Molecular Mechanisms in Perirhinal Cortex Selectively Necessary for Discrimination of Overlapping Memories, but Independent of Memory Persistence. Miranda M, Kent BA, Morici JF, Gallo F, Weisstaub NV, Saksida LM, Bussey TJ, Bekinschtein B. 2017

AUTORES Miranda M, Kent BA, Morici JF, Gallo F, Weisstaub NV, Saksida LM, Bussey TJ, Bekinschtein B.
AÑO 2017
VOLUMEN October, 2017
ABSTRACT Successful memory involves not only remembering over time but also keeping memories distinct. The ability to separate similar experiences into distinct memories is a main feature of episodic memory. Discrimination of overlapping representations has been investigated in the dentate gyrus of the hippocampus (DG), but little is known about this process in other regions such as the perirhinal cortex (Prh). We found in male rats that perirhinal brain-derived neurotrophic factor (BDNF) is required for separable storage of overlapping, but not distinct, object representations, which is identical to its role in the DG for spatial representations. Also, activity-regulated cytoskeletal-associated protein (Arc) is required for disambiguation of object memories, as measured by infusion of antisense oligonucleotides. This is the first time Arc has been implicated in the discrimination of objects with overlapping features. Although molecular mechanisms for object memory have been shown previously in Prh, these have been dependent on delay, suggesting a role specifically in memory duration. BDNF and Arc involvement were independent of delay-the same demand for memory persistence was present in all conditions-but only when discrimination of similar objects was required were these mechanisms recruited and necessary. Finally, we show that BDNF and Arc participate in the same pathway during consolidation of overlapping object memories. We provide novel evidence regarding the proteins involved in disambiguation of object memories outside the DG and suggest that, despite the anatomical differences, similar mechanisms underlie this process in the DG and Prh that are engaged depending on the similarity of the stimuli.
RESUMEN Muchas veces se asocia la pérdida de memoria con la imposibilidad de recordar items luego de un intervalo de tiempo. No obstante, la amnesia puede ocurrir porque dos experiencias o ítems fueron similares y al momento de recordarlos, se confunden. El cerebro posee mecanismos para transformar la información proveniente de experiencias similares en memorias diferenciadas que sean menos confundibles al momento de evocarlas. En este trabajo demostramos que los mecanismos moleculares involucrados en el almacenamiento de experiencias similares como memorias diferentes son similares en el dominio espacial y en el de objetos. Estos mecanismos involucran la acción del factor neurotrófico derivado de cerebro (BDNF) tanto en el hipocampo como en la corteza perirrinal, necesarios para el almacenamiento de información espacial y de objetos respectivamente. A pesar de ser dos estructuras anatómicamente muy diferentes, los mecanismos moleculares necesarios para el procesamiento de este tipo de memorias es similar.

Immediate Early Genes, Memory and Psychiatric Disorders: Focus on c-Fos, Egr1 and Arc. Francisco T Gallo, Cynthia Katche, Facundo Morici, Jorge H Medina, Noelia V Weisstaub. 2018

AUTORES Francisco T Gallo, Cynthia Katche, Facundo Morici, Jorge H Medina, Noelia V Weisstaub.
AÑO 2018
JOURNAL Frontiers 
VOLUMEN April 25, 2018
ABSTRACT Many psychiatric disorders, despite their specific characteristics, share deficits in the cognitive domain including executive functions, emotional control and memory. However, memory deficits have been in many cases undervalued compared with other characteristics. The expression of Immediate Early Genes (IEGs) such as, c-fos, Egr1 and arc are selectively and promptly upregulated in learning and memory among neuronal subpopulations in regions associated with these processes. Changes in expression in these genes have been observed in recognition, working and fear related memories across the brain. Despite the enormous amount of data supporting changes in their expression during learning and memory and the importance of those cognitive processes in psychiatric conditions, there are very few studies analyzing the direct implication of the IEGs in mental illnesses. In this review, we discuss the role of some of the most relevant IEGs in relation with memory processes affected in psychiatric conditions.
RESUMEN Mas allá de las diferencias existentes en distintos desordenes psiquiátricos, varios de ellos comparten deficits en el dominio cognitivo, incluyendo deficits de memoria. La expresión de genes como c-Fos, Egr1 y Aarc son selectivamente regulados en procesos de aprendizaje y memoria en regiones y poblaciones neuronales especificas. En esta revision discutimos el rol de algunos de los genes tempranos mas importantes en relación con procesos de memoria afectados en desordenes psiquiátricos.

5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex. Juan Facundo Morici, Magdalena Miranda, Francisco Tomás Gallo, Belén Zanoni, Pedro Bekinschtein, Noelia V. Weisstaub. 2018

AUTORES Juan Facundo Morici, Magdalena Miranda, Francisco Tomás Gallo, Belén Zanoni, Pedro Bekinschtein, Noelia V. Weisstaub.
AÑO 2018
VOLUMEN May 2, 2018
ABSTRACT Context-dependent memories may guide adaptive behavior relaying in previous experience while updating stored information through reconsolidation. Retrieval can be triggered by partial and shared cues. When the cue is presented, the most relevant memory should be updated. In a contextual version of the object recognition task, we examined the effect of medial PFC (mPFC) serotonin 2a receptor (5-HT2aR) blockade during retrieval in reconsolidation of competing objects memories. We found that mPFC 5-HT2aR controls retrieval and reconsolidation of object memories in the perirhinal cortex (PRH), but not in the dorsal hippocampus in rats. Also, reconsolidation of objects memories in PRH required a functional interaction between the ventral hippocampus and the mPFC. Our results indicate that in the presence of conflicting information at retrieval, mPFC 5-HT2aR may facilitate top-down context-guided control over PRH to control the behavioral response and object memory reconsolidation.
RESUMEN Las memorias dependientes de contexto pueden guiar las conductas apoyándose en experiencias pasadas mientras se actualiza la información guardada previamente a través del proceso de reconsolidación. La evocación puede darse por la presentación de calves que son comunes a distintas memorias, en esos casos, la memoria mas relevante debe ser la que sufre el proceso de actualización. En este estudio evaluamos el efecto que el bloqueo del receptor serotoninérgico 5-HT2a en la corteza pre frontal de ratas tiene sobre la reconsolidación de memorias de objetos que compiten al momento de la evocación.

Editorial: Human and Animal Models for Translational Research on Neurodegeneration: Challenges and Opportunities From South America. Ibáñez A, Sedeño L, García AM, Deacon RMJ and Cogram P. 2018

AUTORES Ibáñez A, Sedeño L, García AM, Deacon RMJ and Cogram P.
AÑO 2018
JOURNAL Frontiers Aging Neuroscience
VOLUMEN April 6, 2018
ABSTRACT Facing the alarming growth of dementia and neurodegenerative conditions has become a critical priority across the globe. Although most research on this subject is concentrated in first-world centers, growing efforts in South American countries (SACs) are affording important breakthroughs. This emerging agenda poses not only new challenges for the region, but also new opportunities for the field at large.  This Research Topic engages researchers from the world over, helping to integrate the international community of experts and to establish new challenges and developments for future investigation. We present original research in SACs, including studies assessing the interplay among genetic, neural, and behavioral dimensions of these diseases, as well as articles on vulnerability factors, comparisons of findings from various countries, and works promoting multicenter and collaborative networking. More generally, our Research Topic covers a broad scope of human research approaches (behavioral assessment, neuroimaging, electromagnetic techniques, brain connectivity, peripheral measures), animal methodologies (genetics, epigenetics, proteomics, metabolomics, other molecular biology tools), target species (human and non-human animals, sporadic, and genetic versions), and article types (mainly original research articles, but also case reports, data reports, commentaries, opinions, and reviews), all based on work conducted in SACs. Here, we summarize the main contributions included in the volume. Through this wide-ranging proposal, we hope to introduce a fresh approach to the challenges and opportunities of research on neurodegeneration across these countries, focusing on two overarching levels of evidence (human and animal research), as summarized below.
RESUMEN En esta edición especial, reunimos cientos de expertos regionales que abordan desde múltiples perspectivas los desafíos y oportunidades específicas de Sudamérica para enfrentar la demencia. Los aportes se realizan desde múltiples perspectivas, desde las políticas públicas, la investigación clínica, los modelos preclínicos en animales, y la investigación neurocientífica, entre otros.

Structural Anatomical Investigation of Long-Term Memory Deficit in Behavioral Frontotemporal Dementia. Bertoux M, Flanagan EC, Hobbs M, Ruiz-Tagle A, Delgado C, Miranda M, Ibáñez A, Slachevsky A, Hornberger M. 2018

AUTORES Bertoux M, Flanagan EC, Hobbs M, Ruiz-Tagle A, Delgado C, Miranda M, Ibáñez A, Slachevsky A, Hornberger M.
AÑO 2018
JOURNAL Journal of Alzheimer’s Disease
VOLUMEN March 27, 2018
ABSTRACT Although a growing body of work has shown that behavioral variant frontotemporal dementia (bvFTD) could present with severe amnesia in approximately half of cases, memory assessment is currently the clinical standard to distinguish bvFTD from Alzheimer’s disease (AD). Thus, the concept of “relatively preserved episodic memory” in bvFTD remains the basis of its clinical distinction from AD and a criterion for bvFTD’s diagnosis. This view is supported by the idea that bvFTD is not characterized by genuine amnesia and hippocampal degeneration, by contrast to AD. In this multicenter study, we aimed to investigate the neural correlates of memory performance in bvFTD as assessed by the Free and Cued Selective Reminding Test (FCSRT). Imaging explorations followed a two-step procedure, first relying on a visual rating of atrophy of 35 bvFTD and 34 AD patients’ MRI, contrasted with 29 controls; and then using voxel-based morphometry (VBM) in a subset of bvFTD patients. Results showed that 43% of bvFTD patients presented with a genuine amnesia. Data-driven analysis on visual rating data showed that, in bvFTD, memory recall & storage performances were significantly predicted by atrophy in rostral prefrontal and hippocampal/perihippocampal regions, similar to mild AD. VBM results in bvFTD (pFWE<0.05) showed similar prefrontal and hippocampal regions in addition to striatal and lateral temporal involvement. Our findings showed the involvement of prefrontal as well as medial/lateral temporal atrophy in memory deficits of bvFTD patients. This contradicts the common view that only frontal deficits explain memory impairment in this disease and plead for an updated view on memory dysfunctions in bvFTD.
RESUMEN Aunque se cree que la demencia frontotemporal variante conductual (bvFTD) podría presentarse con amnesia severa la mitad de los casos, la evaluación de memoria es actualmente el estándar clínico para distinguir la enfermedad de Alzheimer de la bvFTD. En este estudio multicéntrico, estudiamos los correlatos neuronales del rendimiento de la memoria en bvFTD. El 43% de los pacientes con bvFTD presentaron amnesia asociada a patrones de atrofia prefrontales, para-, e hipocampales. Los resultados contradicen creencias recientes de que dichos déficits se explicarían solamente por estructuras frontales.

Bilingual memory, to the extreme: Lexical processing in simultaneous interpreters. Santilli M, Vilas M, Mikulan E, Martorell Caro M, Muñoz E, Sedeño L, Ibáñez A, García AM. 2018

AUTORES Santilli M, Vilas M, Mikulan E, Martorell Caro M, Muñoz E, Sedeño L, Ibáñez A, García AM.
AÑO 2018
JOURNAL Bilingualism: Language and Cognition
VOLUMEN April 16, 2018
ABSTRACT This study assessed whether bilingual memory is susceptible to the extreme processing demands of professional simultaneous interpreters (PSIs). Seventeen PSIs and 17 non-interpreter bilinguals completed word production, lexical retrieval, and verbal fluency tasks. PSIs exhibited enhanced fluency in their two languages, and they were faster to translate words in both directions. However, no significant differences emerged in picture naming or word reading. This suggests that lexical enhancements in PSIs are confined to their specifically trained abilities (vocabulary search, interlingual reformulation), with no concomitant changes in other word-processing mechanisms. Importantly, these differences seem to reflect specifically linguistic effects, as both samples were matched for relevant executive skills. Moreover, only word translation performance correlated with the PSIs’ years of interpreting experience. Therefore, despite their tight cooperation, different subcomponents within bilingual memory seem characterized by independent, usage-driven flexibility.
RESUMEN Esta investigación examina cómo la experiencia en interpretación simultánea impacta sobre diversas dimensiones del procesamiento léxico. En comparación con bilingües sin experiencia en interpretación, los profesionales de este rubro mostraron ventajas en fluidez fonológica, fluidez semántica y traducción de palabras. Sin embargo, no exhibieron superioridad en denominación de imágenes o lectura de palabras. Por lo tanto, más allá de su constaten cooperación, diversos mecanismos del sistema bilingüe parecen manifestar patrones de adaptabilidad independientes.

How Argentina is training their mental health residents to face its Silver Tsunami?. Strejilevich, S., Vallejos, F., Bustin, J. 2018

AUTORES  Strejilevich, S., Vallejos, F., Bustin, J.
AÑO 2018
JOURNAL International Psychogeriatrics
VOLUMEN March 21, 2018
ABSTRACT In low- and middle-income countries, there is an increase in the percentage of aging population similar to or greater than that of high-income countries (World Population Ageing 1950–2050, UN, 2001). The emerging health and economical challenges due to these demographic changes will have to be addressed by their health systems. In this context, an adequate training of available human resources in geriatric psychiatry/psychogeriatrics (GP/PG) should be an essential step to meet those challenges.

La ciudad de Buenos Aires presenta una tasa de envejecimiento de su población similar a la de ciudades de países desarrollados. Esto determina un incremento significativo en la incidencia de patologías neuropsiquiátricas en adultos mayores. Dos relevamientos previos realizados en 1994 y 2002 encontraron que los residentes de psiquiatría y psicología de hospitales del sistema público de salud no estaban siendo adecuadamente entrenados para la asistencia de dicha población. Aquí se reportan los resultados de un tercer relevamiento realizado durante 2014. Se realizó una encuesta entre los residentes de salud mental de hospitales dependientes del GCBA. La misma fue administrada con una versión on-line del instrumento utilizado en las encuestas anteriores. Más del 50% de los residentes contestaron la encuesta. Más de dos terceras partes informaron no haber recibido formación de grado en gerontopsiquiatría/ psicogeriatría (GP/PG). Más de la mitad informó haber recibido formación en GP/PG durante la residencia, pero más de dos terceras partes la consideró inadecuada y/o insuficiente. El 24,5% y 38% de los psicólogos y médicos respectivamente informaron asistir por fuera de la residencia a adultos mayores. Más del 40% de los encuestados presentaría prejuicios negativos respecto de la asistencia de esta población. Luego de 20 años de la primera encuesta, persistiría un déficit en la formación de recursos humanos destinados a la asistencia de problemas de salud mental en adultos mayores.

Early bilateral and massive compromise of the frontal lobes. Ibáñez, A., M. Zimerman, L. Sedeño, N. Lori, M. Rapacioli, J. F. Cardona, D. M. A. Suarez, E. Herrera, A. M. García and F. Manes. 2018

AUTORES Ibáñez, A., M. Zimerman, L. Sedeño, N. Lori, M. Rapacioli, J. F. Cardona, D. M. A. Suarez, E. Herrera, A. M. García and F. Manes.
AÑO 2018
JOURNAL NeuroImage: Clinical
VOLUMEN February 26, 2018
ABSTRACT The frontal lobes are one of the most complex brain structures involved in both domain-general and specific functions. The goal of this work was to assess the anatomical and cognitive affectations from a unique case with massive bilateral frontal affectation. We report the case of GC, an eight-year old child with nearly complete affectation of bilateral frontal structures and spared temporal, parietal, occipital, and cerebellar regions. We performed behavioral, neuropsychological, and imaging (MRI, DTI, fMRI) evaluations. Neurological and neuropsychological examinations revealed a mixed pattern of affected (executive control/abstraction capacity) and considerably preserved (consciousness, language, memory, spatial orientation, and socio-emotional) functions. Both structural (DTI) and functional (fMRI) connectivity evidenced abnormal anterior connections of the amygdala and parietal networks. In addition, brain structural connectivity analysis revealed almost complete loss of frontal connections, with atypical temporo-posterior pathways. Similarly, functional connectivity showed an aberrant frontoparietal network and relative preservation of the posterior part of the default mode network and the visual network. We discuss this multilevel pattern of behavioral, structural, and functional connectivity results. With its unique pattern of compromised and preserved structures and functions, this exceptional case offers new constraints and challenges for neurocognitive theories.

Reportamos un caso excepcional de una daño masivo de los lóbulos frontales con preservación temporo-parieto-occipital, reorganización plástica de las conexiones estructurales (DTI) y funcionales (fMRI),  y un desempeño excepcionalmente preservado de algunas funciones cognitivas, afectivas, lingüísticas y sociales. El caso constituye un desafío para nuestro conocimiento de las teorías neurocognitivas  y de plasticidad temprana.

The long-lived Octodon degus as a rodent drug discovery model for Alzheimer’s and other age-related diseases. Hurley MJ, Deacon RMJ, Beyer K, Ioannou E, Ibáñez A, Teeling JL, Cogram P. 2018

AUTORES Hurley MJ, Deacon RMJ, Beyer K, Ioannou E, Ibáñez A, Teeling JL, Cogram P.
AÑO 2018
JOURNAL Pharmacology & Therapeutics
VOLUMEN March 4, 2018
ABSTRACT Alzheimer’s disease (AD) is a multifactorial progressive neurodegenerative disease. Despite decades of research, no disease modifying therapy is available and a change of research objectives and/or development of novel research tools may be required. Much AD research has been based on experimental models using animals with a short lifespan that have been extensively genetically manipulated and do not represent the full spectrum of late-onset AD, which make up the majority of cases. The aetiology of AD is heterogeneous and involves multiple factors associated with the late-onset of the disease like disturbances in brain insulin, oxidative stress, neuroinflammation, metabolic syndrome, retinal degeneration and sleep disturbances which are all progressive abnormalities that could account for many molecular, biochemical and histopathological lesions found in brain from patients dying from AD. This review is based on the long-lived rodent Octodon degus (degu) which is a small diurnal rodent native to South America that can spontaneously develop cognitive decline with concomitant phospho-tau, β-amyloid pathology and neuroinflammation in brain. In addition, the degu can also develop several other conditions like type 2 diabetes, macular and retinal degeneration and atherosclerosis, conditions that are often associated with aging and are often comorbid with AD. Long-lived animals like the degu may provide a more realistic model to study late onset AD.

En este trabajo abordamos el estudio del Octodon degus (degu), un roedor diurno nativo de Sudamérica que desarrolla de forma espontánea demencia a nivel conductual y neurobiológico. Presentamos evidencia que sugiere que el degu podría presentar un modelo farmacológico robusto para la demencia, el deterioro cognitivo y otras enfermedades asociadas al envejecimiento (diabetes tipo 2, degeneración macular y retiniana y la aterosclerosis).

When embodiment breaks down: Language deficits as novel avenues into movement disorders. Adolfo García, Agustín Ibáñez. 2018

AUTORES Adolfo García, Agustín Ibáñez.
AÑO 2018
VOLUMEN February 27, 2018
ABSTRACT If cognition is broadly shaped by an interplay of embodied mechanisms, then cognitive deficits could be profitably reinterpreted as disruptions of embodiment. Despite its simplicity and obviousness, this
straightforward implication has not been systematically assessed in the literature, let alone with a focus on specific target populations featuring systematic disturbances in circumscribed higher-order domains. The present Special Issue seeks to bridge such a gap by delving into the intimate links
between movement disorders and impairments of syntax and action language (namely, verbal expressions alluding to bodily movements).

En este trabajo proponemos reinterpretar diversos déficits lingüísticos en múltiples trastornos motores como alteraciones de mecanismos corporizados. Señalamos las implicancias teóricas de esta concepción para caracterizar la organización cerebral del lenguaje y, más particularmente, para detectar posibles marcadores cognitivos de dichas enfermedades. Así, nuestra propuesta buscar tender un puente entre el marco de la cognición corporizada (embodied cognition) y la neurociencia traslacional.