The Role of Neurosciences in Education... and Vice Versa

One of the key questions in education is how the learning process in the classroom takes place and how different environmental and individual circumstances (attention, motivation, nutrition, stimulus presentation, etc.) can enhance the child’s capabilities to learn and to remember. These and other cognitive skills are shaped as a consequence of the infant brain activity. Therefore, the provision of any information (included that obtained using animal models) relating to how the brain builds up learning and memory should be of high adaptive value. It is considered that an effort is needed to establish both a common language between education and neuroscience and a clear framework for exchanging questions and data

Associative learning and CA3–CA1 synaptic plasticity are impaired in D1r Null, Drd1a–/– mice and in hippocampal siRNA silenced Drd1a mice

Associative learning depends on multiple cortical and subcortical structures, including striatum, hippocampus, and amygdala. Both glutamatergic and dopaminergic neurotransmitter systems have been implicated in learning and memory consolidation. While the role of glutamate is well established, the role of dopamine and its receptors in these processes is less clear. In this study, we used two models of dopamine D₁ receptor (D₁R, Drd1a) loss, D₁R knock-out mice (Drd1a–/–) and mice with intrahippocampal injections of Drd1a-siRNA (small interfering RNA), to study the role of D₁R in different models of learning, hippocampal long-term potentiation (LTP) and associated gene expression. D₁R loss markedly reduced spatial learning, fear learning, and classical conditioning of the eyelid response, as well as the associated activity-dependent synaptic plasticity in the hippocampal CA1–CA3 synapse. These results provide the first experimental demonstration that D₁R is required for trace eyeblink conditioning and associated changes in synaptic strength in hippocampus of behaving mice. Drd1a-siRNA mice were indistinguishable from Drd1a–/– mice in all experiments, indicating that hippocampal knockdown was as effective as global inactivation and that the observed effects are caused by loss of D₁R and not by indirect developmental effects of Drd1a–/–. Finally, in vivo LTP and LTP-induced expression of Egr1 in the hippocampus were significantly reduced in Drd1a–/– and Drd1a-siRNA, indicating an important role for D₁R in these processes. Our data reveal a functional relationship between acquisition of associative learning, increase in synaptic strength at the CA3–CA1 synapse, and Egr1 induction in the hippocampus by demonstrating that all three are dramatically impaired when D₁R is eliminated or reduced

R-ras1 and r-ras2 are essential for oligodendrocyte differentiation and survival for correct myelination in the central nervous system

Rapid and effective neural transmission of information requires correct axonal myelination. Modifications in myelination alter axonal capacity to transmit electric impulses and enable pathological conditions. In the CNS, oligodendrocytes (OLs) myelinate axons, a complex process involving various cellular interactions. However, we know little about the mechanisms that orchestrate correct myelination. Here, we demonstrate that OLs express R-Ras1 and R-Ras2. Using female and male mutant mice to delete these proteins, we found that activation of the PI3K/Akt and Erk1/2-MAPK pathways was weaker in mice lacking one or both of these GTPases, suggesting that both proteins coordinate the activity of these two pathways. Loss of R-Ras1 and/or R-Ras2 diminishes the number of OLs in major myelinated CNS tracts and increases the proportion of immature OLs. In R-Ras1-/-and R-Ras2-/--null mice, OLs show aberrant morphologies and fail to differentiate correctly into myelin-forming phenotypes. The smaller OL population and abnormal OL maturation induce severe hypomyelination, with shorter nodes of Ranvier in R-Ras1-/-and/or R-Ras2-/-mice. These defects explain the slower conduction velocity of myelinated axons that we observed in the absence of R-Ras1 and R-Ras2. Together, these results suggest that R-Ras1 and R-Ras2 are upstream elements that regulate the survival and differentiation of progenitors into OLs through the PI3K/Akt and Erk1/2-MAPK pathways for proper myelination.This work was supported by the Spanish Ministry of Economy and Competitiveness (BFU2015-64829-S and SAF2012-31279) to B.C. and (SAF2015-70368-R) to F.W

Interval Timing and Time-Based Decision Making

International audienceThe importance of time perception and timed performance is revealed in everyday activities from the sleep–wake cycle to verbal communication, playing, and appreciating music, the exquisite temporal control of both voluntary and involuntary behavior, and choice. With regard to the last point, making decisions is heavily influenced by the duration of the various options, the duration of the expected delays for receiving the options, and the time constraints for making a choice. Recent advances suggest that the brain represents time in a distributed manner and reflects time as a result of temporal changes in network states and/or by the coincidence detection of the phase of different neural populations. Moreover, the oscillatory properties of neural circuits can be shown to influence the acquisition of conditioned responding and the timing of motor responses. This Research Topic on “Interval Timing and Time-Based Decision Making” emerged from a symposium sponsored by the European COST-Action on Time In MEntaL activity: theoretical, behavioral, bioimaging, and clinical perspectives (TIMELY) that was a satellite of the European Brain and Behaviour Society meeting held in Seville, Spain (September 9, 2011). The focus of that TIMELY symposium was on “Neurobiology of Time Perception: From Normality to Dysfunction” and was organized by Valérie Doyère, Argiro Vatakis, and Elzbieta Szelag

El cerebro como máquina para aprender, recordar y olvidar

The brain is the organ responsible for two noticeable abilities, to think and to behave, the two of which are dependent on the capability to learn and to store the acquired information. The evident advances of the Neurosciences in the past few years has allowed the discovery of the mechanism underlying those processes, but many other aspects still wait for a discovery. Reasonable information is available on neuronal architecture and neuronal connecting processes, as well as on cerebral structures related with the generation and storage of the different types of memory. These findings have opened a path for the developing of drugs related to those neural processes. On the other hand, science fiction and media influences have potentiated the survival of several legends regarding the nervous system extraordinary capabilities: from considering the brain as a computer to accepting that it is a plastic structure with unlimited capabilities.El cerebro es el órgano responsable de dos grandes habilidades, pensar y actuar, las cuales requieren de la capacidad de aprender y de recordar la información adquirida. El gran avance de las Neurociencias en los últimos años ha permitido conocer algunos de los mecanismos que subyacen a estos procesos, pero quedan aún muchos aspectos por descubrir. Se conoce la estructura neuronal y muchos de los mecanismos de comunicación entre neuronas y se han identificado algunas estructuras relacionadas con la elaboración y almacenamiento de los diferentes tipos de memoria. Esto ha animado al desarrollo de fármacos que puedan incidir positivamente sobre estos procesos. La ciencia ficción por un lado, y la presión mediática por el otro, han hecho que perduren algunas leyendas acerca de las extraordinarias capacidades del sistema nervioso: desde aceptar que el cerebro es como un ordenador a pensar que es de una estructura plástica con capacidades prácticamente ilimitadas

Differing Presynaptic Contributions to LTP and Associative Learning in Behaving Mice

The hippocampal CA3-CA1 synapse is an excellent experimental model for studying the interactions between short- and long-term plastic changes taking place following high-frequency stimulation (HFS) of Schaffer collaterals and during the acquisition and extinction of a classical eyeblink conditioning in behaving mice. Input/output curves and a full-range paired-pulse study enabled determining the optimal intensities and inter-stimulus intervals for evoking paired-pulse facilitation (PPF) or depression (PPD) at the CA3-CA1 synapse. Long-term potentiation (LTP) induced by HFS lasted ≈10 days. HFS-induced LTP evoked an initial depression of basal PPF. Recovery of PPF baseline values was a steady and progressive process lasting ≈20 days, i.e., longer than the total duration of the LTP. In a subsequent series of experiments, we checked whether PPF was affected similarly during activity-dependent synaptic changes. Animals were conditioned using a trace paradigm, with a tone as a conditioned stimulus (CS) and an electrical shock to the trigeminal nerve as an unconditioned stimulus (US). A pair of pulses (40 ms interval) was presented to the Schaffer collateral-commissural pathway to evoke field EPSPs (fEPSPs) during the CS-US interval. Basal PPF decreased steadily across conditioning sessions (i.e., in the opposite direction to that during LTP), reaching a minimum value during the 10th conditioning session. Thus, LTP and classical eyeblink conditioning share some presynaptic mechanisms, but with an opposite evolution. Furthermore, PPF and PPD might play a homeostatic role during long-term plastic changes at the CA3-CA1 synapse

BASES FISIOLÓGICAS DEL APRENDIZAJE ASOCIATIVO

El condicionamiento clásico del reflejo corneal es un modelo muy utilizado en el estudio de los procesos de aprendizaje y memoria. Nuestro grupo de investigación ha estudiado las características cinéticas de las respuestas palpebrales reflejas, voluntarias, emocionales y aprendidas, así como la fisiología de las motoneuronas que inervan el músculo orbicularis oculi, encargado de realizar dichos movimientos. Las motoneuronas faciales codifican la velocidad de cierre de los párpados durante respuestas reflejas y su posición durante respuestas aprendidas. Esta diferencia indica un diferente procesamiento (y/u origen) de ambas órdenes motoras. Tanto la corteza paravermal como el núcleo interpósito posterior del cerebelo están relacionados con los movimientos palpebrales reflejos y aprendidos, contribuyendo a su correcta realización, pero no a su aprendizaje. A su vez, el hipocampo interviene en la determinación del valor predictivo del estímulo condicionado, durante condicionamientos de tipo pavloviano

Timing and Causality in the Generation of Learned Eyelid Responses

The cerebellum-red nucleus-facial motoneuron (Mn) pathway has been reported as being involved in the proper timing of classically conditioned eyelid responses. This special type of associative learning serves as a model of event timing for studying the role of the cerebellum in dynamic motor control. Here, we have re-analyzed the firing activities of cerebellar posterior interpositus (IP) neurons and orbicularis oculi (OO) Mns in alert behaving cats during classical eyeblink conditioning, using a delay paradigm. The aim was to revisit the hypothesis that the IP neurons (IPns) can be considered a neuronal phase-modulating device supporting OO Mns firing with an emergent timing mechanism and an explicit correlation code during learned eyelid movements. Optimized experimental and computational tools allowed us to determine the different causal relationships (temporal order and correlation code) during and between trials. These intra- and inter-trial timing strategies expanding from sub-second range (millisecond timing) to longer-lasting ranges (interval timing) expanded the functional domain of cerebellar timing beyond motor control. Interestingly, the results supported the above-mentioned hypothesis. The causal inferences were influenced by the precise motor and pre-motor spike timing in the cause-effect interval, and, in addition, the timing of the learned responses depended on cerebellar–Mn network causality. Furthermore, the timing of CRs depended upon the probability of simulated causal conditions in the cause-effect interval and not the mere duration of the inter-stimulus interval. In this work, the close relation between timing and causality was verified. It could thus be concluded that the firing activities of IPns may be related more to the proper performance of ongoing CRs (i.e., the proper timing as a consequence of the pertinent causality) than to their generation and/or initiation

Effects of transcranial Direct Current Stimulation (tDCS) on cortical activity: A computational modeling study.

International audienceAlthough it is well-admitted that transcranial Direct Current Stimulation (tDCS) allows for interacting with brain endogenous rhythms, the exact mechanisms by which externally-applied fields modulate the activity of neurons remain elusive. In this study a novel computational model (a neural mass model including subpopulations of pyramidal cells and inhibitory interneurons mediating synaptic currents with either slow or fast kinetics) of the cerebral cortex was elaborated to investigate the local effects of tDCS on neuronal populations based on an in-vivo experimental study. Model parameters were adjusted to reproduce evoked potentials (EPs) recorded from the somatosensory cortex of the rabbit in response to air-puffs applied on the whiskers. EPs were simulated under control condition (no tDCS) as well as under anodal and cathodal tDCS fields. Results first revealed that a feed-forward inhibition mechanism must be included in the model for accurate simulation of actual EPs (peaks and latencies). Interestingly, results revealed that externally-applied fields are also likely to affect interneurons. Indeed, when interneurons get polarized then the characteristics of simulated EPs become closer to those of real EPs. In particular, under anodal tDCS condition, more realistic EPs could be obtained when pyramidal cells were depolarized and, simultaneously, slow (resp. fast) interneurons became de- (resp. hyper-) polarized. Geometrical characteristics of interneurons might provide some explanations for this effect