Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic

Barcelona, Spain

Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic

Barcelona, Spain

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Moral-Vico J.,CSIC - Institute of Materials Science | Carretero N.M.,CSIC - Institute of Materials Science | Perez E.,CSIC - Institute of Materials Science | Sunol C.,Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic | And 6 more authors.
Electrochimica Acta | Year: 2013

Polypyrrole (PPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymers are being applied in a number of devices due to their intercalation redox activity and conductivity. Their use as electrode materials in bio-applications has been hindered by the large irreproducibility of surfaces for the most common counterions, specially in the PEDOT case. This work shows that the best behavior in neural cell cultures does not belong to one or the other polymer, but to a combination of both, and specific counter-ions. Polypyrrole, with surface potentials closer to biological systems, becomes an optimal surface, but only when electrodeposited on PEDOT and with some biologically active amino acids acting as counter-ions. Characterizations of the surface PPy and its electrochemical response are performed. The formation of bilayers, with PPy deposited on PEDOT, significantly changes the conductivity and charge capacity of PPy polymer, largely improving the neural cell growth on these polymers in a reproducible manner. © 2013 Elsevier Ltd.


Carretero N.M.,CSIC - Institute of Materials Science | Lichtenstein M.P.,Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic | Perez E.,CSIC - Institute of Materials Science | Cabana L.,CSIC - Institute of Materials Science | And 3 more authors.
Acta Biomaterialia | Year: 2014

Nanostructured iridium oxide-carbon nanotube hybrids (IrOx-CNT) deposited as thin films by dynamic electrochemical methods are suggested as novel materials for neural electrodes. Single-walled carbon nanotubes (SWCNT) serve as scaffolds for growing the oxide, yielding a tridimensional structure with improved physical, chemical and electrical properties, in addition to high biocompatibility. In biological environments, SWCNT encapsulation by IrOx makes more resistant electrodes and prevents the nanotube release to the media, preventing cellular toxicity. Chemical, electrochemical, structural and surface characterization of the hybrids has been accomplished. The high performance of the material in electrochemical measurements and the significant increase in cathodal charge storage capacity obtained for the hybrid in comparison with bare IrOx represent a significant advance in electric field application in biosystems, while its cyclability is also an order of magnitude greater than pure IrOx. Moreover, experiments using in vitro neuronal cultures suggest high biocompatibility for IrOx-CNT coatings and full functionality of neurons, validating this material for use in neural electrodes. © 2014 Acta Materialia Inc.


Penas-Cazorla R.,Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic | Vilaro M.T.,Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic | Vilaro M.T.,CIBER ISCIII
Brain Structure and Function | Year: 2015

Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists. © 2014, Springer-Verlag Berlin Heidelberg.


Carretero N.M.,CSIC - Institute of Materials Science | Lichtenstein M.P.,Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic | Perez E.,CSIC - Institute of Materials Science | Sandoval S.,CSIC - Institute of Materials Science | And 4 more authors.
Electrochimica Acta | Year: 2015

Hybrid materials based on iridium oxide and graphene oxide, and graphite oxide as reference, are reported as biocompatible electrodes for the neural system. An electrodeposition process based on dynamic potential sweeps, allows an optimal adherence of coatings to the platinum substrate. The resulting electrochemical properties evidence an order of magnitude increase in charge capacity with respect to iridium oxide, and a quasi reversible cyclability for the electrode that expands to more than a thousand cycles for the graphene oxide case. Such stability upon cycling is also an order of magnitude larger than that of IrOx. Neuronal cell cultures show full biocompatibility even in absence of growth factors, and sustain near 100% survival rates and optimal development of neurites. Together with previously reported hybrid IrOx-carbon nanotubes, IrOx-graphene oxide hybrids open the field of materials to be used in the neural system. © 2014 Elsevier Ltd. All rights reserved.


Penas-Cazorla R.,Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic | Vilaro M.T.,Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic | Vilaro M.T.,CIBER ISCIII
Brain Structure and Function | Year: 2014

Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists. © 2014 Springer-Verlag Berlin Heidelberg.


Lopez-Gil X.,Experimental 7T MRI Unit | Amat-Roldan I.,Expert Ymaging S.L. | Tudela R.,Experimental 7T MRI Unit | Tudela R.,University of Barcelona | And 7 more authors.
Frontiers in Aging Neuroscience | Year: 2014

The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm3 isometric resolution at 10, 14, 18, 22, 26 and 40 weeks after birth. Diffusion weighted imaging was analyzed in 2 different ways, by regional characterization of diffusion tensor imaging indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, diffusion tensor imaging scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and grey matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional 3-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.


PubMed | Sloan Kettering Cancer Center, Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic, New York Medical College and Columbia University
Type: | Journal: Nature communications | Year: 2016

Parental behavioural traits can be transmitted by non-genetic mechanisms to the offspring. Although trait transmission via sperm has been extensively researched, epidemiological studies indicate the exclusive/prominent maternal transmission of many non-genetic traits. Since maternal conditions impact the offspring during gametogenesis and through fetal/early-postnatal life, the resultant phenotype is likely the aggregate of consecutive germline and somatic effects; a concept that has not been previously studied. Here, we dissected a complex maternally transmitted phenotype, reminiscent of comorbid generalized anxiety/depression, to elementary behaviours/domains and their transmission mechanisms in mice. We show that four anxiety/stress-reactive traits are transmitted via independent iterative-somatic and gametic epigenetic mechanisms across multiple generations. Somatic/gametic transmission alters DNA methylation at enhancers within synaptic genes whose functions can be linked to the behavioural traits. Traits have generation-dependent penetrance and sex specificity resulting in pleiotropy. A transmission-pathway-based concept can refine current inheritance models of psychiatric diseases and facilitate the development of better animal models and new therapeutic approaches.


Castane Anna A.,University of Cambridge | Castane Anna A.,Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic | Theobald D.E.H.,University of Cambridge | Robbins T.W.,University of Cambridge
Behavioural Brain Research | Year: 2010

Impairments in reversal learning have been attributed to orbitofrontal cortex (OFC) dysfunction in many species. However, the role of subcortical areas interconnected with the OFC such as the striatum remains poorly understood. This study directly evaluated the contribution of core and shell sub-regions of the nucleus accumbens (NAc), dorsomedial (DMS) and dorsolateral (DLS) striatum to reversal learning of an instrumental two-lever spatial discrimination task in rats. Selective NAc core, DMS and DLS lesions were achieved with microinjections of quinolinic acid and NAc shell lesions with ibotenic acid. Damage to NAc core or shell did not affect retention of a previously acquired instrumental spatial discrimination. In contrast, DLS and DMS lesions produced changes in aspects of discrimination performance such as the latency to collect earned food pellets. Neither NAc core or shell lesions nor DLS lesions affected the main indices of reversal performance. Conversely, DMS lesion rats showed a significant impairment in reversal learning. DMS damage increased the number of errors to reach criteria that were perseverative in nature. The deficit in reversal learning in DMS lesion rats was not associated with an impairment to extinguish instrumental responding. There were no effects on spontaneous locomotor activity. Our data are in agreement with recent work showing that lesions of the medial striatum in marmoset monkeys produce perseverative impairments during a serial visual discrimination reversal task and support the hypothesis that dorsomedial striatal dysfunction contributes to pathological perseveration, which is a common feature of many psychiatric disorders. © 2010 Elsevier B.V.


Cano-Colino M.,Institute dInvestigacions Biomediques August Pi I Sunyer IDIBAPS | Almeida R.,Institute dInvestigacions Biomediques August Pi I Sunyer IDIBAPS | Almeida R.,Karolinska Institutet | Gomez-Cabrero D.,Institute dInvestigacions Biomediques August Pi I Sunyer IDIBAPS | And 5 more authors.
Cerebral Cortex | Year: 2014

The prefrontal cortex (PFC) contains a dense network of serotonergic [serotonin, 5-hydroxytryptamine (5-HT)] axons, and endogenous 5-HT markedly modulates PFC neuronal function via several postsynaptic receptors. The therapeutic action of atypical antipsychotic drugs, acting mainly via 5-HT receptors, also suggests a role for serotonergic neurotransmission in cognitive functions. However, psychopharmacological studies have failed to find a consistent relationship between serotonergic transmission and cognitive functions of the PFC, including spatial working memory (SWM). Here, we built a computational network model to investigate 5-HT modulation of SWM in the PFC. We found that 5-HT modulates network's SWM performance nonmonotonically via 5-HT1A and 5-HT2A receptors, following an inverted U-shape. This relationship may contribute to blur the effects of serotonergic agents in previous SWM group-based behavioral studies. Our simulations also showed that errors occurring at low and high 5-HT concentrations are due to different network dynamics instabilities, suggesting that these 2 conditions can be distinguished experimentally based on their distinct dependency on experimental variables. We inferred specific predictions regarding the expected behavioral effects of serotonergic agents in 2 classic working-memory tasks. Our results underscore the relevance of identifying different error types in SWM tasks in order to reveal the association between neuromodulatory systems and SWM. © The Author 2013. Published by Oxford University Press. All rights reserved.


PubMed | Institute Dinvestigacions Biomediques Of Barcelona Iibb Csic
Type: Journal Article | Journal: Brain structure & function | Year: 2015

Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.

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