Gut microbiota: A potential regulator of neurodevelopment

During childhood, our brain is exposed to a variety of environmental inputs that can sculpt synaptic connections and neuronal circuits, with subsequent influence on behavior and learning processes. Critical periods of neurodevelopment are windows of opportunity in which the neuronal circuits are extremely plastic and can be easily subjected to remodeling in response to experience. However, the brain is also more susceptible to aberrant stimuli that might lead to altered developmental trajectories. Intriguingly, postnatal brain development is paralleled by the maturation of the gut microbiota: the ecosystem of symbionts populating our gastro-intestinal tract. Recent discoveries have started to unveil an unexpected link between the gut microbiome and neurophysiological processes. Indeed, the commensal bacteria seem to be able to influence host behavioral outcome and neurochemistry through mechanisms which remain poorly understood. Remarkably, the efficacy of the gut flora action appears to be dependent on the timing during postnatal life at which the host gut microbes' signals reaches the brain, suggesting the fascinating possibility of critical periods for this microbiota-driven shaping of host neuronal functions and behavior. Therefore, to understand the importance of the intestinal ecosystem's impact on neuronal circuits functions and plasticity during development and the discovery of the involved molecular mechanisms, will pave the way to identify new and, hopefully, powerful microbiota-based therapeutic interventions for the treatment of neurodevelopmental and psychiatric diseases

Cocaine-mediated circadian reprogramming in the striatum through dopamine D2R and PPARγ activation

Substance abuse disorders are linked to alteration of circadian rhythms, although the molecular and neuronal pathways implicated have not been fully elucidated. Addictive drugs, such as cocaine, induce a rapid increase of dopamine levels in the brain. Here, we show that acute administration of cocaine triggers reprogramming in circadian gene expression in the striatum, an area involved in psychomotor and rewarding effects of drugs. This process involves the activation of peroxisome protein activator receptor gamma (PPARγ), a nuclear receptor involved in inflammatory responses. PPARγ reprogramming is altered in mice with cell-specific ablation of the dopamine D2 receptor (D2R) in the striatal medium spiny neurons (MSNs) (iMSN-D2RKO). Administration of a specific PPARγ agonist in iMSN-D2RKO mice elicits substantial rescue of cocaine-dependent control of circadian genes. These findings have potential implications for development of strategies to treat substance abuse disorders

Capacitance-conductance investigation on the phase transitions in Ga nanoparticles

We have reported on coupled capacitance-conductance measurements on Ga nanoparticles embedded in vitreous matrices. The melting of nanoparticles was clearly detected as an abrupt increase in the capacitance vs. temperature scans. The influence of the embedding matrix and of the frequency of the applied field on the dielectric response was checked. The presence of a hysteresis cycle between melting and solidification has been detected. The technique allows the identification of the various solid phases of confined Ga

Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception

MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception

Electronic states and optical properties of GaAs/AlAs and GaAs/vacuum superlattices by the linear combination of bulk bands method

The linear combination of bulk bands method recently introduced by Wang, Franceschetti and Zunger [Phys. Rev. Lett.78, 2819 (1997)] is applied to a calculation of energy bands and optical constants of (GaAs)$_n$/(AlAs)$_n$ and (GaAs)$_n$/(vacuum)$_n$ (001) superlattices with n ranging from 4 to 20. Empirical pseudopotentials are used for the calculation of the bulk energy bands. Quantum-confined induced shifts of critical point energies are calculated and are found to be larger for the GaAs/vacuum system. The $E_1$ peak in the absorption spectra has a blue shift and splits into two peaks for decreasing superlattice period; the $E_2$ transition instead is found to be split for large-period GaAs/AlAs superlattices. The band contribution to linear birefringence of GaAs/AlAs superlattices is calculated and compared with recent experimental results of Sirenko et al. [Phys. Rev. B 60, 8253 (1999)]. The frequency-dependent part reproduces the observed increase with decreasing superlattice period, while the calculated zero-frequency birefringence does not account for the experimental results and points to the importance of local-field effects.Comment: 10 pages, 11 .eps figures, 1 tabl

Theoretical study of the insulating oxides and nitrides: SiO2, GeO2, Al2O3, Si3N4, and Ge3N4

An extensive theoretical study is performed for wide bandgap crystalline oxides and nitrides, namely, SiO_{2}, GeO_{2}, Al_{2}O_{3}, Si_{3}N_{4}, and Ge_{3}N_{4}. Their important polymorphs are considered which are for SiO_{2}: $\alpha$-quartz, $\alpha$- and $\beta$-cristobalite and stishovite, for GeO_{2}: $\alpha$-quartz, and rutile, for Al_{2}O_{3}: $\alpha$-phase, for Si_{3}N_{4} and Ge_{3}N_{4}: $\alpha$- and $\beta$-phases. This work constitutes a comprehensive account of both electronic structure and the elastic properties of these important insulating oxides and nitrides obtained with high accuracy based on density functional theory within the local density approximation. Two different norm-conserving \textit{ab initio} pseudopotentials have been tested which agree in all respects with the only exception arising for the elastic properties of rutile GeO_{2}. The agreement with experimental values, when available, are seen to be highly satisfactory. The uniformity and the well convergence of this approach enables an unbiased assessment of important physical parameters within each material and among different insulating oxide and nitrides. The computed static electric susceptibilities are observed to display a strong correlation with their mass densities. There is a marked discrepancy between the considered oxides and nitrides with the latter having sudden increase of density of states away from the respective band edges. This is expected to give rise to excessive carrier scattering which can practically preclude bulk impact ionization process in Si_{3}N_{4} and Ge_{3}N_{4}.Comment: Published version, 10 pages, 8 figure

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

MiR-29 coordinates age-dependent plasticity brakes in the adult visual cortex

Visual cortical circuits show profound plasticity during early life and are later stabilized by molecular “brakes” limiting excessive rewiring beyond a critical period. The mechanisms coordinating the expression of these factors during the transition from development to adulthood remain unknown. We found that miR‐29a expression in the visual cortex dramatically increases with age, but it is not experience‐dependent. Precocious high levels of miR‐29a blocked ocular dominance plasticity and caused an early appearance of perineuronal nets. Conversely, inhibition of miR‐29a in adult mice using LNA antagomirs activated ocular dominance plasticity, reduced perineuronal nets, and restored their juvenile chemical composition. Activated adult plasticity had the typical functional and proteomic signature of critical period plasticity. Transcriptomic and proteomic studies indicated that miR‐29a manipulation regulates the expression of plasticity brakes in specific cortical circuits. These data indicate that miR‐29a is a regulator of the plasticity brakes promoting age‐dependent stabilization of visual cortical connections

miR-212/132 expression and functions: within and beyond the neuronal compartment

During the last two decades, microRNAs (miRNAs) emerged as critical regulators of gene expression. By modulating the expression of numerous target mRNAs mainly at the post-transcriptional level, these small non-coding RNAs have been involved in most, if not all, biological processes as well as in the pathogenesis of a number of diseases. miR-132 and miR-212 are tandem miRNAs whose expression is necessary for the proper development, maturation and function of neurons and whose deregulation is associated with several neurological disorders, such as Alzheimer's disease and tauopathies (neurodegenerative diseases resulting from the pathological aggregation of tau protein in the human brain). Although their involvement in neuronal functions is the most described, evidences point towards a role of these miRNAs in many other biological processes, including inflammation and immune functions. Incidentally, miR-132 was recently classified as a ‘neurimmiR’, a class of miRNAs operating within and between the neural and immune compartments. In this review, we propose an outline of the current knowledge about miR-132 and miR-212 functions in neurons and immune cells, by describing the signalling pathways and transcription factors regulating their expression as well as their putative or demonstrated roles and validated mRNA targets

Carrier multiplication in germanium nanocrystals

Carrier multiplication is demonstrated in a solid-state dispersion of germanium nanocrystals in a silicon-dioxide matrix. This is performed by comparing ultrafast photo-induced absorption transients at different pump photon energies below and above the threshold energy for this process. The average germanium nanocrystal size is approximately 5-6 nm, as inferred from photoluminescence and Raman spectra. A carrier multiplication efficiency of approximately 190% is measured for photo-excitation at 2.8 times the optical bandgap of germanium nanocrystals, deduced from their photoluminescence spectra.Foundation for Fundamental Research on Matter (FOM)info:eu-repo/semantics/publishedVersio