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The amacrine neurons in the mammalian retina comprise a large variety of cell types with distinct properties and functions that serve to integrate and modulate signals presented to output neurons. The majority of them use either glycine or GABA as inhibitory neurotransmitters and express the glycine transporter 1 (GlyT1) or glutamic acid decarboxylase (GAD67) and GABA transporters (GAT1 and GAT3), as a glycinergic or GABAergic marker respectively. We report here a novel subpopulation of amacrine neurons expressing both, GABAergic and glycinergic markers, in retinas from wild-type C57BL/6J mice and two transgenic lines. In retinal sections from the transgenic line expressing eGFP under the control of the glycine transporter 2, eGFP expression was exclusively found in cell bodies and dendrites of inhibitory amacrine neurons, identified for their immunoreactivity to syntaxin 1A. All of the glycinergic and a large portion of the GABAergic amacrine neurons contained eGFP; of these, 8-10% of GlyT1 positive neurons were also labeled either with GAD67, GAT1 or GAT3. These findings were confirmed in retinas from a wild-type and a mouse line expressing eGFP under the GAD67 promoter and two different anti-GlyT1 antibodies, showing the presence of a subpopulation with a dual phenotype. Moreover, eGFP-positive dendrites on both mouse lines were found juxtaposed to GlyR subunits and the scaffold protein gephyrin in several areas of the inner plexiform layer, demonstrating the glycinergic character of these neurons. This dual phenotype was also demonstrated in primary retina cultures, in which isolated neurons were positive for GlyT1 and GAD67 or GAT1/3. Altogether, these data provide compelling evidence of a subpopulation of dual inhibitory, glycinergic/GABAergic amacrine neurons. The co-release of both neurotransmitters may serve to strengthen the inhibition on ganglion cells under synaptic hyperexcitability.

In the vertebrate nervous system, glycinergic neurotransmission is tightly regulated by the action of the glycine transporters 1 and 2 (GlyT1 and GlyT2). Unlike GlyT1, the GlyT2 is characterized by the presence of a cytosolic 201 amino acids N-terminal tail of unknown function. In the present study, we stably expressed a set of GlyT2 N-terminal deletion mutants and characterized the effect on uptake, trafficking and PKC-dependent post-translational modifications. The deletion of the first 43, 109 or 157 amino acids did not affect the trafficking and maturation of GlyT2. Similarly, a chimeric protein replacing GlyT2 N-terminus by the corresponding tail of GlyT1b or deletion of the entire N-terminus domain (Δ201), was able to reach the plasma membrane but showed faster turnover compared to the wild-type. All of these mutant proteins appeared as a mature, glycosylated transporter and a lower protein band corresponding to the non-glycosylated transporter. Interestingly, glycine uptake and PKC-mediated endocytosis and further reduction of transport were not affected by the deletions of 43–157 amino acids. Moreover, the analysis of PKC-dependent post-translational modifications for the mutants demonstrated that GlyT2 transporter ubiquitination was not affected; however, PKC-dependent transporter phosphorylation was completely abolished in the deletions of 157 and 201 amino acids. Altogether, these results suggest that the GlyT2 N-terminus does not directly participate in the modulation of transport properties but it could be relevant for scaffold formation and retention at active zones or communication to an intracellular signaling pathway.

Throughout The Modern Age the hidalguía suffered a serious conceptual evolution. At the end of the Ancien Régime the loss of the medieval features and its conversion to a legal reality regulated by the State were one of the most prominent characteristics. In this research we analyze the transformational factors of the nobility in a legal statute closely regulated which was at the service of the absolutist monarchy. In order to analyze it we have chosen processes of hidalguía initiated in the Royal Chancelleries as the core idea of the research, demonstrating that, their utility was not only as instruments used to supervise the access to nobility, but, what is more, they are a form of the new identity adopted by the Bourbon nobility; the subordinate state which depends on the crown., A lo largo de la Edad Moderna la hidalguía experimentaría una significativa evolución conceptual. A finales del Antiguo Régimen, la pérdida de sus rasgos medievales y su conversión en una realidad jurídica regulada por el Estado serían algunas de sus características más destacadas. En este trabajo analizaremos los factores de la transformación de la hidalguía en un estatuto jurídico estrechamente fiscalizado y al servicio de la monarquía absolutista. Para ello, hemos elegido como eje de la investigación los procesos de hidalguía incoados ante las Reales Chancillerías que, como aquí demostraremos, no solo sirvieron como instrumentos para supervisar el acceso a la hidalguía sino que además son una plasmación de la nueva identidad adoptada por la nobleza borbónica: la de un estamento subordinado y dependiente de la Corona.

La compleja morfología del estamento nobiliario de la américa española ha supuesto, en cierta medida, que el estudio de la mentalidad nobiliaria se haya limitado a la nobleza titulada. e n el presente trabajo resaltar la importancia de la nobleza no titulada o hidalguía en américa a finales del antiguo r égimen. c on esta finalidad hemos utilizado como eje de la investigación los procesos de hidalguía incoados ante la real chancillería de valladolid por parte de americanos y peninsulares con residencia en el p erú. e l análisis de esta fuente judicial revela la influencia de un “imperativo nobiliario”, es decir, la necesidad de legitimar las aspiraciones sociales mediante la acreditación de la hidalguía. l as razones de los pretendientes para solicitar el reconocimiento de su hidalguía y el uso de estos despachos en beneficio de su estatus social nos permite comprender la trascendencia de estas solicitudes de la sociedad del antiguo régimen., The difficult morphology of the noble estate in america has, to a certain point, meant that the study of the noble mentality is limited to the titled nobility. this article highlights the impor - tance of the untitled nobility or hidalguía in america at the end of the ancien r égime. For this purpose the core idea of this study is based on the evidence of hidalguía of the r eal c hancillería of valladolid regarding the americans and peninsular dwellers in p erú. the analysis of this judicial source reveals the presence of a “noble imperative,” that is, the necessity to legalize and check the social aspirations through the recognition of the hidalguía. the reasons to apply for the recognition of the hidalguía and the use of these titles to benefit their social status allow us to understand the importance of these requests of the ancien régime.

La identidad colectiva de la nobleza española era una realidad compleja que agrupaba diferentes conceptos (nobleza e hidalguía, limpieza de sangre y de oficios). A finales de la Edad Moderna el deseo de demostrar este “buen origen” llevaría a muchos de estos nobles a solicitar pruebas de hidalguía. A partir del estudio de estos documentos nos proponemos en este trabajo reconocer esta mentalidad nobiliaria en la América española, de origen netamente castellana pero dotada de sus propias peculiaridades regionales

Textos de comunicaciones defendidas en la XI Reunión Científica de la Fundación Española de Historia Moderna, previa evaluación ciega por pares., Esta investigación se realiza con el apoyo de una Beca FPI de la Junta de Castilla y León

Durante la Edad Moderna y especialmente durante el siglo XVIII, la hidalguía, como condición privilegiada, fue ambicionada por gran parte de la población. Aunque su acceso estaba cerrado a la mayor parte de la población pronto se diseñaron procedimientos para burlar este obstáculo como el fraude y la manipulación de las pruebas de nobleza. En el espacio local esta problemática se centra en las intrusiones en el estado noble, una cuestión que no solo se limitará al enfrentamiento entre plebeyos e hidalgos sino que también afectará a los intereses del Estado.