Glucocorticoid-cholinergic interactions in the dorsal striatum in memory consolidation of inhibitory avoidance training

Extensive evidence indicates that glucocorticoid hormones act in a variety of brain regions to enhance the consolidation of memory of emotionally motivated training experiences. We previously reported that corticosterone, the major glucocorticoid in the rat, administered into the dorsal striatum immediately after inhibitory avoidance training dose-dependently enhances memory consolidation of this training. There is also abundant evidence that the intrinsic cholinergic system of the dorsal striatum is importantly involved in memory consolidation of inhibitory avoidance training. However, it is presently unknown whether these two neuromodulatory systems interact within the dorsal striatum in the formation of long-term memory. To address this issue, we first investigated in male Wistar rats whether the muscarinic receptor agonist oxotremorine administered into the dorsal striatum immediately after inhibitory avoidance training enhances 48 h retention of the training. Subsequently, we examined whether an attenuation of glucocorticoid signaling by either a systemic administration of the corticosterone-synthesis inhibitor metyrapone or an intra-striatal infusion of the glucocorticoid receptor (GR) antagonist RU 38486 would block the memory enhancement induced by oxotremorine. Our findings indicate that oxotremorine dose-dependently enhanced 48 h retention latencies, but that the administration of either metyrapone or RU 38486 prevented the memory-enhancing effect of oxotremorine. In the last experiment, corticosterone was infused into the dorsal striatum together with the muscarinic receptor antagonist scopolamine immediately after inhibitory avoidance training. Scopolamine blocked the enhancing effect of corticosterone on 48 h retention performance. These findings indicate that there are mutual interactions between glucocorticoids and the striatal cholinergic system in enhancing the consolidation of memory of inhibitory avoidance training

Extinction procedure induces pruning of dendritic spines in CA1 hippocampal field depending on strength of training in rats

Numerous reports indicate that learning and memory of conditioned responses are accompanied by genesis of dendritic spines in the hippocampus, although there is a conspicuous lack of information regarding spine modifications after behavioral extinction. There is ample evidence that treatments that typically produce amnesia become innocuous when animals are submitted to a procedure of enhanced training. We now report that extinction of inhibitory avoidance (IA), trained with relatively low foot-shock intensities, induces pruning of dendritic spines along the length of the apical dendrites of hippocampal CA1 neurons. When animals are trained with a relatively high foot-shock there is a high resistance to extinction, and pruning in the proximal and medial segments of the apical dendrite are seen, while spine count in the distal dendrite remains normal. These results indicate that pruning is involved in behavioral extinction, while maintenance of spines is a probable mechanism that mediates the protecting effect against amnesic treatments produced by enhanced training

Morris water maze overtraining increases the density of thorny excrescences in the basal dendrites of CA3 pyramidal neurons

The hippocampus plays a fundamental role in spatial learning and memory. Dentate gyrus (DG) granular neurons project mainly to proximal apical dendrites of neurons in the CA3 stratum lucidum and also, to some extent, to the basal dendrites of CA3 pyramidal cells in the stratum oriens. The terminal specializations of DG neurons are the mossy fibers (MF), and these huge axon terminals show expansion in the CA3 stratum oriens after the animals undergo overtraining in the Morris Water Maze task (MWM). However, to our knowledge there are no reports regarding the possible changes in density of post-synaptic targets of these terminals in the basal dendrites of CA3 neurons after overtraining in the MWM. The purpose of this work was to study the density of thorny excrescences (TE) and other dendritic spine types (stubby, thin, and mushroom) in the CA3 stratum oriens in animals overtrained in the MWM for three consecutive days and in animals trained for only one day. Seven days after MWM training, the animals were sacrificed, and their brains removed and processed for rapid Golgi staining to visualize the different types of dendritic protrusions. Our results revealed that the relative quantity of stubby, thin, and mushroom dendritic spines did not change, regardless of amount of training. However, a significant increase in the density of TE was detected in the overtrained animals. These results strongly suggest that spatial water maze overtraining induces an increased density of MF–TE connections, which might be functionally relevant for long-term spatial memory formation.Fil: Gómez Padilla, Eurídice. Universidad Autonoma de Queretaro.; MéxicoFil: Bello Medina, Paola C.. Universidad Nacional Autónoma de México; MéxicoFil: León Jacinto, Uriel. Universidad Nacional Autónoma de México; MéxicoFil: Orta Salazar, Erika. Universidad Nacional Autónoma de México; MéxicoFil: Quirarte, Gina L.. Universidad Nacional Autónoma de México; MéxicoFil: Ramirez Amaya, Victor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Autonoma de Queretaro.; MéxicoFil: Prado Alcalá, Roberto A.. Universidad Nacional Autónoma de México; MéxicoFil: Díaz Cintra, Sofía. Universidad Nacional Autónoma de México; Méxic

Estradiol valerate and alcohol intake: dose-response assessments

BACKGROUND: An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. RESULTS: With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. CONCLUSION: The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries

EL APRENDIZAJE INCREMENTADO PROTEGE A LA MEMORIA CONTRA TRATAMIENTOS AMNÉSICOS

Se hace una descripción somera de las técnicas clásicas utilizadas en el estudiode la neurobiología de la memoria, y de los resultados experimentalesque dieron base a la teoría de la consolidación de la memoria. Asimismo,se describen los experimentos que han dado lugar a una reinterpretaciónde dicha teoría, aplicable a la formación de la memoria de altos niveles deaprendizaje. Los datos derivados de estudios neurobiológicos en los que sehan utilizado diseños que implican aprendizajes mediados por niveles relativamente bajos de reforzamiento o de número de ensayos o de sesionesde entrenamiento, así como los derivados de situaciones de aprendizaje incrementadopueden se explicados en forma sencilla por dos modelos quehemos propuesto: la del procesamiento en serie y la del procesamiento enparalelo, que se discuten en el texto

A consensus protocol for functional connectivity analysis in the rat brain

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience

Efecto terapéutico de la experiencia incrementada: protección contra la amnesia experimental

La administración de drogas que interfieren con la actividad de los sistemas colinérgico y serotoninérgico cerebrales produce deficiencias significativas en la consolidación de la memoria de múltiples tipos de aprendizaje. Sin embargo, cuando los sujetos experimentales son expuestos a situaciones de aprendizaje incrementado, ese mismo tratamiento amnésico deja de ser efectivo, es decir, la consolidación de la memoria se realiza cabalmente. El efecto protector también ha sido demostrado cuando se afecta la actividad sináptica de núcleos cerebrales específicos, tales como el estriado, la amígdala y la substancia nigra. Estos datos se contraponen a la concepción ampliamente aceptada de que la memoria depende de la actividad un grupo selecto de sistemas neuroquímicos y de estructuras cerebrales. Proponemos que la participación de estos sistemas y estructuras no está rígidamente programada, y que depende de la calidad de la experiencia de aprendizaje. Los datos discutidos representan una base objetiva que apoya los informes clínicos de que las experiencias más significativas o más recurrentes son menos vulnerables a procesos amnésicos

Amyloid β Enhances Typical Rodent Behavior While It Impairs Contextual Memory Consolidation

Alzheimer’s disease (AD) is associated with an early hippocampal dysfunction, which is likely induced by an increase in soluble amyloid beta peptide (Aβ). This hippocampal failure contributes to the initial memory deficits observed both in patients and in AD animal models and possibly to the deterioration in activities of daily living (ADL). One typical rodent behavior that has been proposed as a hippocampus-dependent assessment model of ADL in mice and rats is burrowing. Despite the fact that AD transgenic mice show some evidence of reduced burrowing, it has not been yet determined whether or not Aβ can affect this typical rodent behavior and whether this alteration correlates with the well-known Aβ-induced memory impairment. Thus, the purpose of this study was to test whether or not Aβ affects burrowing while inducing hippocampus-dependent memory impairment. Surprisingly, our results show that intrahippocampal application of Aβ increases burrowing while inducing memory impairment. We consider that this Aβ-induced increase in burrowing might be associated with a mild anxiety state, which was revealed by increased freezing behavior in the open field, and conclude that Aβ-induced hippocampal dysfunction is reflected in the impairment of ADL and memory, through mechanisms yet to be determined