Temporal dynamics and neuronal specificity of Grin3a expression in the mouse forebrain

GluN3A subunits endow N-Methyl-D-Aspartate receptors (NMDARs) with unique biophysical, trafficking, and signaling properties. GluN3A-NMDARs are typically expressed during postnatal development, when they are thought to gate the refinement of neural circuits by inhibiting synapse maturation, and stabilization. Recent work suggests that GluN3A also operates in adult brains to control a variety of behaviors, yet a full spatiotemporal characterization of GluN3A expression is lacking. Here, we conducted a systematic analysis of Grin3a (gene encoding mouse GluN3A) mRNA expression in the mouse brain by combining high-sensitivity colorimetric and fluorescence in situ hybridization with labeling for neuronal subtypes. We find that, while Grin3a mRNA expression peaks postnatally, significant levels are retained into adulthood in specific brain regions such as the amygdala, medial habenula, association cortices, and high-order thalamic nuclei. The time-course of emergence and down-regulation of Grin3a expression varies across brain region, cortical layer of residence, and sensory modality, in a pattern that correlates with previously reported hierarchical gradients of brain maturation and functional specialization. Grin3a is expressed in both excitatory and inhibitory neurons, with strong mRNA levels being a distinguishing feature of somatostatin interneurons. Our study provides a comprehensive map of Grin3a distribution across the murine lifespan and paves the way for dissecting the diverse functions of GluN3A in health and disease. circuit refinement, excitatory glycine receptors, high-order thalamus, neocortical maturation, somatostatin interneuron

Neuronal tangential migration from Nkx2.1-positive hypothalamus

During the development of the central nervous system, the immature neurons suffer different migration processes. It is well known that Nkx2.1-positive ventricular layer give rise to critical tangential migrations into different regions of the developing forebrain. Our aim was to study this phenomenon in the hypothalamic region. With this purpose, we used a transgenic mouse line that expresses the tdTomato reporter driven by the promotor of Nkx2.1. Analysing the Nkx2.1-positive derivatives at E18.5, we found neural contributions to the prethalamic region, mainly in the zona incerta and in the mes-diencephalic tegmental region. We studied the developing hypothalamus along the embryonic period. From E10.5 we detected that the Nkx2.1 expression domain was narrower than the reporter distribution. Therefore, the Nkx2.1 expression fades in a great number of the early-born neurons from the Nkx2.1-positive territory. At the most caudal positive part, we detected a thin stream of positive neurons migrating caudally into the mes-diencephalic tegmental region using time-lapse experiments on open neural tube explants. Late in development, we found a second migratory stream into the prethalamic territory. All these tangentially migrated neurons developed a gabaergic phenotype. In summary, we have described the contribution of interneurons from the Nkx2.1-positive hypothalamic territory into two different rostrocaudal territories: the mes-diencephalic reticular formation through a caudal tangential migration and the prethalamic zona incerta complex through a dorsocaudal tangential migratio

Shh dependent and independent maintenance of basal midbrain

Sonic hedgehog (Shh) is well known as the molecule responsible for the induction and maintenance of ventral neural tube structures. Recent data have shown that ventral neuronal populations react differentially to the amount of this morphogen not only in the spinal cord, but also in more rostral parts of the brain, like the midbrain. A dorsal expansion in the Shh expression domain modifies the differentiation program in this territory. The lack of Shh produces alterations in the development of this area as well. Here, for the first time, we analyze in detail the development of the different mesencephalic basal nuclei in the absence of Shh. We report that the oculomotor complex is lost, the dopaminergic populations are strongly affected but the red nucleus is maintained. These results point out that not all the midbrain neuronal populations are dependent on Shh for their maintenance, as previously thought. Based on our results and recently published data, we suggest the existence of a specific genetic pathway for the specification of the mesencephalic red nucleus. Foxa2 could be the candidate gene that might control this genetic pathway.This study was supported by grants from MEC (BFU2008-00588), Eurexpress (LSHG-CT-2004-512003-EC), FIS program (G03/210, G03/056) to S.M.; MEC (BFU2008-03708/BFI) to E.P. and Ingenio 2010 MEC-Consolider CSD2007-0023. A.P.B. was supported by TV3 Marató (062232) and E.P. was supported by ‘‘Ramón y Cajal’’ Program (MEC).Peer Reviewe

The amniote oculomotor complex

The oculomotor (OM) complex is a combination of somatic and parasympatethic neurons. The correct development and wiring of this cranial pair is essential to perform basic functions: eyeball and eyelid movements, pupillary constriction, and lens accommodation. The improper formation or function of this nucleus leads pathologies such as strabismus. We describe the OM organization and function in different vertebrate brains, including chick, mouse, and human. The morphological localization is detailed, as well as the spatial relation with the trochlear nucleus in order to adjust some misleading anatomical topographic descriptions. We detailed the signaling processes needed for the specification of the OM neurons. The transcriptional programs driven the specification and differentiation of these neurons are partially determined. We summarized recent genetic studies that have led to the identification of guidance mechanisms involved in the migration, axon pathfinding, and targeting of the OM neurons. Finally, we overviewed the pathology associated to genetic malformations in the OM development and related clinical alterations.Grant sponsors: Ministerio de Ciencia e Innovacion (FEDER); Grant number: BFU2013-48230; GENERALITAT VALENCIANA (FEDER); Grant number: PROMETEOII/2014/014; Red de Terapia Celular (FEDER); Grant number: RD16/ 001/0010; Ministerio de Educacion, Cultura y Deporte (FPU program); Grant number: FPU16/03853Peer reviewe

Dynamic expression patterns of Nkx6.1 and Nkx6.2 in the developing mes-diencephalic basal plate

8 p., 5 figures and references.The components of the molecular codes needed to specify the different neuronal populations present in the basal neural tube are being identified. These codes become more intricate as we move to more anterior regions of the central nervous system. The aim of this study is to thoroughly analyze the expression pattern of Nkx6.1, Nkx6.2, and Pou4f1. These three genes are candidates to play an important role in the determination and differentiation of the basal nuclei of the mesencephalon and diencephalon. The results obtained have shown that there is a longitudinal domain positive for both Nkx6.1 and Nkx6.2 that is medial to the Pou4f1-positive red nucleus. This domain could correspond to part of the reticular formation, which extends from the diencephalon and the mesencephalon. The nuclei integrated in this domain would be the rostral interstitial nucleus, the interstitial nucleus of Cajal, and a mesencephalic equivalent to these nuclei.Grant sponsor: MICINN; Grant numbers: BFU2008-03708/BFI, BFU2008-00588, CSD2007-00023; Grant sponsor: TV3 Marato; Grant number: 062232; Grant sponsor: European Commission; Grant number: LSHG-CT-2004-512003.Peer reviewe

Patrón de expresión génica e histogénesis en la placa basal del prosencéfalo y mesencéfalo de aves / Eduardo Puelles Martínez de la Torre ; Directores, John L.R. Rubenstein, Salvador Martínez Pérez.

Tesis - Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 694.Consulte la tesis en: BCA. GENERAL. DEPOSITO. T.M-2132

Role of Shh in the development of molecularly characterized tegmental nuclei in mouse rhombomere 1

Hindbrain rhombomeres in general are differentially specified molecularly by unique combinations of Hox genes with other developmental genes. Rhombomere 1 displays special features, including absence of Hox gene expression. It lies within the hindbrain range of the Engrailed genes (En1, En2), controlled by the isthmic organizer via diffusion of FGF8. It is limited rostrally by the isthmus territory, and caudally by rhombomere 2. It is double the normal size of any other rhombomere. Its dorsal part generates the cerebellar hemispheres and its ventral part gives rise to several populations, such as some raphe nuclei, the interpeduncular nucleus, the rhabdoid nucleus, anterior, dorsal, ventral and posterodorsal tegmental nuclei, the cholinergic pedunculopontine and laterodorsal tegmental nuclei, rostral parts of the hindbrain reticular formation, the locus coeruleus, and part of the lateral lemniscal and paralemniscal nuclei, among other formations. Some of these populations migrate tangentially before reaching their final positions. The morphogen Sonic Hedgehog (Shh) is normally released from the local floor plate and underlying notochord. In the present report we explore, first, whether Shh is required in the specification of these r1 populations, and, second, its possible role in the guidance of tangentially migrating neurons that approach the midline. Our results indicate that when Shh function is altered selectively in a conditional mutant mouse strain, most populations normally generated in the medial basal plate of r1 are completely absent. Moreover, the relocation of some neurons that normally originate in the alar plate and migrate tangentially into the medial basal plate is variously altered. In contrast, neurons that migrate radially (or first tangentially and then radially) into the lateral basal plate were not significantly affected.Work supported by “Ministerio de Economía y Competitividad” BFU2010-16548 (FEDER Fonds) to E. Puelles, Consolider Grant (CSD2007-00023) and European commission (EUCOMMTOOLS, contract 261492) to S.M., and “Ministerio de Economía y Competitividad” grant BFU2008-01456 and Fundación SENECA contract 04548/GERM/06 (no. 10891) to L. Puelles. J.A. Moreno-Bravo was supported by the Predoctoral Program of the “Consejo Superior de Investigaciones Científicas-Junta de Ampliación de Estudios”, co-financed by the European Social Fund.Peer reviewe

¿Cómo afecta la introducción de las metodologías del Aprendizaje Cooperativo y del Aprendizaje Basado en Proyectos en la opinión de los/las estudiantes sobre su profesorado

XX1 CUIEET - Congreso Universitario de Innovación Educativa en las Enseñanzas Técnicas, Valencia, 2013.[ES] En este artículo se presentan los resultados percibidos por los y las estudiantes derivados de la aplicación de metodologías del aprendizaje cooperativo y del aprendizaje basado en proyectos en varias asignaturas de los grados en ingeniería mecánica, en electricidad, en electrónica industrial y automática y en química industrial. A mayor dedicación de tiempo en la asignatura a dichas metodologías, mejores resultados se obtienen, una mayor implicación del alumnado en su aprendizaje, una mayor motivación e interés, y, en definitiva, una mejor percepción de la docencia del profesorado.[EN] This article presents the results perceived by students derived from the application of methodologies of cooperative learning and project based learning in multiple subjects of degrees in engineering mechanics, electricity, industrial electronics and chemical. The greater the dedication of time on the subject to these methodologies, the better the results are obtained, greater involvement of the students in their learning, greater motivation and interest, and, ultimately, a better perception of the teaching of the faculty.Servicio de Asesoramiento Educativo de la UPV/EHU (Proyectos de innovación educativa

¿Cómo afecta la introducción de las metodologías del Aprendizaje Cooperativo y del Aprendizaje Basado en Proyectos en la opinión de los/las estudiantes sobre su profesorado

XX1 CUIEET - Congreso Universitario de Innovación Educativa en las Enseñanzas Técnicas, Valencia, 2013.[ES] En este artículo se presentan los resultados percibidos por los y las estudiantes derivados de la aplicación de metodologías del aprendizaje cooperativo y del aprendizaje basado en proyectos en varias asignaturas de los grados en ingeniería mecánica, en electricidad, en electrónica industrial y automática y en química industrial. A mayor dedicación de tiempo en la asignatura a dichas metodologías, mejores resultados se obtienen, una mayor implicación del alumnado en su aprendizaje, una mayor motivación e interés, y, en definitiva, una mejor percepción de la docencia del profesorado.[EN] This article presents the results perceived by students derived from the application of methodologies of cooperative learning and project based learning in multiple subjects of degrees in engineering mechanics, electricity, industrial electronics and chemical. The greater the dedication of time on the subject to these methodologies, the better the results are obtained, greater involvement of the students in their learning, greater motivation and interest, and, ultimately, a better perception of the teaching of the faculty.Servicio de Asesoramiento Educativo de la UPV/EHU (Proyectos de innovación educativa