Lack of CB1 receptor activity impairs serotonergic negative feedback

Serotonergic and endocannabinoid systems are important substrates for the control of emotional behavior and growing evidence show an involvement in the pathophysiology of mood disorders. In the present study, the absence of the activity of the CB1 cannabinoid receptor impaired serotonergic negative feedback in mice. Thus, in vivo microdialysis experiments revealed increased basal 5-HT extracellular levels and attenuated fluoxetine-induced increase of 5-HT extracellular levels in the prefrontal cortex of CB1 knockout compared to wild-type mice. These observations could be related to the significant reduction in the 5-HT transporter binding site density detected in frontal cortex and hippocampus of CB1 knockout mice. The lack of CB1 receptor also altered some 5-HT receptors related to the 5-HT feedback. Extracellular recordings in the dorsal raphe nucleus revealed that the genetic and pharmacological blockade of CB1 receptor induced a 5-HT1A autoreceptor functional desensitization. In situ hybridization studies showed a reduction in the expression of the 5-HT2C receptor within several brain areas related to the control of the emotional responses, such as the dorsal raphe nucleus, the nucleus accumbens and the paraventricular nucleus of the hypothalamus, whereas an overexpression was observed in the CA3 area of the ventral hippocampus. These results reveal that the lack of CB1 receptor induces a facilitation of the activity of serotonergic neurons in the dorsal raphe nucleus by altering different components of the 5-HT feedback as well as an increase in 5-HT extracellular levels in the prefrontal cortex in mice.

Noninvasive functional and structural exploration of human subcortical structures with high resolution

Projecte de recerca elaborat a partir d’una estada al Max Planck Institute for Human Cognitive and Brain Sciences, Alemanya, entre 2010 i 2012. El principal objectiu d’aquest projecte era estudiar en detall les estructures subcorticals, en concret, el rol dels ganglis basals en control cognitiu durant processament lingüístic i no-lingüístic. Per tal d’assolir una diferenciació minuciosa en els diferents nuclis dels ganglis basals s’utilitzà ressonància magnètica d’ultra-alt camp i alta resolució (7T-MRI). El còrtex prefrontal lateral i els ganglis basals treballant conjuntament per a mitjançar memòria de treball i la regulació “top-down” de la cognició. Aquest circuit regula l’equilibri entre respostes automàtiques i d’alt-ordre cognitiu. Es crearen tres condicions experimentals principals: frases/seqüències noambigües, no-gramatical i ambigües. Les frases/seqüències no-ambigües haurien de provocar una resposta automàtica, mentre les frases/seqüències ambigües i no-gramaticals produïren un conflicte amb la resposta automàtica, i per tant, requeririen una resposta de d’alt-ordre cognitiu. Dins del domini de la resposta de control, la ambigüitat i no-gramaticalitat representen dues dimensions diferents de la resolució de conflicte, mentre per una frase/seqüència temporalment ambigua existeix una interpretació correcte, aquest no és el cas per a les frases/seqüències no-gramaticals. A més, el disseny experimental incloïa una manipulació lingüística i nolingüística, la qual posà a prova la hipòtesi que els efectes són de domini-general; així com una manipulació semàntica i sintàctica que avaluà les diferències entre el processament d’ambigüitat/error “intrínseca” vs. “estructural”. Els resultats del primer experiment (sintax-lingüístic) mostraren un gradient rostroventralcaudodorsal de control cognitiu dins del nucli caudat, això és, les regions més rostrals sostenint els nivells més alts de processament cognitiu

η'-nucleus optical potential and possible η' bound states

Starting from a recent model of the η′N interaction, we evaluate the η ′-nucleus optical potential, including the contribution of lowest order in density, tρ/2mη′, together with the second-order terms accounting for η′ absorption by two nucleons. We also calculate the formation cross section of the η′bound states from (π, p) reactions on nuclei. The η′-nucleus potential suffers from uncertainties tied to the poorly known η′N interaction, which can be partially constrained by the experimental modulus of the η′N scattering length and/or the recently measured transparency ratios in η′nuclear photoproduction. Assuming an attractive interaction and taking the claimed experimental value |aη′N|= 0.1 fm, we obtain an η′optical potential in nuclear matter at saturation density of Vη′=−(8.7 + 1.8i) MeV, not attractive enough to produce η′bound states in light nuclei. Larger values of the scattering length give rise to deeper optical potentials, with moderate enough imaginary parts. For a value |aη′N|= 0.3 fm, which can still be considered to lie within the uncertainties of the experimental constraints, the spectra of light and medium nuclei show clear structures associated to η′-nuclear bound states and to threshold enhancements in the unbound region.

A fully-automatic caudate nucleus segmentation of brain MRI: application in volumetric analysis of pediatric attention-deficit/hyperactivity disorder

Background Accurate automatic segmentation of the caudate nucleus in magnetic resonance images (MRI) of the brain is of great interest in the analysis of developmental disorders. Segmentation methods based on a single atlas or on multiple atlases have been shown to suitably localize caudate structure. However, the atlas prior information may not represent the structure of interest correctly. It may therefore be useful to introduce a more flexible technique for accurate segmentations. Method We present Cau-dateCut: a new fully-automatic method of segmenting the caudate nucleus in MRI. CaudateCut combines an atlas-based segmentation strategy with the Graph Cut energy-minimization framework. We adapt the Graph Cut model to make it suitable for segmenting small, low-contrast structures, such as the caudate nucleus, by defining new energy function data and boundary potentials. In particular, we exploit information concerning the intensity and geometry, and we add supervised energies based on contextual brain structures. Furthermore, we reinforce boundary detection using a new multi-scale edgeness measure. Results We apply the novel CaudateCut method to the segmentation of the caudate nucleus to a new set of 39 pediatric attention-deficit/hyperactivity disorder (ADHD) patients and 40 control children, as well as to a public database of 18 subjects. We evaluate the quality of the segmentation using several volumetric and voxel by voxel measures. Our results show improved performance in terms of segmentation compared to state-of-the-art approaches, obtaining a mean overlap of 80.75%. Moreover, we present a quantitative volumetric analysis of caudate abnormalities in pediatric ADHD, the results of which show strong correlation with expert manual analysis. Conclusion CaudateCut generates segmentation results that are comparable to gold-standard segmentations and which are reliable in the analysis of differentiating neuroanatomical abnormalities between healthy controls and pediatric ADHD.

Efecte del gruix de greix dorsal sobre paràmetres d’interés productiu en truges híbrides i de raça Duroc

En aquest estudi s’ha volgut comprovar l’afectació de la condició corporal de lesfemelles híbrides TB1 (Landrace x Duroc) i de raça pura Duroc de l’empresa SelecciónBatallé en dos moments de la seva vida productiva sobre els rendiments reproductiusposteriors.En concret, s’ha volgut estudiar la relació existent entre un indicador de condiciócorporal, el gruix de greix dorsal (GGD) mesurat en el primer cobriment i en eldeslletament, i els resultats reproductius en el cicles posteriors

Angular distributions of leptons from J/ ψ's produced in 920 GeV fixed-target proton-nucleus collisions

A study of the angular distributions of leptons from decays of J/ψ"s produced in p-C and p-W collisions at s√=41.6~GeV has been performed in the J/ψ Feynman-x region −0.341 GeV/c a significant dependence on the reference frame is found: the polar anisotropy is more pronounced in the Collins-Soper frame and almost vanishes in the helicity frame, where, instead, a significant azimuthal anisotropy arises.

Sciatic and femoral nerve sensory neurones occupy different regions of the L4 dorsal root ganglion in the adult rat.

The topographical distribution of sciatic and femoral nerve sensory neuronal somata in the L4 dorsal root ganglion of the adult rat was mapped after retrograde tracing with one or two of the dyes Fast Blue, Fluoro-Gold, or Diamidino Yellow. The tracers were applied to the proximal transected end of either nerve alone, or from both nerves in the same animal using separate tracers. Three-dimensional reconstructions of the distribution of labelled neurones were made from serial sections of the L4 dorsal root ganglion which is the only ganglion that these two nerves share. The results showed that with little overlap, femoral nerve neurones distribute dorsally and rostrally whereas sciatic nerve neurones distribute medially and ventrally. This finding indicates the existence of a somatotopical organisation for the representation of different peripheral nerves in dorsal root ganglia of adult animals.

The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity

The ascending midbrain 5-HT neurons to the forebrain may be dysregulated in depression and have a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by coimmunoprecipitation and colocation of the FGFR1 and 5-HT1A immunoreactivities in the midbrain raphe cells, evidence for the existence of FGFR1-5-HT1A receptor heterocomplexes in the dorsal and median raphe nuclei of the Sprague Dawley rat as well as in the rat medullary raphe RN33B cells has been obtained. Especially after combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA clusters was found in the RN33B cells. Similar results were reached with the FRET technique in HEK293T cells, where TM-V of the 5HT1A receptor was found to be part of the receptor interface. The combined treatment with FGF-2 and the 5-HT1A agonist also synergistically increased FGFR1 and ERK1/2 phosphorylation in the raphe midline area of the midbrain and the RN33B cells as well as their differentiation, as seen from development of the increased number and length of extensions per cell and their increased 5-HT immunoreactivity. These signaling and differentiation events were dependent on the receptor interface since they were blocked by incubation with TM-V but not by TM-II. Together, the results indicate that the 5-HT1A autoreceptors by being part of a FGFR1-5-HT1A receptor heterocomplex in the midbrain raphe 5-HT nerve cells appear to have a trophic role in the central 5-HT neuron systems in addition to playing a key role in reducing the firing of these neurons

On the existence and function of galanin receptor heteromers in the central nervous system

Galanin receptor (GalR) subtypes 1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1-5-HT1A heteromers in cellular models with trans-inhibition of the protomer signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1-GalR2-5-HT1A heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1-29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1-GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer. Finally, putative GalR-α2-adrenoreceptor heteromers with antagonistic receptor-receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression

Efficacy of the fluorescent dyes Fast Blue, Fluoro-Gold, and Diamidino Yellow for retrograde tracing to dorsal root ganglia after subcutaneous injection

The present study was designed to investigate the efficacy of the fluorescent dyes Fast Blue (FB), Fluoro-Gold (FG), and Diamidino Yellow (DY) for retrograde tracing of lumbar dorsal root ganglia after their subcutaneous injection into different hindlimb digits. Injection of equal volumes (0.5 mu l) of 5% FB or 2% FG resulted in similar mean numbers of sensory neurones labelled by each tracer. Injection of equal volumes (0.5 mu l) of FB or FG in a single digit followed 10 days later by a second injection of the same volume of 5% DY into the same digit resulted in similar mean numbers of labelled sensory neurones for each of the three tracers. Furthermore, on average, 75% of all the FB-labelled cells and 74% of all FC-labelled cells also contained DY. Repeating the same experiment with an increased volume of DY (1.5 mu l) resulted in an increase in the mean number of double-labelled profiles to 82 and 84% for FB and FG, respectively. The results show that FB, FG and DY label similar numbers of cutaneous afferents and that a high level of double labelling may be obtained after sequential injections in digits. These properties make them suitable candidates in investigations where a combination of tracers with similar labelling efficacies is needed.

Morfoestructura y evolución del ramal N160 de la dorsal de la Cuenca Nor-Fidjiana (Pacífico sudoeste)

La campaña oceanográfica franco-japonesa Yokosuka 90, llevada a cabo del 10 de Enero al 6 de Febrero de 1991, tuvo por objeto el estudio geológico y geofísico del segmento de segundo orden o ramal de dirección N160 de la dorsal de la Cuenca Nor-Fidjiana (Pacífico sudoeste). Este ramal es especialmente interesante, no sólo por estar situado en una cuenca de tras-arco, sino también en el marco de las hipótesis que intentan establecer las relaciones entre tasas de expansión y morfoestructura en las dorsales oceánicas. Así, en el ramal estudiado coinciden una tasa de expansión intermedia (5 cm/a) y una morfología típica de dorsal lenta. Dicho ramal, segmentado y constituido por una sucesión de crestas y de grabens desplazados lateralmente, se sitúa entre dos puntos mples, uno de tipo dorsal-dorsal-zona de fractura (RRF), al sur, y otro, de tipo dorsal-dorsal-dorsal (RRR), al norte. El ramal N160 de la Cuenca Nor-Fidjiana es, por otra parte, extremadamente joven ya que de acuerdo con las anomalías magnéticas se habna formado durante un episodio volcano-tectónico iniciado hace menos de 1 Ma.

Caracterización geológica de la región de enlace entre la Cuenca de Bransfield y la Dorsal Sur de Scotia (Antártida)

La Dorsal Sur de Scotia (DSS) constituye une frontera de placas transformante con sentido senestral, que limita las placas de Scotia, al norte, y Antártica, al sur. Durante la campaña de geología y geofísica marinas 'Scotia 92', realizada en Febrero de 1992 a bordo del BIO Hespérides, se ha estudiado su extremo occidental y sectores próximos a la Cuenca de Bransfield, entre el margen nor-occidental de la Península Antártica y las islas Shetland del Sur, Elefante y Orcadas del Sur. Al norte y sur de la DSS se desarrollan las cuencas de Scotia y de Powell, respectivamente. Los datos de sísmica de multicanal, magnetismo y gravimetna obtenidos muestran caracteristicas diferenciales entre ambas cuencas. La morfoestructura de la DSS, formada por dos crestas paralelas separadas por una profunda depresión axial, ha sido recubierta mediante perfilaje de multihaz con el sistema SIMRAD EM-12 en una área de 50 x 100 km. La batimetría resultante ha permitido reconocer en detalle las caracteristicas de una depresión de más de 5.300 m de profundidad y de 10 a 30 km de anchura, bautizada como Fosa Hespérides. En ella se aprecia la existencia de dos famílias de lineaciones, la primera de dirección E-W y paralela al límite de placas, y la segunda de dirección NW-SE. La primera acomodaría el movimiento cizallante regional mientras que la segunda estaría asociada con una componente extensional probablemente relacionada con la dirección de la Cuenca de Bransfield. La forma romboédrica de la fosa está determinada por la interacción de ambas famílias de lineaciones. Teniendo en cuenta que el límite de placas transcurre entre las dos crestas, interpretamos la Fosa Hespérides como una cuenca de pull-apart desarrollada como consecuencia del movimiento de cizalla a lo largo de la DSS.

Probing quantum gravity using photons from a flare of the active galactic nucleus Markarian 501 observed by the MAGIC telescope

We analyze the timing of photons observed by the MAGIC telescope during a flare of the active galactic nucleus Mkn 501 for a possible correlation with energy, as suggested by some models of quantum gravity (QG), which predict a vacuum refractive index similar or equal to 1 + (E/M-QGn)(n), n = 1, 2. Parametrizing the delay between gamma-rays of different energies as Delta t = +/-tau E-1 or Delta t = +/-tau E-q(2), we find tau(1) = (0.030 +/- 0.012) s/GeV at the 2.5-sigma level, and tau(q) = (3.71 +/- 2.57) x 10(-6) s/GeV2, respectively. We use these results to establish lower limits M-QG1 > 0.21 X 10(18) GeV and M-QG2 > 0.26 x 10(11) GeV at the 95% C.L. Monte Carlo studies confirm the MAGIC sensitivity to propagation effects at these levels. Thermal plasma effects in the source are negligible, but we cannot exclude the importance of some other source effect.

Nucleus accumbens is involved in human action monitoring: evidence from invasive electrophysiological recordings

The Nucleus accumbens (Nacc) has been proposed to act as a limbic-motor interface. Here, using invasive intraoperative recordings in an awake patient suffering from obsessive-compulsive disease (OCD), we demonstrate that its activity is modulated by the quality of performance of the subject in a choice reaction time task designed to tap action monitoring processes. Action monitoring, that is, error detection and correction, is thought to be supported by a system involving the dopaminergic midbrain, the basal ganglia, and the medial prefrontal cortex. In surface electrophysiological recordings, action monitoring is indexed by an error-related negativity (ERN) appearing time-locked to the erroneous responses and emanating from the medial frontal cortex. In preoperative scalp recordings the patient's ERN was found to be signifi cantly increased compared to a large (n = 83) normal sample, suggesting enhanced action monitoring processes. Intraoperatively, error-related modulations were obtained from the Nacc but not from a site 5 mm above. Importantly, crosscorrelation analysis showed that error-related activity in the Nacc preceded surface activity by 40 ms. We propose that the Nacc is involved in action monitoring, possibly by using error signals from the dopaminergic midbrain to adjust the relative impact of limbic and prefrontal inputs on frontal control systems in order to optimize goal-directed behavior.

Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects

The ventral striatum / nucleus accumbens has been implicated in the craving for drugs and alcohol which is a major reason for relapse of addicted people. Craving might be induced by drug-related cues. This suggests that disruption of craving-related neural activity in the nucleus accumbens may significantly reduce craving in alcohol-dependent patients. Here we report on preliminary clinical and neurophysiological evidence in three male patients who were treated with high frequency deep brain stimulation of the nucleus accumbens bilaterally. All three had been alcohol dependent for many years, unable to abstain from drinking, and had experienced repeated relapses prior to the stimulation. After the operation, craving was greatly reduced and all three patients were able to abstain from drinking for extended periods of time. Immediately after the operation but prior to connection of the stimulation electrodes to the stimulator, local field potentials were obtained from the externalized cables in two patients while they performed cognitive tasks addressing action monitoring and incentive salience of drug related cues. LFPs in the action monitoring task provided further evidence for a role of the nucleus accumbens in goal-directed behaviors. Importantly, alcohol related cue stimuli in the incentive salience task modulated LFPs even though these cues were presented outside of the attentional focus. This implies that cue-related craving involves the nucleus accumbens and is highly automatic.