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Serotonin (5-HT) is a key neuromodulator of medial prefrontal cortex (mPFC) functions. Pharmacological manipulation of systemic 5-HT bioavailability alters the electrical activity of mPFC neurons. However, 5-HT modulation at the population level is not well characterized. In the present study, we made single neuron extracellular recordings in the mPFC of rats performing an operant conditioning task, and analyzed the effect of systemic administration of fluoxetine (a selective serotonin reuptake inhibitor) on the information encoded in the firing activity of the neural population. Chronic (longer than 15 days), but not acute (less than 15 days), fluoxetine administration reduced the firing rate of mPFC neurons. Moreover, fluoxetine treatment enhanced pairwise entropy but diminished noise correlation and redundancy in the information encoded, thus showing how mPFC differentially encodes information as a function of 5-HT bioavailability. Information about the occurrence of the reward-predictive stimulus was maximized during reward consumption, around 3 to 4 s after the presentation of the cue, and it was higher under chronic fluoxetine treatment. However, the encoded information was less robust to noise corruption when compared to control conditions.

Serotonin (5-HT) neurotransmission has been associated with reward-related behaviour. Moreover, the serotonergic system modulates the basolateral amygdala (BLA), a structure involved in reward encoding, and reward prediction error. However, the role played by 5-HT on BLA during a reward-driven task has not been fully elucidated. In this paper, we investigated whether serotonergic modulation of the BLA is involved in reward-driven learning. To this end, we trained Long Evans rats in an operant conditioning task, and examined the effects of fluoxetine treatment (a selective serotonin reuptake inhibitor, 10 mg/kg) in combination with BLA lesions with NMDA (20 mg/mL) on extinction learning. We also investigated whether intra-BLA injection of the serotonergic 5-HT

The interdisciplinary field of neuroscience has made significant progress in recent decades, providing the scientific community in general with a new level of understanding on how the brain works beyond the store-and-fire model found in traditional neural networks. Meanwhile, Machine Learning (ML) based on established models has seen a surge of interest in the High Performance Computing (HPC) community, especially through the use of high-end accelerators, such as Graphical Processing Units(GPUs), including HPC clusters of same. In our work, we are motivated to exploit these high-performance computing developments and understand the scaling challenges for new–biologically inspired–learning models on leadership-class HPC resources. These emerging models feature sparse and random connectivity profiles that map to more loosely-coupled parallel architectures with a large number of CPU cores per node. Contrasted with traditional ML codes, these methods exploit loosely-coupled sparse data structures as opposed to tightly-coupled dense matrix computations, which benefit from SIMD-style parallelism found on GPUs. In this paper we introduce a hybrid Message Passing Interface (MPI) and Open Multi-Processing (OpenMP) parallelization scheme to accelerate and scale our computational model based on the dynamics of cortical tissue. We ran computational tests on a leadership class visualization and analysis cluster at Argonne National Laboratory. We include a study of strong and weak scaling, where we obtained parallel efficiency measures with a minimum above 87% and a maximum above 97% for simulations of our biologically inspired neural network on up to 64 computing nodes running 8 threads each. This study shows promise of the MPI+OpenMP hybrid approach to support flexible and biologically-inspired computational experimental scenarios. In addition, we present the viability in the application of these strategies in high-end leadership computers in the future. Fil: Dematties, Dario Jesus. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina Fil: Thiruvathukal, George K.. University of Chicago; Estados Unidos Fil: Rizzi, Silvio. Argonne National Laboratory; Estados Unidos Fil: Wainselboim, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina Fil: Zanutto, Bonifacio Silvano. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina

Se ha propuesto que la capacidad de adquirir lenguaje yrelaciones de equivalencia están vinculadas. Estudiosprevios muestran que estímulos relacionados porequivalencia transfieren propiedades combinatorias en unagramática artificial. Recíprocamente, en el presente trabajoanalizamos si estímulos que comparten las mismaspropiedades combinatorias por entrenamiento en unagramática artificial verifican posteriormente las propiedadesde una clase de equivalencia. Los resultados muestran quelos estímulos de una misma clase combinatoria conformanuna clase funcional que verifica las propiedades de laequivalencia (i.e. reflexividad, simetría y transitividad). Elprocesamiento de estas relaciones genera un potencialN400 que refleja un costo de procesamiento vinculado alnúmero de estímulos nodales intervinientes. Este resultadopodría explicarse en términos de un sistema proactivo queextrae y almacena regularidades estadísticas de losestímulos; conecta estímulos nuevos con lasrepresentaciones relevantes previamente adquiridas yutiliza estas asociaciones para generar predicciones sobrelos eventos futuros. It has been proposed that there is a relation between the capacity to acquire language and equivalence relations. Previous studies show that members of an equivalence class transfer combinatorial properties within an artificial grammar. Reciprocally, in the present work we analyzed whether, after training in an artificial grammar, stimuli with the same combinatorial properties verify properties of an equivalence class. Results show that stimuli of a same combinatorial class form a functional class that verifies the properties of equivalence (i.e. reflexivity; symmetry and transitivity). Processing these relations generates an N400 potential that is related to the number of nodal stimuli between stimuli pairs. This result could be explained in terms of a proactive system that extracts and retains statistical regularities of stimuli; connects new stimuli with relevant representations previously acquired and employs these associations to generate predictions of future events. Fil: Tabullo, Angel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina Fil: Iorio, Alberto Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Psicología; Argentina Fil: Zanutto, Bonifacio Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Wainselboim, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina

Sugar consumption has increased dramatically in our society, a phenomenon that is primarily associated with obesity and diabetes appearance. However, whether this overconsumption of sugar has an impact on the developing CNS remains unknown. This study investigated the long-term effects of unlimited access to sucrose using the two-bottle choice paradigm and the juvenile and adult effects were compared. Male Sprague Dawley rats had free access to water containing 10% sucrose and water during youth (PD 25?50) or adulthood (PD 75?100). Rats in the sucrose group, privileged to take sugary solution over the water. No weight differences were observed between the sucrose groups and their age-matched water controls. After treatment all animals drank only water for another 25 days. Frustration, measured as the amount of water drank after the sucrose period, was higher in young-exposed animals compared to adults. In addition, rats that consumed sucrose during youth travelled less the central zones of an open field. Sucrose consumption during youth also affected fear behavior as animals exhibited impaired extinction of fear memory compared to control, indicating that prefrontal and hippocampal function is impaired. In contrast, rats exposed to sucrose during adulthood did not behave significantly different from control on either task. The calretinin and parvalbumin GABAergic interneurons go through extensive remodeling during youth in the medial prefrontal cortex and the ventral hippocampus. Here, we found that rats exposed to sucrose during youth presented an increased expression of calretinin-immunoreactivity in the medial prefrontal cortex, but not in the ventral hippocampus, indicating that early sucrose consumption produces enduring effects on the GABA system. Altogether these results indicate that sugar overconsumption at early stages of life induces long-term effects on behaviors related to fear and anxiety in adulthood. Fil: Kruse, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Vadillo, Martín Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Miguelez Fernández, Anabel María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Rey, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Zanutto, Bonifacio Silvano. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina

Serotonin (5-HT) neurotransmission has been associated with reward-related behaviour. Moreover, the serotonergic system modulates the basolateral amygdala (BLA), a structure involved in reward encoding, and reward prediction error. However, the role played by 5-HT on BLA during a reward-driven task has not been fully elucidated. In this paper, we investigated whether serotonergic modulation of the BLA is involved in reward-driven learning. To this end, we trained Long Evans rats in an operant conditioning task, and examined the effects of fluoxetine treatment (a selective serotonin reuptake inhibitor, 10 mg/kg) in combination with BLA lesions with NMDA (20 mg/mL) on extinction learning. We also investigated whether intra-BLA injection of the serotonergic 5-HT1A receptor agonist 8-OH DPAT, or antagonist WAY-100635, alters extinction performance. We found that fluoxetine treatment strongly accelerated extinction learning, while BLA lesions partially reverted this effect and slightly impaired consolidation of extinction. Stimulation and inhibition of 5-HT1A receptors in BLA induced opposite effects to those of fluoxetine, impairing or accelerating extinction performance, respectively. Our findings suggest that 5-HT modulates reward-driven learning, and 5-HT1A receptors located in the BLA are relevant for extinction.

Many computational theories have been developed to improve artificial phonetic classificationperformance from linguistic auditory streams. However, less attention has been given topsycholinguistic data and neurophysiological features recently found in cortical tissue. Wefocus on a context in which basic linguistic units?such as phonemes?are extracted androbustly classified by humans and other animals from complex acoustic streams in speechdata. We are especially motivated by the fact that 8-month-old human infants can accomplishsegmentation of words from fluent audio streams based exclusively on the statisticalrelationships between neighboring speech sounds without any kind of supervision. In thispaper, we introduce a biologically inspired and fully unsupervised neurocomputationalapproach that incorporates key neurophysiological and anatomical cortical properties,including columnar organization, spontaneous micro-columnar formation, adaptation to contextualactivations and Sparse Distributed Representations (SDRs) produced by means ofpartial N-Methyl-D-aspartic acid (NMDA) depolarization. Its feature abstraction capabilitiesshow promising phonetic invariance and generalization attributes. Our model improves theperformance of a Support Vector Machine (SVM) classifier for monosyllabic, disyllabic andtrisyllabic word classification tasks in the presence of environmental disturbances such aswhite noise, reverberation, and pitch and voice variations. Furthermore, our approachemphasizes potential self-organizing cortical principles achieving improvement without anykind of optimization guidance which could minimize hypothetical loss functions by meansof?for example?backpropagation. Thus, our computational model outperforms multiresolutionspectro-temporal auditory feature representations using only the statistical sequentialstructure immerse in the phonotactic rules of the input stream. Fil: Dematties, Dario Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina Fil: Rizzi, Silvio. Argonne National Laboratory; Estados Unidos Fil: Thiruvathukal, George. Loyola University; Estados Unidos Fil: Wainselboim, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina Fil: Zanutto, Bonifacio Silvano. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina

Schizophrenia and bipolar disorder are psychiatric syndromes with a significant social and economic burden that share a common symptom, psychosis, attributed to excessive dopamine release. Despite years of intensive research, the causes of these devastating diseases are still unknown. In this work, a mouse line with a selective deletion of the molecular target of antipsychotics, dopamine D2 receptors, from the most affected neuron subtype in patients, parvalbumin interneurons, results in animals with schizophrenia-like phenotypes and resistance to the broadly used antipsychotic aripiprazole. Therefore, this genetic dissection provides clues about the intrinsic molecular mechanism leading to a dysregulated dopamine system and the development of psychiatric conditions like schizophrenia, bringing opportunities to develop diagnostic and treatment approaches.

Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis. Here, we show that selective dopamine D2 receptor deletion from parvalbumin interneurons in mouse causes an impaired inhibitory activity in the ventral hippocampus and a dysregulated dopaminergic system. Conditional mutant animals show adult onset of schizophrenia-like behaviors and molecular, cellular, and physiological endophenotypes as previously described from postmortem brain studies of patients with schizophrenia. Our findings show that dopamine D2 receptor expression on parvalbumin interneurons is required to modulate and limit pyramidal neuron activity, which may prevent the dysregulation of the dopaminergic system. Fil: Tomasella, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Bechelli, Maria Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Ogando, Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Mininni, Camilo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Di Guilmi, Mariano Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: de Fino, Fernanda Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Zanutto, Bonifacio Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Marin Burgin, Antonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina

Dopamine encodes reward and its prediction in reinforcement learning. Catechol-O-methyltransferase (COMT) activity in the medial prefrontal cortex (mPFC) has been shown to influence cognitive abilities by modifying dopamine clearance. Nevertheless, it is unknown how COMT in the mPFC influences operant learning. Systemic entacapone (50mg/kg), as well as local entacapone (3pg) and recombinant COMT (17μg) in the mPFC were administered to male Long Evans rats prior to training in an operant conditioning task. We found that systemic and local administration of the COMT inhibitor entacapone significantly improves learning performance. Conversely, recombinant COMT administration totally impaired learning. These data have been interpreted through a computational model where the phasic firing of dopaminergic neurons was computed by means of a temporal difference algorithm and dopamine bioavailability in the mPFC was simulated with a gating window. The duration of this window was selected to simulate the effects of inhibited or enhanced COMT activity (by entacapone or recombinant COMT respectively). The model accounts for an improved performance reproducing the entacapone effects, and a detrimental impact on learning when the clearance is increased reproducing the recombinant COMT effects. The experimental and computational results show that learning performance can be deeply influenced by COMT manipulations in the mPFC. Fil: Rapanelli, Maximiliano. University Of Yale; Estados Unidos Fil: Frick, Luciana Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Miguelez Fernández, Anabel María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Zanutto, Bonifacio Silvano. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina

The prefrontal cortex (PFC) is a key brain structure for decision making, behavioural flexibility and working memory. Neurons in PFC encode relevant stimuli through changes in their firing rate, although the metabolic cost of spiking activity puts strong constrains to neural codes based on firing rate modulation. Thus, how PFC neural populations code relevant information in an efficient way is not clearly understood. To address this issue we made single unit recordings in the PFC of rats performing a GO/NOGO discrimination task and ana-lysed how entropy between pairs of neurons changes during cue presentation. We found that entropy rises only during reward-predicting cues. Moreover, this change in entropy occurred along an increase in the efficiency of the whole process. We studied possible mechanisms behind the efficient gain in entropy by means of a two neuron leaky integrate- and-fire model, and found that a precise relationship between synaptic efficacy and firing rate is required to explain the experimentally observed results. Fil: Mininni, Camilo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Caiafa, César Federico. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; Argentina Fil: Zanutto, Bonifacio Silvano. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Tseng, Kuei Y.. University of Illinois; Estados Unidos Fil: Lew, Sergio Eduardo. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina

Background While spherical treadmills are widely used in mouse models, there are only a few experimental setups suitable for adult rats, and none of them include head-fixation. New method We introduce a novel spherical treadmill apparatus for head-fixed rats that allows a wide repertory of natural responses. The rat is secured to a frame and placed on a freely rotating sphere. While being head-fixed, it can walk in any direction and perform different motor tasks. Comparison with existing methods Instead of being air-lifted, which is acceptable for light animals, the treadmill is sustained by three spherical bearings ensuring a smooth rotation in any direction. Movement detection is accomplished using a video camera that registers a dot pattern plotted on the sphere. Results Long Evans rats were trained to perform an auditory discrimination task in a Go/No-Go (walking/not-walking) paradigm. Animals were able to successfully discriminate between a 1 kHz and a 8 kHz auditory stimulus and execute the correct response, reaching the learning criterion (80% of correct responses) in approximately 20 training sessions. Conclusions Our system broadens the possibilities of head-fixation experiments in adult rats making them compatible with spatial navigation on a spherical treadmill. Fil: Miguelez Fernández, Anabel María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Burman, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina Fil: Martínez Cáceres, Alfredo I.. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina Fil: Mininni, Camilo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Zanutto, Bonifacio Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina Fil: Lew, Sergio Eduardo. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina

Most languages have a basic or “canonical” word order, which determines the relative positions of the subject (S), the verb (V), and the object (O) in a typical declarative sentence. The frequency of occurrence of the six possible word orders among world languages is not distributed uniformly. While SVO and SOV represent around 85% of world languages, orders like VSO (9%) or OSV (0.5%) are much less frequent or extremely rare. One possible explanation for this asymmetry is that biological and cognitive constraints for structured sequence processing make some word orders easier to be processed than others. Therefore, the high frequency of these word orders would be related to their higher learnability. The aim of the present study was to compare the learnability of different word orders between groups of adult subjects. Four artificial languages with different word orders were trained: two frequent (SVO, SOV) and two infrequent (VSO, OSV). In a test stage, subjects were asked to discriminate between new correct sentences and syntax or semantic violations. Higher performance rates and faster responses were observed for more frequent word orders. The results support the hypothesis that more frequent word orders are more easily learned.

A wide range of studies have found late positive ERP components in response to anomalies during processing of structured sequences. In language studies, this component is named Syntactic Positive Shift (SPS) or P600. It is characterized by an increase in potential peaking around 600 ms after the appearance of the syntactic anomaly and has a centroparietal topography. Similar late positive components were found more recently in non-linguistic contexts. These results have led to the hypothesis that these components index the detection of anomalies in rule-governed sequences, or the access to abstract rule representations, regardless of the nature of the stimuli. Additionally, there is evidence showing that the SPS/P600 is sensitive to probability manipulations, which affect the subjects’ expectancy of the stimuli. Our aim in the present work was to address the hypothesis that the late positive component is modulated by the subject's expectancy of the stimuli. To do so, we employed an artificial grammar learning task, and controlled the frequency of presentation to different kind of sequences during training. Results showed that certain sequence types elicited a late positive component which was modulated by different factors in two distinct time windows. In an earlier window, the component was higher for sequences which had a low or null probability of occurrence during training, while in a later window, the component was higher for incorrect than correct sequences. Furthermore, this late window effect was absent in those subjects whose performance was not significantly above chance. Two possible explanations for this effect are suggested.

We conducted an ERP study of derived relations within stimulus equivalence classes. After successful training of baseline relations, subjects performed a priming task and their ERP responses to the following prime-target pairs were registered: (a) stimuli related through symmetry, (b) stimuli nonrelated through symmetry, (c) stimuli related through symmetry-transivity combined (equivalence), and (d) stimuli nonrelated through equivalence. A P300-like component was observed in related targets, which was earlier for symmetry and later for symmetry-transitivity, whereas an N400-like effect was found in nonequivalent stimuli. The P300 delay after equivalent stimuli was interpreted as evidence that relational strength within equivalence classes is inversely related to the number of logical operations required to link the stimuli. The N400 effect for nonequivalent stimuli was congruent with previous literature, and suggests a potential overlap between the neural correlates of priming in language and stimulus equivalence. Fil: Tabullo, Angel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina Fil: Yorio, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Zanutto, Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Wainselboim, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina

Semantic priming has been widely observed at both behavioral and electrophysiological levels as reductions in response times and N400 magnitudes respectively. However, the possibility that stimulus relations derived from associative learning elicit N400 priming effects comparable to those found in language has not been properly addressed yet. Equivalence relations emerge after establishing a set of arbitrary and intra-experimentally defined relations through associative learning, thus allowing the study of derived stimulus relations in the absence of semantic content. The present study aimed to compare ERP correlates of priming in semantically related words and pseudowords related through equivalence. We found similar behavioral and N400 effects when comparing unrelated vs related prime-target pairs in language and stimulus equivalence tasks, suggesting that priming engages at least partially overlapping neural mechanisms in both contexts. In addition, we found a posteriorly distributed late positivity in the semantic priming task only, which may be reflecting language-specific processing. Fil: Tabullo, Angel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Yorio, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Zanutto, Bonifacio Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Wainselboim, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina

Serotonin (5-HT) has been proposed as a possible encoder of reward. Nevertheless, the role of this neurotransmitter in reward-based tasks is not well understood. Given that the major serotonergic circuit in the rat brain comprises the dorsal raphe nuclei and the medial prefrontal cortex (mPFC), and because the latter structure is involved in the control of complex behaviors and expresses 1A (5-HT1A), 2A (5-HT2A), and 3 (5-HT3) receptors, the aim was to study the role of 5-HT and of these receptors in the acquisition and extinction of a reward-dependent operant conditioning task. Long Evans rats were trained in an operant conditioning task while receiving fluoxetine (serotonin reuptake inhibitor, 10 mg/kg), tianeptine (serotonin reuptake enhancer, 10 mg/kg), buspirone (5-HT1A partial agonist, 10 mg/kg), risperidone (5-HT2A antagonist, 1 mg/kg), ondansetron (5-HT3 antagonist, 2 mg/kg) or vehicle. Then, animals that acquired the operant conditioning without any treatment were trained to extinct the task in the presence of the pharmacological agents. Fluoxetine impaired acquisition but improved extinction. Tianeptine administration induced the opposite effects. Buspirone induced a mild deficit in acquisition and had no effects during the extinction phase. Risperidone administration resulted in learning deficits during the acquisition phase, although it promoted improved extinction. Ondansetron treatment showed a deleterious effect in the acquisition phase and an overall improvement in the extinction phase. These data showed a differential role of 5-HT in the acquisition and extinction of an operant conditioning task, suggesting that it may have a dual function in reward encoding. Fil: Frick, Luciana Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Bernardez Vidal, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Hocht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Zanutto, Bonifacio Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Rapanelli, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina

One of the most valuable mechanisms in animal self-adaptation is the ability to switch between exploration and exploitation strategies. In this work, we present a computational model that learns visual discrimination paradigms and adapts its behavior whereupon rules change. In the model, dopamine and norepinephrine neurons are proposed as detectors of changes in the environment. Dopamine modulates the excitability and plasticity of artificial neurons in the prefrontal cortex and motor-related structures. These neurons change their synaptic weights following a Hebbian or anti-Hebbian rule depending on the amount of released dopamine and, as the reward rate increases, it induces exploitative behaviors. On the other hand, tonic levels of norepinephrine modulate both, information flows towards motor structures and the excitability of dopaminergic neurons, facilitating the switch from exploitation to exploration strategies. The computational model predicts behavioral and physiological results and provides a computational framework to the exploration-exploitation dilemma in self-adaptive agents.

Blockade of N-methyl-d-aspartate receptor (NMDA) by the noncompetitive NMDA receptor (NMDAR) antagonist MK-801 produces behavioral abnormalities and alterations in prefrontal cortex (PFC) functioning. Due to the critical role of the PFC in operant conditioning task learning, we evaluated the effects of acute, repeated postnatal injections of MK-801 (0.1 mg/kg) on learning performance. We injected Long-Evans rats i.p. with MK-801 (0.1 mg/kg) using three different administration schedules: injection 40 min before beginning the task (during) (n = 12); injection twice daily for six consecutive days prior to beginning the experimental procedures (prior) (n = 12); or twice daily subcutaneous injections from postnatal day 7 to 11 (postnatal) (n = 12). Next, we orally administered risperidone (serotonin receptor 2A and dopamine receptor 2 antagonist, 1 mg/kg) or buspirone (serotonin receptor 1A partial agonist, 10 mg/kg) to animals treated with the MK-801 schedule described above. The postnatal and prior administration schedules produced severe learning deficits, whereas injection of MK-801 just before training sessions had only mild effects on acquisition of an operant conditioning. Risperidone was able to reverse the detrimental effect of MK-801 in the animals that were treated with MK-801 during and prior training sessions. In contrast, buspirone was only effective at mitigating the cognitive deficits induced by MK-801 when administered during the training procedures. The data demonstrates that NMDA antagonism disrupts basic mechanisms of learning in a simple PFC-mediated operant conditioning task, and that buspirone and risperidone failed to attenuate the learning deficits when NMDA neurotransmission was blocked in the early stages of the postnatal period. Fil: Rapanelli, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Fil: Frick, Luciana Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Fil: Bernardez Vidal, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Fil: Zanutto, Bonifacio Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina

Artificial grammars have been widely applied to the study of sequential learning in language, but few studies have directly compared the neural correlates of artificial and native grammar processing. In this study, we examined Event Related Potentials (ERPs) elicited by structural anomalies in semantic-free artificial grammar sequences and sentences from the subjects? native language (Spanish). Although ERPs differed during early stages, we observed similar posterior negativities (N400) and P600 effects in a late stage. We interpret these results as evidence of at least partially shared neural mechanisms for processing of language and artificial grammars. We suggest that in both the natural and artificial grammars, the N400 and P600 components we observed can be explained as the result of unfulfilled predictions about incoming stimuli. Fil: Tabullo, Angel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Sevilla, Yamila Alejandra. Universidad de Buenos Aires. Facultad de Filosofia y Letras. Instituto de Linguística; Argentina Fil: Segura, Enrique Teodoro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Zanutto, Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina Fil: Wainselboim, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina

Equivalence relations (ERs) are logical entities that emerge concurrently with the development of language capabilities. In this work we propose a computational model that learns to build ERs by learning simple conditional rules. The model includes visual areas, dopaminergic, and noradrenergic structures as well as prefrontal and motor areas, each of them modeled as a group of continuous valued units that simulate clusters of real neurons. In the model, lateral interaction between neurons of visual structures and top-down modulation of prefrontal/premotor structures over the activity of neurons in visual structures are necessary conditions for learning the paradigm. In terms of the number of neurons and their interaction, we show that a minimal structural complexity is required for learning ERs among conditioned stimuli. Paradoxically, the emergence of the ER drives a reduction in the number of neurons needed to maintain those previously specific stimulus–response learned rules, allowing an efficient use of neuronal resources. Fil: Lew, Sergio E.. Universidad de Buenos Aires. Facultad de Ingenieria. Instituto de Ingeniería Biomédica; Argentina Fil: Zanutto, Bonifacio Silvano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ingenieria. Instituto de Ingeniería Biomédica; Argentina

rules can be learned by several species (not only humans). We propose a biologically plausible model for same/different discrimination, that can point towards the neural basis of abstract concept learning. By including a neural adaptation mechanism to a discriminator model formerly introduced in the literature, selective clusters of neurons fire depending on whether or not the stimuli compared are the same or not. These selective neurons are consistent with experimental findings in the literature. Moreover, reward and attention can modulate the relative strength of each attribute/feature of the stimulus, so more complex abstract discriminations can be achieved using the proposed model as a building block. As a formal model, it can be easily incorporated into several applications in robotics and intelligent machines.

The Basal Ganglia (BG) are a group of nuclei, in the brain of mammalians and other vertebrates, strongly connected with the cerebral cortex, thalamus and other brain areas. The BG are associated with several brain functions including learning and motor control. When there is cortical activation, there is a strong synchronization between BG and cortex, i.e. when a given task is being executed or in the case of Parkinson disease[1], [2]. If we consider the internal segment of the Globus Pallidus (GPi) there is synchronism between GPi-cortex at frequencies as low as 3Hz to as high as 85Hz [1], [3]. In the other hand, in a delta sleep or in an anesthetized case, a very low frequency correlation is observed (1-10 Hz), but no high frequency correlation between GPi-cortex [1], [2], [3]. It is unknown why this decorrelation happens. But It is agreement that when there is no pattern to select, like in delta sleep or with an anesthetized model, the BG network would maintain the GPi and cortex decorrelated at high frequencies. Many thalamus-BG and thalamus-BG-cortex loops are modulators of the BG activity. Particularly there exists an anatomic thalamus-BG loop, formed by GPi, intralaminar thalamic nuclei (IL) and Subthalamic Nucleus (STN) [4]. Using a computational model, based on an "Integrate and Fire" neural network, we analyzed the IL nucleus as a modulator of the so-called hyper direct pathway. Our results show that, in an anesthetic case, this thalamic path could be relevant to allow a high frequency decorrelated state between the GPi and cortex.

In adult animals, the nervous system controls the long-term mean blood pressure. The nucleus of the tractus solitarius (NTS) behaves as a comparator between its rostral afferents (the reference) and the cardioreceptor afferents (the feedback). It is hypothesized that, during ontogeny, the nervous system learns the sympathetic efferents from the chemoreceptor feedback. This process is simulated by a neural network model. In a stable metabolism, the model converges to a state in which all the tissues are irrigated with optimal oxygen and carbon dioxide levels.

Background Physiological experiments have shown that the mean arterial blood pressure (MAP) can not be regulated after chemo and cardiopulmonary receptor denervation. Neuro-physiological information suggests that the nucleus tractus solitarius (NTS) is the only structure that receives information from its rostral neural nuclei and from the cardiovascular receptors and projects to nuclei that regulate the circulatory variables. Methods From a control theory perspective, to answer if the cardiovascular regulation has a set point, we should find out whether in the cardiovascular control there is something equivalent to a comparator evaluating the error signal (between the rostral projections to the NTS and the feedback inputs). The NTS would function as a comparator if: a) its lesion suppresses cardiovascular regulation; b) the negative feedback loop still responds normally to perturbations (such as mechanical or electrical) after cutting the rostral afferent fibers to the NTS; c) perturbation of rostral neural structures (RNS) to the NTS modifies the set point without changing the dynamics of the elicited response; and d) cardiovascular responses to perturbations on neural structures within the negative feedback loop compensate for much faster than perturbations on the NTS rostral structures. Results From the control theory framework, experimental evidence found currently in the literature plus experimental results from our group was put together showing that the above-mentioned conditions (to show that the NTS functions as a comparator) are satisfied. Conclusions Physiological experiments suggest that long-term blood pressure is regulated by the nervous system. The NTS functions as a comparator (evaluating the error signal) between its RNS and the cardiovascular receptor afferents and projects to nuclei that regulate the circulatory variables. The mean arterial pressure (MAP) is regulated by the feedback of chemo and cardiopulmonary receptors and the baroreflex would stabilize the short term pressure value to the prevailing carotid MAP. The discharge rates of rostral neural projections to the NTS would function as the set point of the closed and open loops of cardiovascular control. No doubt, then, the RNS play a functional role not only under steady-state conditions, but also in different behaviors and pathologies.