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

The effect of media professionalization on cognitive neurodynamics during audiovisual cuts

Experts apply their experience to the proper development of their routine activities. Their acquired expertise or professionalization is expected to help in the development of those recurring tasks. Media professionals spend their daily work watching narrative contents on screens, so learning how they manage visual perception of those contents could be of interest in an increasingly audiovisual society. Media works require not only the understanding of the storytelling, but also the decoding of the formal rules and presentations. We recorded electroencephalographic (EEG) signals from 36 participants (18 media professionals and 18 non-media professionals) while they were watching audiovisual contents, and compared their eyeblink rate and their brain activity and connectivity. We found that media professionals decreased their blink rate after the cuts, suggesting that they can better manage the loss of visual information that blinks entail by sparing them when new visual information is being presented. Cuts triggered similar activation of basic brain processing in the visual cortex of the two groups, but different processing in medial and frontal cortical areas, where media professionals showed a lower activity. Effective brain connectivity occurred in a more organized way in media professionals-possibly due to a better communication between cortical areas that are coordinated for decoding new visual content after cuts

Viewers change eye-blink rate by predicting narrative content

Eye blinks provoke a loss of visual information. However, we are not constantly making conscious decisions about the appropriate moment to blink. The presence or absence of eye blinks also denotes levels of attention. We presented three movies with the exact same narrative but different styles of editing and recorded participants' eye blinks. We found that moments of increased or decreased eye blinks by viewers coincided with the same content in the different movie styles. The moments of increased eye blinks corresponded to those when the actor leaves the scene and when the movie repeats the same action for a while. The moments of decreased eye blinks corresponded to actions where visual information was crucial to proper understanding of the scene presented. According to these results, viewers' attention is more related to narrative content than to the style of editing when watching movies

Brain symmetry in alpha band when watching cuts in movies

Altres ajuts: Junta de Andalucía (PY18-823 i BIO-122)The purpose of this study is to determine if there is asymmetry in the brain activity between both hemispheres while watching cuts in movies. We presented videos with cuts to 36 participants, registered electrical brain activity through electroencephalography (EEG) and analyzed asymmetry in frontal, somatomotor, temporal, parietal and occipital areas. EEG power and alpha (8-13 Hz) asymmetry were analyzed based on 4032 epochs (112 epochs from videos × 36 participants) in each hemisphere. On average, we found negative asymmetry, indicating a greater alpha power in the left hemisphere and a greater activity in the right hemisphere in frontal, temporal and occipital areas. The opposite was found in somatomotor and temporal areas. However, with a high inter-subjects variability, these asymmetries did not seem to be significant. Our results suggest that cuts in audiovisuals do not provoke any specific asymmetrical brain activity in the alpha band in viewers. We conclude that brain asymmetry when decoding audiovisual content may be more related with narrative content than with formal style

Dissociation between CA3-CA1 synaptic plasticity and associative learning in TgNTRK3 transgenic mice

Neurotrophins and their cognate receptors might serve as feedback regulators for the efficacy of synaptic transmission.Weanalyzed miceoverexpressing TrkC (TgNTRK3) for synaptic plasticity and the expression of glutamate receptor subunits. Animals were conditionedusing a trace [conditioned stimulus (CS), tone; unconditioned stimulus (US), shock] paradigm. A single electrical pulse presented to theSchaffer collateral– commissural pathway during the CS–US interval evoked a monosynaptic field EPSP (fEPSP) at ipsilateral CA1pyramidal cells. In wild types, fEPSP slopes increased across conditioning sessions and decreased during extinction, being linearlyrelated to learning evolution. In contrast, fEPSPs in TgNTRK3 animals reached extremely high values, not accompanied with a proportionateincrease in their learning curves. Long-term potentiation evoked in conscious TgNTRK3 was also significantly longer lasting thanin wild-type mice. These functional alterations were accompanied by significant changes inNR1andNR2BNMDAreceptor subunits, withno modification of NR1Ser 896 or NR1Ser 897 phosphorylation. No changes of AMPA and kainate subunits were detected. Results indicatethat the NT-3/TrkC cascade could regulate synaptic transmission and plasticity through modulation of glutamatergic transmission at theCA3–CA1 synapse

Eyeblink rate watching classical Hollywood and post-classical MTV editing styles, in media and non-media professionals

While movie edition creates a discontinuity in audio-visual works for narrative and economy-ofstorytelling reasons, eyeblink creates a discontinuity in visual perception for protective and cognitive reasons. We were interested in analyzing eyeblink rate linked to cinematographic edition styles. We created three video stimuli with different editing styles and analyzed spontaneous blink rate in participants (N=40). We were also interested in looking for different perceptive patterns in blink rate related to media professionalization. For that, of our participants, half (n=20) were media professionals, and the other half were not. According to our results, MTV editing style inhibits eyeblinks more than Hollywood style and one-shot style. More interestingly, we obtained differences in visual perception related to media professionalization: we found that media professionals inhibit eyeblink rate substantially compared with non-media professionals, in any style of audio-visual edition

Astrocytic BDNF and TrkB regulate severity and neuronal activity in mouse models of temporal lobe epilepsy

Astrocytes have emerged as crucial regulators of neuronal network activity, synapse formation, and underlying behavioral and cognitive processes. Despite some pathways have been identified, the communication between astrocytes and neurons remains to be completely elucidated. Unraveling this communication is crucial to design potential treatments for neurological disorders like temporal lobe epilepsy (TLE). The BDNF and TrkB molecules have emerged as very promising therapeutic targets. However, their modulation can be accompanied by several off-target effects such as excitotoxicity in case of uncontrolled upregulation or dementia, amnesia, and other memory disorders in case of downregulation. Here, we show that BDNF and TrkB from astrocytes modulate neuronal dysfunction in TLE models. First, conditional overexpression of BDNF from astrocytes worsened the phenotype in the lithium-pilocarpine mouse model. Our evidences pointed out to the astrocytic pro-BDNF isoform as a major player of this altered phenotype. Conversely, specific genetic deletion of BDNF in astrocytes prevented the increase in the number of firing neurons and the global firing rate in an in vitro model of TLE. Regarding to the TrkB, we generated mice with a genetic deletion of TrkB specifically in hippocampal neurons or astrocytes. Interestingly, both lines displayed neuroprotection in the lithium-pilocarpine model but only the mice with genetic deletion of TrkB in astrocytes showed significantly preserved spatial learning skills. These data identify the astrocytic BDNF and TrkB molecules as promising therapeutic targets for the treatment of TLE

The AMPA receptor positive allosteric modulator S 47445 rescues in vivo CA3-CA1 long-term potentiation and structural synaptic changes in old mice

Positive allosteric modulators of cc-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are small molecules that decrease deactivation of AMPARs via an allosteric site. These molecules keep the receptor in an active state. Interestingly, this type of modulator has been proposed for treating cognitive decline in ageing, dementias, and Alzheimer's disease (AD). S 47445 (8-cyclopropyl-3[2-(3-fluorophenyflethy1]-7,8-dihydro-3H-[1,3]oxazino[6,5-g][1,2,3]benzotriazine-4,9-dione) is a novel AMPAR positive allosteric modulator (AMPA-PAM). Here, the mechanisms by which S 47445 could improve synaptic strength and connectivity were studied and compared between young and old mice. A single oral administration of S 47445 at 10 mg/kg significantly increased long-term potentiation (LTP) in CA3-CA1 hippocampal synapses in alert young mice in comparison to control mice. Moreover, chronic treatment with S 47445 at 10 mg/kg in old alert animals significantly counteracted the deficit of LTP due to age. Accordingly, chronic treatment with S 47445 at 10 mg/kg seems to preserve synaptic cytoarchitecture in old mice as compared with young control mice. It was shown that the significant decreases in number and size of pre-synaptic buttons stained for VGlutl, and post-synaptic dendritic spines stained for spinophilin, observed in old mice were significantly prevented after chronic treatment with 10 mg/kg of S 47445. Altogether, by its different effects on LTP, VGlutl-positive particles, and spinophilin, S 47445 is able to modulate both the structure and function of hippocampal excitatory synapses known to be involved in learning and memory processes. These results open a new window for the treatment of specific age-dependent cognitive decline and dementias such as AD. (C) 2017 The Authors. Published by Elsevier Ltd

Regulation of GABAA and Glutamate Receptor Expression, Synaptic Facilitation and Long-Term Potentiation in the Hippocampus of Prion Mutant Mice

Background: Prionopathies are characterized by spongiform brain degeneration, myoclonia, dementia, and periodic electroencephalographic (EEG) disturbances. The hallmark of prioniopathies is the presence of an abnormal conformational isoform (PrP(sc)) of the natural cellular prion protein (PrP(c)) encoded by the Prnp gene. Although several roles have been attributed to PrP(c), its putative functions in neuronal excitability are unknown. Although early studies of the behavior of Prnp knockout mice described minor changes, later studies report altered behavior. To date, most functional PrP(c) studies on synaptic plasticity have been performed in vitro. To our knowledge, only one electrophysiological study has been performed in vivo in anesthetized mice, by Curtis and coworkers. They reported no significant differences in paired-pulse facilitation or LTP in the CA1 region after Schaffer collateral/commissural pathway stimulation. Principal Findings: Here we explore the role of PrP(c) expression in neurotransmission and neural excitability using wild-type, Prnp -/- and PrP(c)-overexpressing mice (Tg20 strain). By correlating histopathology with electrophysiology in living behaving mice, we demonstrate that both Prnp -/- mice but, more relevantly Tg20 mice show increased susceptibility to KA, leading to significant cell death in the hippocampus. This finding correlates with enhanced synaptic facilitation in paired-pulse experiments and hippocampal LTP in living behaving mutant mice. Gene expression profiling using Illumina microarrays and Ingenuity pathways analysis showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission were co-regulated in Prnp -/- and Tg20 mice. Lastly, RT-qPCR of neurotransmission-related genes indicated that subunits of GABA(A) and AMPA-kainate receptors are co-regulated in both Prnp -/- and Tg20 mice. Conclusions/Significance: Present results demonstrate that PrP(c) is necessary for the proper homeostatic functioning of hippocampal circuits, because of its relationships with GABA(A) and AMPA-Kainate neurotransmission. New PrP(c) functions have recently been described, which point to PrP(c) as a target for putative therapies in Alzheimer's disease. However, our results indicate that a "gain of function" strategy in Alzheimer's disease, or a "loss of function" in prionopathies, may impair PrP(c) function, with devastating effects. In conclusion, we believe that present data should be taken into account in the development of future therapies

Neurodevelopmental effects of undernutrition and placental underperfusion in fetal growth restriction rabbit models

Introduction: Chronic reduction of oxygen and nutrient delivery to the fetus has been related to neurodevelopmental problems. Placental underperfusion induces a significant reduction in oxygen and nutrient delivery, whereas maternal undernutrition causes mainly nutrient deficiency. A comparison of the neurodevelopmental effects of both situations in pregnant rabbits was performed. Materials and Methods: The placental underperfusion model was induced after uteroplacental vessel ligation at 25 days of pregnancy. The undernutrition model was induced after a reduction of 70% of the basal maternal intake at 22 days of pregnancy. Neurobehavioral tests were applied in the derived offspring at the neonatal period and over the long term. Structural brain differences were evaluated by brain networks obtained from diffusion magnetic resonance imaging. Results: Birth weight was significantly lower in both cases. However, stillbirth was only increased in the placental underperfusion model. Cases from both models presented poorer neurobehavioral performance and network infrastructure, being more pro-nounced in the placental underperfusion model. Discussion: Prenatal insults during the last third of gestation resulted in functional and structural disturbances. The degree of neurodevelopmental impairment and its association with structural brain reorganization seemed to be related to the type of the prenatal insult, showing stronger effects in the placental underperfusion model. (C) 2017 S. Karger AG, Base