad de Camoapa, municipio del Departamento de Boaco, Republica de Nicaragua; el mismo que tuvo como objetivo determinar la técnica quirúrgica de esterilización más adecuada para una pronta recuperación del paciente, tomándose como muestra a 12 hembras canina, cuyas edades fueron comprendidas desde los 6 meses hasta los 24 meses de edad de toda raza. Las técnicas empleadas fueron la técnica medial y la técnica lateral, el tamaño requerido de la población para este trabajo fue de 12 hembras caninas las cuales se dividieron en cuatro grupos de 3 animales para cada grupo, generando 7 observaciones para cada grupo. Dichas intervenciones siguieron un protocolo de asepsia, anestesia y quirúrgico. De esta manera de acuerdo, a los procedimientos estadísticos se desprendieron las siguientes conclusiones: no existe una interacción entre la edad, las técnicas y el tiempo de recuperación del paciente post–quirurgico. Por otra parte, al evaluar la variable de cicatrización, se demostró que los caninos de menor edad tienen una mejor respuesta a la intervención quirúrgica. Y en conclusión para tener una cicatrización en menor tiempo, se recomienda aplicar una laparotomía lateral, en perras de cualquier edad, por cuanto la técnica utilizada y el tiempo de cicatrización se comportan de manera independiente en relación a la edad del animal.

Sample-specific behavior in failure models of disordered medial

The concept ''sample-specific'' is suggested to describe the behavior of disordered media close to macroscopic failure. it is pointed out that the transition from universal scaling to sample-specific behavior may be a common phenomenon in failure models of disordered media. The dynamical evolution plays an important role in the transition.