Improved post-stroke spontaneous recovery by astrocytic extracellular vesicles.

Spontaneous recovery after a stroke accounts for a significant part of the neurological recovery in patients. However limited, the spontaneous recovery is mechanistically driven by axonal restorative processes for which several molecular cues have been previously described. We report the acceleration of spontaneous recovery in a preclinical model of ischemia/reperfusion in rats via a single intracerebroventricular administration of extracellular vesicles released from primary cortical astrocytes. We used magnetic resonance imaging and confocal and multiphoton microscopy to correlate the structural remodeling of the corpus callosum and striatocortical circuits with neurological performance during 21 days. We also evaluated the functionality of the corpus callosum by repetitive recordings of compound action potentials to show that the recovery facilitated by astrocytic extracellular vesicles was both anatomical and functional. Our data provide compelling evidence that astrocytes can hasten the basal recovery that naturally occurs post-stroke through the release of cellular mediators contained in extracellular vesicles.

Analysis of Habituation Learning in Mealworm Pupae (Tenebrio molitor).

The decline of response as a consequence of repeated stimulation is known as habituation. The goal of the present experiments was extending the knowledge about habituation of abdominal contractions in the pupa of Tenebrio molitor. Both experiments consisted of two phases. During Phase 1, all groups were exposed to a continuous stimulus (light in Experiment 1 and vibration in Experiment 2). At the beginning of this phase, pupae showed a high number of abdominal contractions. However, during the last minute of Phase 1, the number of abdominal contractions was lower. In the next phase, the pupae were divided in different groups to test for response recovery. We found an increase in the abdominal contractions when subjects were exposed to a different stimulus, be it within the same or in a distinct sensory modality. In addition, we also reported response recovery when the pupae were re-exposed to the original stimuli after a resting period. Results indicate that the increase in responding cannot be explained by either sensory adaptation or fatigue. The findings are consistent with the perspective that suggests that habituation plays a major role in the survival of the species, even in non-feeding developmental stages.

Verbal retrieval cues prevent renewal and spontaneous recovery of predictive judgments in university students / Las señales de recuperación verbal evitan la renovación y la recuperación espontánea de juicios predictivos en estudiantes universitarios

Long-term effectiveness is one of the major problems of psychotherapy because successfully eliminated unhealthy behaviors may reappear relatively easily under certain contextual changes. In two experiments, we explored the impact of verbal retrieval cues on renewal and spontaneous recovery in humans. During the first phase, all participants learned a relationship between one cue and one outcome (X-O1). The following phase involved a change in the original relationship (X-O2). Finally, participants were presented with cue X and asked about the relationships with both outcomes. Half of the participants were asked to remember Phase 2, while the other half did not receive any instruction at all. In Experiment 1, testing took place in a different context, while participants in Experiment 2 were tested after two days. The results indicated that remembering Phase 2 eliminated both renewal and spontaneous recovery. Our findings are discussed under the contemporary learning theory. We also mention the probable benefits in therapeutic settings.

Uno de los principales problemas de las psicoterapias es su efectividad a largo plazo porque las conductas poco saludables que se eliminaron exitosamente pueden reaparecer con relativa facilidad bajo ciertos cambios contextuales. En dos experimentos, exploramos el impacto de señales de recuperación verbales en la renovación y en la recuperación espontánea en humanos. En la primera fase, todos los participantes aprendieron una asociación entre una clave y una consecuencia (X-O1). La siguiente fase involucró un cambio en la relación original (X-O2). Finalmente, se les presentó a los participantes la clave X y se les preguntó acerca de las asociaciones con las dos consecuencias. A la mitad de los participantes se les pidió que recordaran la Fase 2, mientras que la otra mitad no recibió ninguna instrucción. En el Experimento 1, la prueba se condujo en un contexto diferente, mientras que en el Experimento 2 la prueba se realizó dos días después. Los resultados indicaron que recordar la Fase 2 eliminó tanto la renovación como la recuperación espontánea. Nuestros hallazgos se discuten bajo la teoría contemporánea del aprendizaje. Asimismo, se mencionan probables beneficios para escenarios terapéuticos

The acquisition, extinction and spontaneous recovery of Pavlovian drug conditioning induced by post-trial dopaminergic stimulation/inhibition.

In contextual drug conditioning, the onset of the drug treatment is contiguous with the contextual cues. Evidence suggests that drug conditioning also can occur if there is a discontinuity between the onset of the drug effect and offset of the contextual cues. Here we examine whether post-trial contextual drug conditioning conforms to several Pavlovian conditioning tenets namely: acquisition, extinction and spontaneous recovery. Six groups of rats received apomorphine (0.05 or 2.0mg/kg) and vehicle immediately or after a 15min delay following a 5min non-drug exposure to an open-field during three successive days (conditioning phase). The extinction phase occurred on days 4-8, in which all post-trial treatments were vehicle injections. After 2days of non-testing, the final test was performed. The results showed that on the first test day, the activity levels of the 6 groups were statistically equivalent. On test day 2, there were marked differences in activity levels selectively between the two immediate post-trial apomorphine treatment groups. The immediate low dose apomorphine group displayed a reduction in activity and the immediate high dose group an increase in activity relative to their day 1 levels. The activity levels of both vehicle groups and both apomorphine delay groups remained equivalent to their day 1 activity levels. On test day 3, the differences in activity levels between the two immediate post-trial apomorphine groups increased but the activity levels of the vehicle groups and the 15min delay post-trial apomorphine groups remained unchanged. In the extinction phase, the conditioned activity differences between the two immediate post-trial apomorphine groups were gradually eliminated. During the final test, the activity differences between the immediate post-trial apomorphine groups were partially restored, indicative of spontaneous recovery. These findings are consistent with several basic elements of Pavlovian conditioning and are supportive of drug induced trace conditioning.

Flexibilidad de la memoria tipo episódica en niños preescolares: tiempo y consecuencia / Flexibility of episodic-like memory in preschool children: Time and consequence

Resumen: La memoria tipo episódica (MTE) implica recordar de manera integrada el qué, el dónde y el cuándo de un evento y es atribuible a animales y humanos, permitiendo recordar y actualizar lo aprendido. Se realizó un experimento para estudiar la actualización y recuerdo integrado en la MTE de niños prescolares. Se compararon dos condiciones (A=B y A>B) que involucraron más de dos fases en las que varió la magnitud para una de las consecuencias. En una primera fase ambas condiciones presentaron la misma información (A+, B+ y C+), mientras que las fases subsecuentes se presentaron diferentes magnitudes de consecuencia (segunda fase: A++++ o A**** de acuerdo a la condición; tercera fase: B++++). Finalmente, la prueba ocurrió 24 h después del entrenamiento y los participantes eligieron entre el contenedor A o B. El qué fue la consecuencia; el dónde, los contenedores, y el cuándo, el orden de cada fase presentada. Los datos sugieren que tras el paso del tiempo los participantes recuerdan de manera integrada el qué, el dónde y el cuándo actualizando el aprendizaje de cada experiencia. Los participantes consideraron la magnitud de la consecuencia obtenida en cada fase, mostrando así la flexibilidad del recuerdo propuesta por la MTE. Los datos son coherentes con las predicciones de la Regla de Ponderación Temporal de Devenport.

Abstract: Episodic-like memory (ELM) involves that animals can remember What, Where and When about an event and it is attributable to animals and humans, this ability permits recall and update learning. One experiment was made for study the update and integrated recall of ELM in preschoolers. We compared two conditions (A = B and A > B) that involve more than two phases with modifying of one magnitude outcome. In the first phase, both conditions had the same information, while next phases had different outcome value in two containers (A or B). Finally, a test was presented after 24 hours: participants chose between A or B container. What, was the outcome subjective value; Where, was the containers and When was the order to each phase. Data suggest that after time pass, participants remember an integrated way about What, Where and When. Even when participants update learning for each experience participants chose according to time and outcome subjective value of each phase and the information retrieval is flexible as happen with ELM. Results are consistent with predictions of Devenport's Temporal Weighting Rule.

Spontaneous recovery from extinction in the infant rat.

Within the Pavlovian conditioning framework, extinction is a procedure in which, after conditioning, the conditioned stimulus (CS) is repeatedly presented without the unconditioned stimulus (US). During this procedure the conditioned response (CR) is gradually attenuated. It has been suggested that extinction during the early stages of ontogeny is a qualitatively different process from extinction in adulthood: during infancy, extinction may result in erasure of the memory, while during adulthood extinction involves new learning. This conclusion was supported by studies showing that renewal, reinstatement or spontaneous recovery procedures were not effective during infancy for recovering the CR once it had been extinguished. These studies used the freezing response as the only behavioral index, although some recent evidence indicates that the absence of freezing after conditioning or after extinction does not necessarily imply a deficit in memory, and that other behavioral indexes may be more sensitive to detecting conditioning effects. The goal of the present study was to analyze extinction in preweanling rats by examining the possibility of the spontaneous recovery of a conditioned fear response, measured through a different set of mutually-exclusive behaviors that constitute an exhaustive ethogram, and including control groups (Experiment 1: US-Only and CS-Only; Experiment 2: US-Only, CS-Only and Unpaired) in order to examine whether non-associative learning may explain quantitative or qualitative changes in the frequency of specific responses during extinction or recovery. Extinction produced changes in the expression of freezing, grooming and exploration, and the clearest evidence of spontaneous recovery came from the analysis of freezing behavior. The pattern of behavior observed during extinction is compatible with theoretical approaches which consider different dynamic behavioral systems, and it also fit in well with a molar approach to the analysis of behavior, which considers that extinction involves a transition from one allocation of time among behaviors to another allocation, rather than a loss of strength in any particular discrete response. These results have implications for the study of extinction during infancy, since they are compatible with the hypothesis that the original memory survives extinction, and highlight the importance of control conditions for detecting this effect during this ontogenetic period.

Evaluation of spontaneous recovery of behavioral and brain injury profiles in zebrafish after hypoxia.

Cerebral hypoxia-ischemia can lead to motor and sensory impairments which can be dependent on the extent of infarcted regions. Since a better understanding of the neurochemical mechanisms involved in this injury is needed, the use of zebrafish as a cerebral hypoxia model has become quite promising because it could improve the knowledge about hypoxia-ischemia. In the current study, we aimed to investigate the spontaneous recovery of brain and behavioral impairments induced by hypoxia in adult zebrafish. Brain injury levels were analyzed by spectrophotometric measurement of mitochondrial dehydrogenase activity by staining with 2,3,5-triphenyltetrazolium chloride, and behavioral profiles were assessed by the open tank test. The induction of hypoxia substantially decreased mitochondrial activity in the brain and impaired behavior. The spontaneous recovery of fish subjected to hypoxia was assessed after 1, 3, 6, 24, and 48h under normoxia. The quantification of brain injury levels showed a significant increase until 24h after hypoxia, but after 48h this effect was completely reversed. Regarding behavioral parameters, we verified that locomotor activity and vertical exploration were impaired by hypoxia and these effects were reversed after 3h under normoxia. Taken together, these results show that zebrafish exhibited transient cerebral and behavioral impairments when submitted to hypoxia, and 1h under normoxic conditions was insufficient to reverse both effects. Therefore, our data help to elucidate the time window of spontaneous recovery in zebrafish after hypoxia and also the behavioral phenotypes involved in this phenomenon.