Learning to Learn: Theta Oscillations Predict New Learning, which Enhances Related Learning and Neurogenesis

Animals in the natural world continuously encounter learning experiences of varying degrees of novelty. New neurons in the hippocampus are especially responsive to learning associations between novel events and more cells survive if a novel and challenging task is learned. One might wonder whether new neurons would be rescued from death upon each new learning experience or whether there is an internal control system that limits the number of cells that are retained as a function of learning. In this experiment, it was hypothesized that learning a task that was similar in content to one already learned previously would not increase cell survival. We further hypothesized that in situations in which the cells are rescued hippocampal theta oscillations (3–12 Hz) would be involved and perhaps necessary for increasing cell survival. Both hypotheses were disproved. Adult male Sprague-Dawley rats were trained on two similar hippocampus-dependent tasks, trace and very-long delay eyeblink conditioning, while recording hippocampal local-field potentials. Cells that were generated after training on the first task were labeled with bromodeoxyuridine and quantified after training on both tasks had ceased. Spontaneous theta activity predicted performance on the first task and the conditioned stimulus induced a theta-band response early in learning the first task. As expected, performance on the first task correlated with performance on the second task. However, theta activity did not increase during training on the second task, even though more cells were present in animals that had learned. Therefore, as long as learning occurs, relatively small changes in the environment are sufficient to increase the number of surviving neurons in the adult hippocampus and they can do so in the absence of an increase in theta activity. In conclusion, these data argue against an upper limit on the number of neurons that can be rescued from death by learning

Early B-cell Factor gene association with multiple sclerosis in the Spanish population

BACKGROUND: The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients. METHODS: The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038. RESULTS: Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03). CONCLUSION: Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them

A Mismatch-Based Model for Memory Reconsolidation and Extinction in Attractor Networks

The processes of memory reconsolidation and extinction have received increasing attention in recent experimental research, as their potential clinical applications begin to be uncovered. A number of studies suggest that amnestic drugs injected after reexposure to a learning context can disrupt either of the two processes, depending on the behavioral protocol employed. Hypothesizing that reconsolidation represents updating of a memory trace in the hippocampus, while extinction represents formation of a new trace, we have built a neural network model in which either simple retrieval, reconsolidation or extinction of a stored attractor can occur upon contextual reexposure, depending on the similarity between the representations of the original learning and reexposure sessions. This is achieved by assuming that independent mechanisms mediate Hebbian-like synaptic strengthening and mismatch-driven labilization of synaptic changes, with protein synthesis inhibition preferentially affecting the former. Our framework provides a unified mechanistic explanation for experimental data showing (a) the effect of reexposure duration on the occurrence of reconsolidation or extinction and (b) the requirement of memory updating during reexposure to drive reconsolidation

Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research

Extinction with multiple excitors

Four conditioned suppression experiments with rats, using an ABC renewal design, investigated the effects of compounding the target conditioned excitor with additional, nontarget conditioned excitors during extinction. Experiment 1 showed stronger extinction, as evidenced by less renewal, when the target excitor was extinguished in compound with a second excitor, relative to when it was extinguished with associatively neutral stimuli. Critically, this deepened extinction effect was attenuated (i.e., more renewal occurred) when a third excitor was added during extinction training. This novel demonstration contradicts the predictions of associative learning models based on total error reduction, but it is explicable in terms of a counteraction effect within the framework of the extended comparator hypothesis. The attenuated deepened extinction effect was replicated in Experiments 2a and 3, which also showed that pretraining consisting of weakening the association between the two additional excitors (Experiments 2a and 2b) or weakening the association between one of the additional excitors and the unconditioned stimulus (Experiment 3) attenuated the counteraction effect, thereby resulting in a decrease in responding to the target excitor. These results suggest that more than simple total error reduction determines responding after extinction