Análisis comparado del aprendizaje aversivo en anfibios

El presente artículo desarrolla con un enfoque comparado una revisión completa y actualizada de los estudios de aprendizaje aversivo en anfibios. La mayoría de ellos utilizaron como estímulo aversivo descargas eléctricas, obteniéndose resultados inconsistentes o negativos. Las investigaciones más recientes mostraron que otra clase de estímulos (soluciones salinas de alta concentración, o aumento de la temperatura del agua) han resultado ser más eficientes para producir modificaciones estables en el comportamiento. Se analizan también algunos aspectos neurofisiológicos relacionados con el aprendizaje aversivo y los miedos aprendidos. Si bien se cuenta con datos comparativos de estudios neurofisiológicos en peces, aún no existen referencias con información funcional sobre las bases neurales del aprendizaje aversivo en anfibios. Sin embargo, sí se conoce en anfibios las regiones cerebrales homólogas a las estructuras que en mamíferos mostraron estar implicadas con dicho aprendizaje (especialmente la amígdala), abriendo así el camino para abordar en el futuro el estudio de esta cuestión.Comparative analysis of aversive learning in amphibians: This article develops with a comparative approach a comprehensive and updated review of studies of aversive learning in amphibians. Most of them used electric shock as aversive stimulus, resulting in inconsistent or negative results. Recent research showed that another class of stimuli (saline solutions highly concentrated or warm water) has been more efficient to produce steady changes in behavior. Some neurophysiological aspects of aversive and fear learning are also discussed. While comparative data from neurophysiological studies in fish is available, there are no references on functional information on the neural basis of aversive learning in amphibians. However, it is known in amphibian homologous brain areas to the mammalian structures shown to be involved with such learning (especially the amygdala), opening the way to address the study of this question in the future.Fil: Puddington, Martin Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biologia y Medicina Experimental (i); Argentina; Universidad de Buenos Aires. Facultad de Psicologia; Argentina;Fil: Muzio, Ruben Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biologia y Medicina Experimental (i); Argentina; Universidad de Buenos Aires. Facultad de Psicologia; Argentina

The Role of β7 Integrins in CD8 T Cell Trafficking During an Antiviral Immune Response

The requirement of β7 integrins for lymphocyte migration was examined during an ongoing immune response in vivo. Transgenic mice (OT-I) expressing an ovalbumin-specific major histocompatibility complex class I–restricted T cell receptor for antigen were rendered deficient in expression of all β7 integrins or only the αEβ7 integrin. To quantitate the relative use of β7 integrins in migration in vivo, equal numbers of OT-I and OT-I-β7−/− or OT-I-αE−/− lymph node (LN) cells were adoptively transferred to normal mice. Although OT-I-β7−/− LN cells migrated to mesenteric LN and peripheral LN as well as wild-type cells, β7 integrins were required for naive CD8 T cell and B cell migration to Peyer's patch. After infection with a recombinant virus (vesicular stomatitis virus) encoding ovalbumin, β7 integrins became critical for migration of activated CD8 T cells to the mesenteric LN and Peyer's patch. Naive CD8 T cells did not enter the lamina propria or the intestinal epithelium, and the majority of migration of activated CD8 T cells to the small and large intestinal mucosa, including the epithelium, was β7 integrin–mediated. The αEβ7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of αEβ7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also αEβ7 independent

Análisis comparado del aprendizaje aversivo. Estudios en anfibios

This article develops with a comparative approach a comprehensive and updated review of studies of aversive learning in amphibians. Most of them used electric shock as aversive stimulus, resulting in inconsistent or negative results. Recent research showed that another class of stimuli (saline solutions highly concentrated or warm water) has been more efficient to produce steady changes in behavior. Some neurophysiological aspects of aversive and fear learning are also discussed. While comparative data from neurophysiological studies in fish is available, there are no references on functional information on the neural basis of aversive learning in amphibians. However, it is known in amphibian homologous brain areas to the mammalian structures shown to be involved with such learning (especially the amygdala), opening the way to address the study of this question in the future.El presente artículo desarrolla con un enfoque comparado una revisión completa y actualizada de los estudios de aprendizaje aversivo en anfibios. La mayoría de ellos utilizaron como estímulo aversivo descargas eléctricas, obteniéndose resultados inconsistentes o negativos. Las investigaciones más recientes mostraron que otra clase de estímulos (soluciones salinas de alta concentración, o aumento de la temperatura del agua) han resultado ser más eficientes para producir modificaciones estables en el comportamiento. Se analizan también algunos aspectos neurofisiológicos relacionados con el aprendizaje aversivo y los miedos aprendidos. Si bien se cuenta con datos comparativos de estudios neurofisiológicos en peces, aún no existen referencias con información funcional sobre las bases neurales del aprendizaje aversivo en anfibios. Sin embargo, sí se conoce en anfibios las regiones cerebrales homólogas a las estructuras que en mamíferos mostraron estar implicadas con dicho aprendizaje (especialmente la amígdala), abriendo así el camino para abordar en el futuro el estudio de esta cuestión

Avidity maturation of memory CD8 T cells is limited by self-antigen expression

Immune tolerance to self-antigens is a complex process that utilizes multiple mechanisms working in concert to maintain homeostasis and prevent autoimmunity. We developed a system that revealed a population of self-specific CD8 T cells within the endogenous T cell repertoire. Immunization of ovalbumin (OVA)-expressing transgenic mice with recombinant viruses expressing OVA-peptide variants induced self-reactive T cells in vivo that matured into memory T cells able to respond to secondary infection. However, whereas the avidity of memory cells in normal mice increased dramatically with repeated immunizations, avidity maturation was limited for self-specific CD8 T cells. Despite decreased avidity, such memory cells afforded protection against infection, but did not induce overt autoimmunity. Further, up-regulation of self-antigen expression in dendritic cells using an inducible system promoted programmed death-1 expression, but not clonal expansion of preexisting memory cells. Thus, the self-reactive T cell repertoire is controlled by overlapping mechanisms influenced by antigen dose

IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring

<p>Abstract</p> <p>Background</p> <p>The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood. Using an established murine model of asthma, we demonstrated previously that resistance to allergic airway disease transmitted from allergic mothers to breastfed offspring requires maternal B cell-derived factors.</p> <p>Objective</p> <p>The aim of this study was to investigate the role of offspring neonatal Fc receptor for IgG uptake by intestinal epithelial cells (FcRn) in this breast milk transferred protection from allergy.</p> <p>Methods</p> <p>Allergic airway disease was induced during pregnancy in C57BL/6 female mice. These allergic mothers foster nursed naive FcRn^+/-or FcRn^-/-progeny born to FcRn^+/-females that were mated to C57BL/6J-FcRn^-/-male mice. In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG₁, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract. Using this model, we were able to investigate how breast milk IgG affected offspring responses to allergic sensitization.</p> <p>Results</p> <p>Levels of maternal antibodies absorbed from the breast milk of allergic foster mothers were determined in weanling FcRn-sufficient or -deficient mice. Maternal transmission of allergen-specific IgG₁to breastfed FcRn^-/-offspring was at levels 10³-10⁴lower than observed in FcRn^+/-or FcRn^+/+mice. Five weeks after weaning, when offspring were 8 wk old, mice were sensitized and challenged to evaluate their susceptibility to develop allergic airway disease. Protection, indicated by reduced parameters of disease (allergen-specific IgE in serum, eosinophilic inflammation in the airways and lung) were evident in FcRn-sufficient mice nursed as neonates by allergic mothers. In contrast, FcRn-deficient mice breastfed by the same mothers acquired limited, if any, protection from development of allergen-specific IgE and associated pathology.</p> <p>Conclusions</p> <p>FcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG₁sufficient to inhibit allergic sensitization in this model.</p

Experimental model in amphibians: unidimensionality of the processing of appetitive and aversive stimuli in associative learning

En el condicionamiento clásico,un animal es expuesto a un estímulo neutro (estímulo condicionado) seguido deun estímulo apetitivo o aversivo (estímulo incondicionado). Sucesivasrepeticiones de esta asociación generan una respuesta frente al estímulo neutrocomo si se tratara del estímulo incondicionado, fenómeno ampliamente exploradoen distintas clases zoológicas (desde invertebrados hasta humanos). En general,los estímulos incondicionados apetitivos y aversivos corresponden a víassensoriales diferentes (típicamente el estímulo utilizado como apetitivo escomida, excitando mayormente receptores gustativos; mientras que como estímuloaversivo se usa una descarga eléctrica, actuando sobre las vías táctiles ynociceptivas). Los estudios en anfibios, en particular el sapo terrestre,reproducen en buena medida los hallazgos en otras especies animales, perotienen características que los hacen únicos al poseer receptores a electrolitosen su piel que intervienen en la regulación del balance hidrosalino corporal.Un sapo expuesto a una solución salina levemente hipertónica (concentraciónmenor a 250 mM NaCl), gana peso y exhibe conductas de aproximación. Alcontrario, si la solución salina es altamente hipertónica (concentraciónsuperior a 400 mM NaCl), pierde peso y exhibe conductas de escape. Así, unmismo estímulo (una solución salina de NaCl), actúa como estímulo apetitivo oaversivo dependiendo de su concentración, característica que denominamosunidimensionalidad de los estímulos motivacionales. El presente trabajodescribe los procedimientos y revisa los resultados de estudios de aprendizajeasociativo en sapos, resaltando el uso de este modelo experimental para elanálisis de los mecanismos neurales implicados en el procesamiento de señalesambientales apetitivas y aversivas.In classical conditioning, an animal is exposed to a neutral stimulus (conditioned stimulus) followed by an appetitive or aversive stimulus (unconditioned stimulus). With successive repetitions of this association, the animal will respond to the neutral stimulus as if it were the unconditioned stimulus. is phenomenon has been widely explored in different zoological classes, covering animal species ranging from mollusks to humans. In most cases, appetitive and aversive unconditioned stimuli correspond to different sensory pathways. For example, the appetitive stimulus typically used is food and the typical aversive stimulus is electric shock. us one type of stimulus will excite the receptors related to the sense of taste, while the other type will do so mostly on the tactile and nociceptive pathways. Studies on amphibians, particularly the terrestrial toad, reproduce to a large extent the findings in other animal species, but they have characteristics that make them unique by having electrolyte receptors in their skin that are involved in the regulation of their body's hydrosaline balance. A toad exposed to a slightly hypertonic saline solution (concentration less than 250 mM NaCl) gains weight and exhibits approximation behaviors. Whereas if it takes contact with a highly hypertonic saline solution (concentration higher than 400 mM NaCl), it loses weight and exhibits escape behaviors. us, the same stimulus (a saline solution of NaCl), can act as an appetitive or aversive stimulus depending on its concentration. is particularity has been called unidimensionality of motivational stimuli. In the present work we describe the procedures and review the results of associative learning studies in toads, highlighting the use of this experimental model for the study of the possible neural mechanisms involved in the processing of appetitive and aversive environmental signals.Fil: Muzio, Ruben Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Psicología; ArgentinaFil: Puddington, Martin Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Psicología; Argentin

Oral Infection Drives a Distinct Population of Intestinal Resident Memory CD8+ T Cells with Enhanced Protective Function

SummaryThe intestinal mucosa promotes T cell responses that might be beneficial for effective mucosal vaccines. However, intestinal resident memory T (Trm) cell formation and function are poorly understood. We found that oral infection with Listeria monocytogenes induced a robust intestinal CD8 T cell response and blocking effector T cell migration showed that intestinal Trm cells were critical for secondary protection. Intestinal effector CD8 T cells were predominately composed of memory precursor effector cells (MPECs) that rapidly upregulated CD103, which was needed for T cell accumulation in the intestinal epithelium. CD103 expression, rapid MPEC formation, and maintenance in intestinal tissues were dependent on T cell intrinsic transforming growth factor β signals. Moreover, intestinal Trm cells generated after intranasal or intravenous infection were less robust and phenotypically distinct from Trm cells generated after oral infection, demonstrating the critical contribution of infection route for directing the generation of protective intestinal Trm cells

Retenção e extinção diferida de uma resposta instrumental no sapo Rhinella arenarum: efeitos do overtraining

Amphibians and mammals share common basic mechanisms for associative learning. However, it has been observed that certain reinforcement paradigms produce opposite results. For example, increasing the number of reinforced trials during acquisition (Overtraining) improves mammals’ extinction and impairs amphibians’. The present study evaluates in toads, the effect of overtraining on response retention after 8 days without training. Two groups of animals were trained in a runway receiving 5 or 15 acquisition trials respectively. After acquisition ended, each group remained 8 days without training and then received 8 extinction trials. Differences were not observed in the spontaneous decay rate. Since it had previously observed that using the same parameters in the acquisition leads to a faster extinction in the 5 days group, it is consider the idea that mechanisms underlying extinction and spontaneous decay differs.Los anfibios y los mamíferos comparten mecanismos básicos comunes para el aprendizaje asociativo. Sin embargo, se observa que algunos paradigmas de refuerzo producen resultados opuestos. Por ejemplo, el aumento del número de ensayos reforzados durante la adquisición (sobreentrenamiento) acelera la extinción en mamíferos, pero la retarda en anfibios. Este estudio evalúa en sapos los efectos del sobreentrenamiento sobre la retención de una respuesta luego de 8 días sin entrenamiento y la subsecuente extinción diferida. Se entrenaron dos grupos de animales en un corredor recto durante 5 o 15 ensayos de adquisición, un ensayo por día. La adquisición fue seguida por un intervalo de retención de 8 días sin entrenamiento, y luego por 8 ensayos de extinción. No se observaron diferencias en la tasa de decaimiento durante el primer ensayo de extinción oen la tasa de extinción diferida. Dado que los mismos parámetros de entrenamiento habían permitido observar un claro efecto de sobreentrenamiento en la extincióninmediata, se propone que los mecanismos que regulan la extinción instrumental son diferentes de los que actúan en el decaimiento espontáneo de la respuesta.Palabras clave: aprendizaje instrumental, anfibios, sobreentrenamiento, extinción.Os anfíbios e os mamíferos compartilham mecanismos básicos comuns para a aprendizagem associativa. No entanto, observa-se que alguns paradigmas de reforço produzem resultados opostos. Por exemplo, o aumento do número de ensaios reforçados durante a aquisição (overtraining) acelera a extinção em mamíferos, mas a retarda em anfíbios. Este estudo avalia em sapos os efeitos do overtraining sobre a retenção de uma resposta após 8 dias sem treinamento e a subsequente extinção diferida. Treinaram-se dois grupos de animais em umcorredor reto durante 5 ou 15 ensaios de aquisição, um ensaio por dia. A aquisição foi seguida por um intervalo de retenção de 8 dias sem treinamento, e depois por 8  ensaios de extinção. Não se observaram diferenças na taxa de decaimento durante o primeiro ensaio de extinção ou na taxa de extinção diferida. Devido a que os mesmos parâmetros de treinamento tinham permitido observar um claro efeito de overtraining na extinção imediata, se propõe que os mecanismos que regulam a extinção instrumental são  diferentes dos que atuam no decaimento espontâneo da resposta.Palavras-chave: aprendizagem instrumental, anfibios, overtraining, extinção