Neurophysiological brain processes during perceptual decision-making have mainly been investigated under the simplified conditions of two-alternative forced-choice (2AFC) tasks. How do established principles of decision-making, obtained from these simple binary tasks, extend to more complex aspects like multiple choice-alternatives and changes of mind? Here, we first address this question theoretically: based on recent experimental findings, we extend a biophysically realistic attractor model of decision-making to account for multiple choice-alternatives and choice reevaluation. Moreover, we complement our computational approach by a psychophysical experiment, exploring how changes of mind depend on the number of choice-alternatives. Our results affirm the general conformance of attractor networks with higher-level neural processes. In particular, we found evidence for the physiological relevance of a so far unregarded bifurcation. Furthermore, our findings suggest an advantage of a pooled multi-neuron representation of choice-alternatives, and a negative correlation between reaction time and changes of mind, possibly regulated by the decision threshold. Finally, we gained testable predictions on neural firing rates during changes of mind and propose future experiments to distinguish nonlinear attractor from linear diffusion models. / Los procesos neurofisiológicos que tienen lugar en el cerebro durante la toma de decisiones basadas en fenómenos de percepción han sido investigados, principalmente, en condiciones simplificadas, en particular, de tareas con dos alternativas y elección forzada (2AFC). ¿Cómo podemos extender los principios establecidos sobre la toma de decisiones obtenidas a partir de estas tareas simples y binarias, a aspectos más complejos como decisiones con alternativas múltiples y los cambios de opinión? En esta tesis, en primer lugar, abordamos esta cuestión de manera teórica: a partir de resultados experimentales recientes, extendemos un modelo de toma de decisiones, que es un modelo con atractores realista desde el punto de vista biofísico, con el objetivo de explicar la elección con alternativas múltiples y la reevaluación de la elección. Además, complementamos nuestro enfoque computacional con un experimento psicofísico, explorando cómo los cambios de opinión dependen del número de alternativas. Nuestros resultados refuerzan la tesis de que existe una correspondencia general entre las redes de atractores y los procesos neuronales superiores. En particular, revelan la importancia fisiológica de una bifurcación que hasta ahora ha pasado inadvertida. Además, sugieren la ventaja de representar las alternativas de elección con múltiples neuronas, y la existencia de una correlación negativa entre el tiempo de reacción y los cambios de opinión, posiblemente regulada por el umbral de decisión. Finalmente, proporcionamos predicciones comprobables sobre las tasas de disparo neuronal durante los cambios de la opinión y proponemos experimentos futuros para distinguir los modelos no lineales con atractores de los modelos de difusión lineal.

Peripheral neuropaties are one of the major complications of the Peripheral Nervous System. Depsite the big importance of those pathologies, less drugs are effective for their treatment, and most of the prescribed drugs are based on the inhibition of pain. Nucleo CMP forte is a drug mainly composed of nucleotides (UMP, UDP, UTP and CMP), prescribed to patients with Peripheral Nervous System disorders. But their exact mechanism of action is still unknown. Because extracellular nucleotides can act as signalling molècules, our research group focus the studies in which are the effects of the Nucleo CMP forte drug and the triphosphate nucleotides in Schwann cells, one of the most important population in the regeneration of the Peripheral Nervous System. In response to peripheral nerve injury, Schwann cells adopt a migratiory phenotype and modify the extracellular matrix to make it permissive for cell migration and axonal regrowth. UTP and other nucleotides are released during nerve injury and activate purinergic receptors expresed on the Schwann cell surface, but little is known on the involvement of purine signalling in wound healing. Our results demonstrated that UTP treatment induces Schwann cell migration and wound healing, through the activation of the P2Y2 receptor. P2Y activation induces a biphasic MAPK activation (Early and Late) and also the activation of an extracellular metalloproteinase (MMP-2). Knockdown of the P2Y2 receptor or of MMP-2, using specific shRNAs, highly reduced cell migration and wound closure induced by UTP. MMP-2 activation evoked by injury or UTP was also mediated by the phosphorylation of all three major mitogen-activated protein kinases (MAPKs: ERK ½, p38 and JNK). Inhibition of these MAPKs decreased both MMP-2 activation and cell migration. Interestingly inhibition of MMP-2 activity, selectively blocked the late, but not the early MAPKs activation. These results suggest that MMP-2 activation and the late MAPKs phosphorylation are part of a positive feedback mechanism to maintain the migratory phenotype for wound healing. Moreover, treatment with UTP stimulates Schwann cell migration and wound repair through a MMP-2-dependent mechanism via P2Y receptors and MAPKs pathway activation.

Actualment, no hi ha consens científic respecte a la informació representada en la activitat de les célules del hipocamp. D'una banda, experiments amb humans sostenen una visión de la funció de l'hipocamp com a un sistema per l'emmagatzematge de memóries episódiques, mentre que la recerca amb rodents enfatitza una visió com a sistema cognitiu espacial. Tot i que existeix abundant evidència experimental que indica una possible sobreposició d'ambdues teories, aquesta dissociació també es manté en part en base a dades fisiològiques aparentment incompatibles. Aquesta tèsi poposa que l'hippocamp té un rol funcional que s'hauría d'analitzar en termes de la seva estructura i funció, enlloc de mitjança estudis correlació entre activitat neuronal i comportament. La identificació d'un codi a l'hipocamp, es a dir, el conjunt de principis computacionals que conformen les transformacions d'entrada i sortida de l'activitat neuronal, hauría de proporcionar un explicació unificada de la seva funció. En aquesta tèsi presentem un model teòric que descriu quantitativament i que interpreta la selectivitat de certes regions de l'hipocamp en funció de variables espaials i no-espaials, tal i com observada en experiments amb rates. Aquest resultat suggereix que multiples aspectes de la memòria expressada en humans i rodents deriven d'uns mateixos principis. Per aquest motius, proposem nous principis per la memòria, l'auto-completat de patrons i plasticitat. A més, mitjançant aplicacions robòtiques, creem d'un nexe causal entre el circuit neural i el comportament amb el que demostrem la naturalesa conjuntiva de la selectivitat neuronal observada en el hipocamp es necessària per la solució de problemes pràctics comuns, com per example la cerca d'aliments. Tot plegat, aquests resultats avancen en l'idea general de que el codi de l'hipocamp es genèric i aplicable als diversos tipus de memòries estudiades en la literatura. / There is no consensual understanding on what the activity of the hippocampus neurons represents. While experiments with humans foster a dominant view of an episodic memory system, experiments with rodents promote its role as a spatial cognitive system. Although there is abundant evidence pointing to an overlap between these two theories, the dissociation is sustained by conflicting physiological data. This thesis proposes that the functional role of the hippocampus should be analyzed in terms of its structure and function rather than by the correlation of neuronal activity and behavioral performance. The identification of the hippocampus code, i.e. the set of computational principles underlying the input-output transformations of neural activity, might ultimately provide a unifying understanding of its role. In this thesis we present a theoretical model that quantitatively describes and interprets the selectivity of regions of the hippocampus to spatial and non-spatial variables observed in experiments with rats. The results suggest that the multiple aspects of memory expressed in human and rodent data are derived form similar principles. This approach suggests new principles for memory, pattern completion and plasticity. In addition, by creating a causal tie between the neural circuitry and behavior through a robotic control framework we show that the conjunctive nature of neural selectivity observed in the hippocampus is needed for effective problem solving in real-world tasks such as foraging. Altogether, these results advance the concept that the hippocampal code is generic to the different aspects of memory highlighted in the literature.

We study two methods of data analysis which are common tools for the analysis of neuronal data. In particular, we examine how causal interactions between brain regions can be investigated using time series reflecting the neural activity in these regions. Furthermore, we analyze a method used to study the neural code that evaluates the discrimination of the responses of single neurons elicited by different stimuli. This discrimination analysis is based on the quantification of the similarity of the spike trains with time scale parametric spike train distances. In each case we describe the methods used for the analysis of the neuronal data and we characterize their specificity using simulated or exemplary experimental data. Taking into account our results, we comment the previous studies in which the methods have been applied. In particular, we focus on the interpretation of the statistical measures in terms of underlying neuronal causal connectivity and properties of the neural code, respectively. / Estudiem dos mètodes d'anàlisi de dades que són eines habituals per a l'anàlisi de dades neuronals. Concretament, examinem la manera en què les interaccions causals entre regions del cervell poden ser investigades a partir de sèries temporals que reflecteixen l'activitat neuronal d'aquestes regions. A més a més, analitzem un mètode emprat per estudiar el codi neuronal que avalua la discriminació de les respostes de neurones individuals provocades per diferents estímuls. Aquesta anàlisi de la discriminació es basa en la quantificació de la similitud de les seqüències de potencials d'acció amb distàncies amb un paràmetre d'escala temporal. Tenint en compte els nostres resultats, comentem els estudis previs en els quals aquests mètodes han estat aplicats. Concretament, ens centrem en la interpretació de les mesures estadístiques en termes de connectivitat causal neuronal subjacent i propietats del codi neuronal, respectivament.