Harnessing the Natural Resonances of Time-Varying Dispersive Interfaces.

Space-time modulation of electromagnetic parameters offers novel exciting possibilities for advanced field manipulations. In this study, we explore wave scattering from a time-varying interface characterized by a Lorentz-type dispersion with a steplike temporal variation in its parameters. Our findings reveal a new process: an unconventional frequency generation at the natural resonances of the system.

Integrative multi-omic analysis reveals conserved cell-projection deficits in human Down syndrome brains.

Down syndrome (DS) is the most common genetic cause of cognitive disability. However, it is largely unclear how triplication of a small gene subset may impinge on diverse aspects of DS brain physiopathology. Here, we took a multi-omic approach and simultaneously analyzed by RNA-seq and proteomics the expression signatures of two diverse regions of human postmortem DS brains.

Heterogeneous subpopulations of GABAR-responding neurons coexist across neuronal network scales and developmental stages in health and disease.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adults. Depolarizing GABA responses have been well characterized at neuronal-population level during typical neurodevelopment and partially in brain disorders. However, no investigation has specifically assessed whether a of cells with either depolarizing or hyperpolarizing/inhibitory GABAergic responses exists in animals in health/disease at diverse developmental stages, including adulthood.

Morphology Effects on Electro- and Photo-Catalytic Properties of Zinc Oxide Nanostructures.

Environmental problems are among the most pressing issues in the modern world, including the shortage of clean drinking water partially caused by contamination from various industries and the excessive emission of CO primarily from the massive use of fossil fuels. Consequently, it is crucial to develop inexpensive, effective, and environmentally friendly methods for wastewater treatment and CO reduction, turning them into useful feedstocks. This study explores a unique method that addresses both challenges by utilizing ZnO, which is recognized as one of the most active semiconductors for photocatalysis, as well as a cost-effective electrocatalyst for the CO reduction reaction (CORR).

Shank3 deficits in the anteromedial bed nucleus of the stria terminalis trigger an anxiety phenotype in mice.

Anxiety disorders are the most prevalent co-morbidity factor associated with the core domains of autism spectrum disorders (ASD). Investigations on potential common neuronal mechanisms that may explain the co-occurrence of ASD and anxiety disorders are still poorly explored. One of the key questions that remained unsolved is the role of Shank3 protein in anxiety behaviours.

LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice.

Spinobulbar muscular atrophy (SBMA) is caused by CAG expansions in the androgen receptor gene. Androgen binding to polyQ-expanded androgen receptor triggers SBMA through a combination of toxic gain-of-function and loss-of-function mechanisms. Leveraging cell lines, mice, and patient-derived specimens, we show that androgen receptor co-regulators lysine-specific demethylase 1 (LSD1) and protein arginine methyltransferase 6 (PRMT6) are overexpressed in an androgen-dependent manner specifically in the skeletal muscle of SBMA patients and mice.

Oxytocin neurons mediate the effect of social isolation via the VTA circuits.

Social interaction during adolescence strongly influences brain function and behavior, and the recent pandemic has emphasized the devastating effect of social distancing on mental health. While accumulating evidence has shown the importance of the reward system in encoding specific aspects of social interaction, the consequences of social isolation on the reward system and the development of social skills later in adulthood are still largely unknown. Here, we found that 1 week of social isolation during adolescence in male mice increased social interaction at the expense of social habituation and social novelty preference.

Superior Colliculus to VTA pathway controls orienting response and influences social interaction in mice.

Social behaviours characterize cooperative, mutualistic, aggressive or parental interactions that occur among conspecifics. Although the Ventral Tegmental Area (VTA) has been identified as a key substrate for social behaviours, the input and output pathways dedicated to specific aspects of conspecific interaction remain understudied. Here, in male mice, we investigated the activity and function of two distinct VTA inputs from superior colliculus (SC-VTA) and medial prefrontal cortex (mPFC-VTA).

Inhibition of Trpv4 rescues circuit and social deficits unmasked by acute inflammatory response in a Shank3 mouse model of Autism.

Mutations in the SHANK3 gene have been recognized as a genetic risk factor for Autism Spectrum Disorder (ASD), a neurodevelopmental disease characterized by social deficits and repetitive behaviors. While heterozygous SHANK3 mutations are usually the types of mutations associated with idiopathic autism in patients, heterozygous deletion of Shank3 gene in mice does not commonly induce ASD-related behavioral deficit. Here, we used in-vivo and ex-vivo approaches to demonstrate that region-specific neonatal downregulation of Shank3 in the Nucleus Accumbens promotes D1R-medium spiny neurons (D1R-MSNs) hyperexcitability and upregulates Transient Receptor Potential Vanilloid 4 (Trpv4) to impair social behavior.

Ground-State Properties and Phase Separation of Binary Mixtures in Mesoscopic Ring Lattices.

We investigated the spatial phase separation of the two components forming a bosonic mixture distributed in a four-well lattice with a ring geometry. We studied the ground state of this system, described by means of a binary Bose-Hubbard Hamiltonian, by implementing a well-known coherent-state picture which allowed us to find the semi-classical equations determining the distribution of boson components in the ring lattice. Their fully analytic solutions, in the limit of large boson numbers, provide the boson populations at each well as a function of the interspecies interaction and of other significant model parameters, while allowing to reconstruct the non-trivial architecture of the ground-state four-well phase diagram.

Design, Synthesis, and Characterization of Selective NKCC1 Inhibitors for the Treatment of Core Symptoms in Down Syndrome.

Intracellular chloride concentration [Cl] is defective in several neurological disorders. In neurons, [Cl] is mainly regulated by the action of the Na-K-Cl importer NKCC1 and the K-Cl exporter KCC2. Recently, we have reported the discovery of as the lead candidate of a novel class of selective inhibitors of NKCC1.

Restoring neuronal chloride homeostasis with anti-NKCC1 gene therapy rescues cognitive deficits in a mouse model of Down syndrome.

A common feature of diverse brain disorders is the alteration of GABA-mediated inhibition because of aberrant, intracellular chloride homeostasis induced by changes in the expression and/or function of chloride transporters. Notably, pharmacological inhibition of the chloride importer NKCC1 is able to rescue brain-related core deficits in animal models of these pathologies and in some human clinical studies. Here, we show that reducing NKCC1 expression by RNA interference in the Ts65Dn mouse model of Down syndrome (DS) restores intracellular chloride concentration, efficacy of gamma-aminobutyric acid (GABA)-mediated inhibition, and neuronal network dynamics in vitro and ex vivo.

Deconstructing the contribution of sensory cues in social approach.

Social interaction is a complex and highly conserved behavior that safeguards survival and reproductive success. Although considerable progress has been made regarding our understanding of same-sex conspecific and non-aggressive interactions, questions regarding the precise contribution of sensory cues in social approach and their specific neurobiological correlates remain open. Here, by designing a series of experiments with diverse social and object stimuli manipulations in custom-made enclosures, we first sought to deconstruct key elements of social preference as assessed by the three-chamber task.

Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome.

Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile.

Variable Interhemispheric Asymmetry in Layer V of the Supplementary Motor Area following Cervical Hemisection in Adult Macaque Monkeys.

Motor cortical areas from both hemispheres play a role during functional recovery after a unilateral spinal cord injury (SCI). However, little is known about the morphologic and phenotypical differences that a SCI could trigger in corticospinal (CS) neurons of the ipsilesional and contralesional hemisphere. Using an SMI-32 antibody which specifically labeled pyramidal neurons in cortical Layers V, we investigated the impact of a unilateral cervical cord lesion on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres of eight adult macaque monkeys compared with four intact control monkeys.

Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders.

Aberrant expression ratio of Cl transporters, NKCC1 and KCC2, is implicated in several brain conditions. NKCC1 inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms in rodent models and/or clinical trials with patients. However, bumetanide has a strong diuretic effect due to inhibition of the kidney Cl transporter NKCC2, creating critical drug compliance issues and health concerns.

Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex.

Erythropoietin (EPO), the hypoxia-inducible hematopoietic hormone, has well-established neuroprotective/neurotrophic roles in the developing central nervous system and the therapeutic potential of EPO has been widely explored in clinical studies for the treatment of perinatal hypoxic brain lesion, as well as prematurity. Here, we reveal that both EPO and Epo receptor (EPOR) are expressed in the developing rat somatosensory cortex during radial migration and laminar positioning of granular and supragranular neurons. Experimental deregulation of EPO signaling using genetic approaches results in aberrant migration, as well as permanent neuronal misplacement leading to abnormal network activity and protracted sensory behavioral deficits.

Transplanted Embryonic Neurons Improve Functional Recovery by Increasing Activity in Injured Cortical Circuits.

Transplantation of appropriate neuronal precursors after injury is a promising strategy to reconstruct cortical circuits, but the efficiency of these approaches remains limited. Here, we applied targeted apoptosis to selectively ablate layer II/III pyramidal neurons in the rat juvenile cerebral cortex and attempted to replace lost neurons with their appropriate embryonic precursors by transplantation. We demonstrate that grafted precursors do not migrate to replace lost neurons but form vascularized clusters establishing reciprocal synaptic contacts with host networks and show functional integration.

Gene Editing Preserves Visual Functions in a Mouse Model of Retinal Degeneration.

Inherited retinal dystrophies (IRDs) are a large and heterogeneous group of degenerative diseases caused by mutations in various genes. Given the favorable anatomical and immunological characteristics of the eye, gene therapy holds great potential for their treatment. Our goal is to validate the preservation of visual functions by viral-free homology directed repair (HDR) in an autosomal recessive loss of function mutation.

Synapsin I Synchronizes GABA Release in Distinct Interneuron Subpopulations.

Neurotransmitters can be released either synchronously or asynchronously with respect to action potential timing. Synapsins (Syns) are a family of synaptic vesicle (SV) phosphoproteins that assist gamma-aminobutyric acid (GABA) release and allow a physiological excitation/inhibition balance. Consistently, deletion of either or both Syn1 and Syn2 genes is epileptogenic.

SINEUP Non-coding RNA Targeting GDNF Rescues Motor Deficits and Neurodegeneration in a Mouse Model of Parkinson's Disease.

Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the treatment of Parkinson's disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression.

Corticotectal Projections From the Premotor or Primary Motor Cortex After Cortical Lesion or Parkinsonian Symptoms in Adult Macaque Monkeys: A Pilot Tracing Study.

The corticotectal projections, together with the corticobulbar (corticoreticular) projections, work in parallel with the corticospinal tract (CST) to influence motoneurons in the spinal cord both directly and indirectly the brainstem descending pathways. The tectospinal tract (TST) originates in the deep layers of the superior colliculus. In the present study, we analyzed the corticotectal projections from two motor cortical areas, namely the premotor cortex (PM) and the primary motor cortex (M1) in eight macaque monkeys subjected to either a cortical lesion of the hand area in M1 ( = 4) or Parkinson's disease-like symptoms PD ( = 4).

Transient Deregulation of Canonical Wnt Signaling in Developing Pyramidal Neurons Leads to Dendritic Defects and Impaired Behavior.

During development, the precise implementation of molecular programs is a key determinant of proper dendritic development. Here, we demonstrate that canonical Wnt signaling is active in dendritic bundle-forming layer II pyramidal neurons of the rat retrosplenial cortex during dendritic branching and spine formation. Transient downregulation of canonical Wnt transcriptional activity during the early postnatal period irreversibly reduces dendritic arbor architecture, leading to long-lasting deficits in spatial exploration and/or navigation and spatial memory in the adult.