A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

Neural plasticity associated with recently versus often heard objects.

In natural settings the same sound source is often heard repeatedly, with variations in spectro-temporal and spatial characteristics. We investigated how such repetitions influence sound representations and in particular how auditory cortices keep track of recently vs. often heard objects. A set of 40 environmental sounds was presented twice, i.e. as prime and as repeat, while subjects categorized the corresponding sound sources as living vs. non-living. Electrical neuroimaging analyses were applied to auditory evoked potentials (AEPs) comparing primes vs. repeats (effect of presentation) and the four experimental sections. Dynamic analysis of distributed source estimations revealed i) a significant main effect of presentation within the left temporal convexity at 164-215ms post-stimulus onset; and ii) a significant main effect of section in the right temporo-parietal junction at 166-213ms. A 3-way repeated measures ANOVA (hemisphere×presentation×section) applied to neural activity of the above clusters during the common time window confirmed the specificity of the left hemisphere for the effect of presentation, but not that of the right hemisphere for the effect of section. In conclusion, spatio-temporal dynamics of neural activity encode the temporal history of exposure to sound objects. Rapidly occurring plastic changes within the semantic representations of the left hemisphere keep track of objects heard a few seconds before, independent of the more general sound exposure history. Progressively occurring and more long-lasting plastic changes occurring predominantly within right hemispheric networks, which are known to code for perceptual, semantic and spatial aspects of sound objects, keep track of multiple exposures.

Anatomical exposure patterns of skin to sunlight: relative contributions of direct, diffuse and reflected ultraviolet radiation

Summary Background  The dose-response between ultraviolet (UV) exposure patterns and skin cancer occurrence is not fully understood. Sun-protection messages often focus on acute exposure, implicitly assuming that direct UV radiation is the key contributor to the overall UV exposure. However, little is known about the relative contribution of the direct, diffuse and reflected radiation components. Objective  To investigate solar UV exposure patterns at different body sites with respect to the relative contribution of the direct, diffuse and reflected radiation. Methods  A three-dimensional numerical model was used to assess exposure doses for various body parts and exposure scenarios of a standing individual (static and dynamic postures). The model was fed with erythemally weighted ground irradiance data for the year 2009 in Payerne, Switzerland. A year-round daily exposure (08:00-17:00 h) without protection was assumed. Results  For most anatomical sites, mean daily doses were high (typically 6·2-14·6 standard erythemal doses) and exceeded the recommended exposure values. Direct exposure was important during specific periods (e.g. midday during summer), but contributed moderately to the annual dose, ranging from 15% to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose. Acute diffuse exposures were also observed during cloudy summer days. Conclusions  The importance of diffuse UV radiation should not be underestimated when advocating preventive measures. Messages focused on avoiding acute direct exposures may be of limited efficiency to prevent skin cancers associated with chronic exposure.

Neurophysiologic and proteomic investigations of experience-dependent plasticity in the somatosensory cortex of the adult mouse following chronic whisker stimulation

RESUME Les follicules des vibrisses des rongeurs sont représentés sous la forme d'une carte topographique dans le cortex à tonneaux. Lorsque un groupe de vibrisses est coupé pendant plusieurs jours chez un rongeur adulte, en laissant les autres vibrisses intactes, le champ réceptif des neurones du cortex à tonneaux est modifié, ce qui démontre que les cartes corticales sont plastiques. Dans notre étude, une expérience sensorielle a été induite chez une souris adulte se comportant librement en stimulant chroniquement une de ses vibrisses pendant 24h. Par une analyse des potentiels de champ locaux, nous démontrons que les caractéristiques spatiotemporelles du flux d'excitation évoqué par la vibrisse principale (VP) dans la colonne corticale correspondante à la vibrisse stimulée n'est pas altéré. Par contre, l'enregistrement des potentiels d'actions d'un total de 1041 neurones à travers le cortex à tonneaux révèlent plusieurs modifications de l'activité neuronale. L'activité spontanée ainsi que la réponse évoquée par la VP sont déprimées dans la colonne corticale stimulée (nombre moyen de potentiels d'action évoqués par la VP diminue de 25 % et 36% dans la couche IV et les couches II&III). La réponse des neurones à la vibrisse stimulée diminue également dans les colonnes corticales adjacentes, «non-stimulées». La dépression de l'activité spontanée et de la réponse à la VP est localisée à la colonne corticale stimulée. Dans le tonneau stimulé, la première partie de la réponse à la VP n'est pas affaiblie, démontrant que la dépression de la réponse n'est pas due à un phénomène de plasticité sous-corticale ou thalamocorticale. La stimulation chronique d'une vibrisse entraîne une augmentation du nombre de synapses GABAergiques dans la couche IV du tonneau correspondant (Knott et al, 2002). Dès lors, nos résultats suggèrent qu'une augmentation de l'inhibition dans le tonneau stimulé serait à l'origine de la diminution des potentiels d'action évoqués par la vibrisse stimulée et en conséquence de l'amplitude du flux d'excitation vers les couches II&III puis vers les colonnes corticales adjacentes. Toutes les réponses des neurones du tonneau stimulé ne sont pas déprimées. Les réponses des neurones à la vibrisse voisine caudale à VP diminuent dans la couche IV (42%) et dans les couches II&III (52%) mais pas les réponses aux 7 autres vibrisses voisines. Les entrées synaptiques en provenance de la vibrisse caudale pourraient avoir été spécifiquement déprimées en raison d'une décorrélation prolongée entre l'activité évoquée dans les chemins sensoriels relatifs à la vibrisse stimulée et à la vibrisse caudale, spécificité qui découlerait du fait que, parmi les vibrisses voisines à la VP, la vibrisse caudale génère les réponses les plus fortes dans la colonne corticale. Quatre jours après l'arrêt de la stimulation, l'activité neuronale n'est plus déprimée; au contraire, nous observons une potentiation des réponses à la VP dans la couche IV de la colonne corticale stimulée. De plus, nous montrons que l'expression des protéines GLT-1 et GLAST, deux transporteurs astrocytaires du glutamate, est augmentée de ~2.5 fois dans la colonne corticale stimulée, indiquant l'existence d'une «plasticité gliale» et suggérant que les cellules gliales participent activement à l'adaptation du cerveau à l'expérience. ABSTRACT In the barrel cortex, mystacial whisker follicles are represented in the form of a topographie map. The selective removal of a set of whiskers while sparing others for several days in an adult rodent alters receptive field of barrel cortex neurons, demonstrating experience-dependent plasticity of cortical maps. Here sensory experience was altered by chronic stimulation of a whisker for a 24h period in a freely behaving adult mouse. By means of an evoked local field potential analysis, we show that chronic stimulation does not alter the flow of excitation evoked by the principal whisker (PW) in the stimulated barrel column. However, the recording of neuronal firing from a total of 1041 single units throughout the barrel cortex reveals several changes in neuronal activity. Immediately after chronic stimulation, spontaneous activity as well as PW-responses are depressed in the stimulated barrel column (mean number of spikes per PW-deflection decreases by 25% and 36% in layer IV and layers II&III, respectively). Neuronal responses towards the chronically stimulated whisker are also significantly depressed in layers II&III of the adjacent "non-stimulated" barrel' columns. The depression of both spontaneous activity and PW-responses are restricted to the stimulated ban-el column. The earliest time epoch of the PW-response in the stimulated barrel is not depressed, demonstrating that the decrease of cortical responses is not due to subcortical or thalamocortical plasticity. The depression of PW-response in the stimulated barrel correlates with an increase in the number of GABAergic synapses in layer IV (Knott et al., 2002). Therefore, our results suggest that an increase in inhibition within the stimulated barrel may reduce its excitatory output and accordingly the flow of excitation towards layers and the subsequent horizontal spread into adjacent barrel columns. Not all responses of neurons in the stimulated barrel are depressed. Neuronal responses towards the caudal in-row whisker decrease by 42% in layer IV and 52% in layers MM but responses to the other 7 immediate surround whiskers (SWs) are not affected. The synaptic inputs from the SW that elicit the strongest responses in the stimulated barrel may have been specifically depressed following a prolonged period of diminished coherence between neuronal activity evoked in the pathways from the chronically stimulated whisker and from its surrounding in-row whisker. Four days after the cessation of the stimulation, depression of neuronal activity is no longer present; on the contrary, we observe a small but significant potentiation of PW-responses in layer IV of the stimulated barrel column. Moreover we show that the expression of astrocytic glutamate transporters GLT-1 and GLAST proteins were both upregulated by ~2.5 fold in the stimulated barrel column, which indicates that glial cells exhibit experience-dependent functional changes and could actively take part in the adaptation of the cerebral cortex to experience.

Emergence of oriented circuits driven by synaptic pruning associated with spike-timing-dependent plasticity (STDP)

ABSTRACT: Massive synaptic pruning following over-growth is a general feature of mammalian brain maturation. Pruning starts near time of birth and is completed by time of sexual maturation. Trigger signals able to induce synaptic pruning could be related to dynamic functions that depend on the timing of action potentials. Spike-timing-dependent synaptic plasticity (STDP) is a change in the synaptic strength based on the ordering of pre- and postsynaptic spikes. The relation between synaptic efficacy and synaptic pruning suggests that the weak synapses may be modified and removed through competitive "learning" rules. This plasticity rule might produce the strengthening of the connections among neurons that belong to cell assemblies characterized by recurrent patterns of firing. Conversely, the connections that are not recurrently activated might decrease in efficiency and eventually be eliminated. The main goal of our study is to determine whether or not, and under which conditions, such cell assemblies may emerge out of a locally connected random network of integrate-and-fire units distributed on a 2D lattice receiving background noise and content-related input organized in both temporal and spatial dimensions. The originality of our study stands on the relatively large size of the network, 10,000 units, the duration of the experiment, 10E6 time units (one time unit corresponding to the duration of a spike), and the application of an original bio-inspired STDP modification rule compatible with hardware implementation. A first batch of experiments was performed to test that the randomly generated connectivity and the STDP-driven pruning did not show any spurious bias in absence of stimulation. Among other things, a scale factor was approximated to compensate for the network size on the ac¬tivity. Networks were then stimulated with the spatiotemporal patterns. The analysis of the connections remaining at the end of the simulations, as well as the analysis of the time series resulting from the interconnected units activity, suggest that feed-forward circuits emerge from the initially randomly connected networks by pruning. RESUME: L'élagage massif des synapses après une croissance excessive est une phase normale de la ma¬turation du cerveau des mammifères. L'élagage commence peu avant la naissance et est complété avant l'âge de la maturité sexuelle. Les facteurs déclenchants capables d'induire l'élagage des synapses pourraient être liés à des processus dynamiques qui dépendent de la temporalité rela¬tive des potentiels d'actions. La plasticité synaptique à modulation temporelle relative (STDP) correspond à un changement de la force synaptique basé sur l'ordre des décharges pré- et post- synaptiques. La relation entre l'efficacité synaptique et l'élagage des synapses suggère que les synapses les plus faibles pourraient être modifiées et retirées au moyen d'une règle "d'appren¬tissage" faisant intervenir une compétition. Cette règle de plasticité pourrait produire le ren¬forcement des connexions parmi les neurones qui appartiennent à une assemblée de cellules caractérisée par des motifs de décharge récurrents. A l'inverse, les connexions qui ne sont pas activées de façon récurrente pourraient voir leur efficacité diminuée et être finalement éliminées. Le but principal de notre travail est de déterminer s'il serait possible, et dans quelles conditions, que de telles assemblées de cellules émergent d'un réseau d'unités integrate-and¬-fire connectées aléatoirement et distribuées à la surface d'une grille bidimensionnelle recevant à la fois du bruit et des entrées organisées dans les dimensions temporelle et spatiale. L'originalité de notre étude tient dans la taille relativement grande du réseau, 10'000 unités, dans la durée des simulations, 1 million d'unités de temps (une unité de temps correspondant à une milliseconde), et dans l'utilisation d'une règle STDP originale compatible avec une implémentation matérielle. Une première série d'expériences a été effectuée pour tester que la connectivité produite aléatoirement et que l'élagage dirigé par STDP ne produisaient pas de biais en absence de stimu¬lation extérieure. Entre autres choses, un facteur d'échelle a pu être approximé pour compenser l'effet de la variation de la taille du réseau sur son activité. Les réseaux ont ensuite été stimulés avec des motifs spatiotemporels. L'analyse des connexions se maintenant à la fin des simulations, ainsi que l'analyse des séries temporelles résultantes de l'activité des neurones, suggèrent que des circuits feed-forward émergent par l'élagage des réseaux initialement connectés au hasard.

Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence.

Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic-pituitary-gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticity. However, the mechanisms that regulate this plasticity are still largely unknown. We demonstrate that Semaphorin7A, expressed by tanycytes, plays a dual role, inducing the retraction of GnRH terminals and promoting their ensheathment by tanycytic end feet via the receptors PlexinC1 and Itgb1, respectively. Moreover, Semaphorin7A expression is regulated during the oestrous cycle by the fluctuating levels of gonadal steroids. Genetic invalidation of Semaphorin7A receptors in mice induces neuronal and glial rearrangements in the ME and abolishes normal oestrous cyclicity and fertility. These results show a role for Semaphorin7A signalling in mediating periodic neuroglial remodelling in the adult ME during the ovarian cycle.

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons.

BACKGROUND: Oxidative stress and the specific impairment of perisomatic gamma-aminobutyric acid circuits are hallmarks of the schizophrenic brain and its animal models. Proper maturation of these fast-spiking inhibitory interneurons normally defines critical periods of experience-dependent cortical plasticity. METHODS: Here, we linked these processes by genetically inducing a redox dysregulation restricted to such parvalbumin-positive cells and examined the impact on critical period plasticity using the visual system as a model (3-6 mice/group). RESULTS: Oxidative stress was accompanied by a significant loss of perineuronal nets, which normally enwrap mature fast-spiking cells to limit adult plasticity. Accordingly, the neocortex remained plastic even beyond the peak of its natural critical period. These effects were not seen when redox dysregulation was targeted in excitatory principal cells. CONCLUSIONS: A cell-specific regulation of redox state thus balances plasticity and stability of cortical networks. Mistimed developmental trajectories of brain plasticity may underlie, in part, the pathophysiology of mental illness. Such prolonged developmental plasticity may, in turn, offer a therapeutic opportunity for cognitive interventions targeting brain plasticity in schizophrenia.

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

INTRODUCTION: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Micrornas involvement in cortical plasticity in adult mouse barrel cortex

In rodents, sensory experience alters the whisker representation in layer IV of the barrel cortex (Woolsey and Van der Loos, 1970). Excitatory and inhibitory interneurons, together with the astrocytic network, modify the functional representation in an integrated manner. Our group showed that continuous whisker stimulation induces structural and functional changes in the corresponding barrel. These modifications include the depression of neuronal responses and an insertion of new inhibitory synapses on dendritic spines (Knott et al., 2002; Genoud et al., 2006; Quairiaux et al., 2007). This form of cortical plasticity is controlled by several gene regulatory mechanisms including the activation of genetic programs controlling the expression of microRNAs (miRNAs). The transitory and localized expression of miRNAs in dendrites and their capacity to respond in an activity-dependent manner make them ideal candidates for the fine tuning of gene expression associated with neural plasticity. In a previous study of our group (Johnston- Wenger, 2010) using microarray analysis on laser-dissected barrels in order to compare the gene expression levels in stimulated and non-stimulated barrels after whisker stimulation, 261 genes were found significantly regulated, among these genes there were two miRNAs (miR- 132 and miR-137). In this study I tested the initial observation on the up-regulation of miR-132 and miR-137 after whisker stimulation and the possible involvement of two other miRNAs (miR-138 and miR-125b) that are known play a role in other form of synaptic plasticity. I used in situ hybridization (ISH) after unilateral stimulation of three whiskers (Cl-3) in the adult mouse. We found that sensory stimulation increases the expression, of miR-132 after 3hours of stimulation (p<0.01) and miR-137 (pO.Ol; 24 hrs of stim.), whereas it reduces the level of miR-125b (pO.Ol; 9 hrs of stim.). No significant difference was detected for miR-138. We further determined a correlation between the level of expression of the four selected miRNAs in the cortical barrels (measured by ISH) and in blood plasma (measured by qPCR). In addition to this quantitative comparison, we combined miRNAs ISH and immunolabeling for various neuronal markers that were chosen for the localization in both excitatory and inhibitory circuits as well as in astrocytes. Analysis of three-dimensional confocal acquisitions showed that stimulation alters significantly the degree of co-localization in the stimulated barrel of miR-132 with GAD65/67 and VGLUT2; miR-125b with GAD65/67 and parvalbumin; miR-138 with parvalbumin, VGLUT1 and PSD95; and miR-137 with VGLUT1 and astrocytic markers (GS; GFAP and SlOOß). To conclude, using increased neuronal activity in the whisker-to-barrel pathway; our results suggest that miRNAs can be regulated in an activity-dependent manner and they may regulate local mRNA translation to shape neuronal responses. These findings motivate further investigation of the different modes in which miRNAs may regulate cortical plasticity. -- Chez les rongeurs, l'expérience sensorielle modifie la représentation des vibrisses au niveau du cortex somatosensoriel primaire (Woolsey and Van der Loos, 1970). Les interneurones excitateurs et inhibiteurs, en collaboration avec le réseau astrocytaire, modifient la représentation fonctionnelle d'une manière intégrée. Notre groupe a montré que la stimulation continue des vibrisses induit des changements structuraux et fonctionnels dans le tonneau correspondant. Ces modifications incluent la dépression des réponses neuronales et une insertion de nouvelles synapses inhibitrices sur les épines dendritiques (Knott et al., 2002 ; Genoud et al., 2006 ; Quairiaux et al., 2007). Cette forme de plasticité corticale est contrôlée par plusieurs mécanismes de régulation génique dont l'activation des programmes géniques contrôlant l'expression des microARNs (miARNs). Par leur expression transitoire et localisée dans les dendrites et leur capacité à réagir d'une manière dépendante de l'activité, les miARNs sont des candidats idéaux pour le réglage fin de l'expression des gènes associée à la plasticité neuronale. Afin de comparer le niveau d'expression des gènes dans les tonneaux stimulés et non-stimulés après stimulation des vibrisses, une étude antérieure dans notre groupe (Johnston-Wenger, 2010), utilisant l'analyse par microarray sur des tonneaux disséqués par laser, a montré l'altération significative de 261 gènes. Parmi ces gènes, il y avait deux miARNs (miR-132 et miR-137). Dans la présente étude, j'ai testé l'observation initiale sur la régulation de miR-132 et miR-137 après stimulation des vibrisses et la possible implication de deux autres miARNs (miR-138 et miR-125b) connus avoir jouer un rôle important dans d'autres formes de plasticité synaptique. J'ai utilisé l'hybridation in situ (ISH) après stimulation unilatérale de trois vibrisses (Cl-3) chez la souris adulte. J'ai trouvé que la stimulation sensorielle augmente l'expression, de miR-132 après 3 heures de stimulation (p < 0.01) et miR-137 (p < 0.01 ; 24 hrs de stim.), alors qu'elle réduit le niveau de miR-125b (p < 0.01; 9 hrs de stim.). Aucune différence significative n'a été détectée pour miR-138. J'ai aussi déterminé une corrélation entre le niveau d'expression des quatre miARNs sélectionnés dans les tonneaux (mesurés par ISH) et dans le plasma sanguin (mesuré par qPCR). En plus de cette comparaison quantitative, j'ai combiné le miR-ISH et l'immunomarquage pour divers marqueurs neuronaux qui ont été choisis pour étudier la localisation dans les circuits excitateurs et inhibiteurs, ainsi que dans les astrocytes. Les acquisitions tridimensionnelles montrent que la stimulation modifie considérablement le degré de co-localisation dans le tonneau stimulé de miR-132 avec GAD65/67 et VGLUT2; miR-125b avec GAD65/67 et parvalbumine; miR-138 avec parvalbumine, VGLUT1 et PSD95; et miR-137 avec VGLUT1 et les marqueurs astrocytaires (GS ; GFAP et SlOOß). En conclusion, à l'aide de l'activité neuronale accrue dans la voie de vibrisses-au-baril; les résultats suggèrent que les miARNs peuvent être régulé d'une manière dépendante de l'activité et peuvent résulter la stabilité des ARNm et la traduction pour façonner les réponses neuronales ultérieures. Ces résultats incitent d'investiguer davantage les voies importantes par lesquels les miARNs peuvent réguler la plasticité corticale.