Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons.

Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses, and thereby translate information about the external environment into internal neuronal representations. This retrograde signaling is critical to dendritic growth, synapse development, and neuronal plasticity. Here, we demonstrate that neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor APPL1.

Microglia in depression: current perspectives.

Major depressive disorder (MDD) is a prevalent psychiatric disease that involves malfunctions of different cell types in the brain. Accumulating studies started to reveal that microglia, the primary resident immune cells, play an important role in the development and progression of depression. Microglia respond to stress-triggered neuroinflammation, and through the release of proinflammatory cytokines and their metabolic products, microglia may modulate the function of neurons and astrocytes to regulate depression.

Sex differences in stress-related disorders: Major depressive disorder, bipolar disorder, and posttraumatic stress disorder.

Stress-related disorders, such as mood disorders and posttraumatic stress disorder (PTSD), are more common in women than in men. This sex difference is at least partly due to the organizing effect of sex steroids during intrauterine development, while activating or inhibiting effects of circulating sex hormones in the postnatal period and adulthood also play a role. Such effects result in structural and functional changes in neuronal networks, neurotransmitters, and neuropeptides, which make the arousal- and stress-related brain systems more vulnerable to environmental stressful events in women.

Sensory Glia Detect Repulsive Odorants and Drive Olfactory Adaptation.

Glia are typically considered as supporting cells for neural development and synaptic transmission. Here, we report an active role of a glia in olfactory transduction. As a polymodal sensory neuron in C.

Activation of astrocytes in hippocampus decreases fear memory through adenosine A receptors.

Astrocytes respond to and regulate neuronal activity, yet their role in mammalian behavior remains incompletely understood. Especially unclear is whether, and if so how, astrocyte activity regulates contextual fear memory, the dysregulation of which leads to pathological fear-related disorders. We generated rats to allow the specific activation of astrocytes in vivo by optogenetics.

Neural Regulation of Feeding Behavior.

Food intake and energy homeostasis determine survival of the organism and species. Information on total energy levels and metabolic state are sensed in the periphery and transmitted to the brain, where it is integrated and triggers the animal to forage, prey, and consume food. Investigating circuitry and cellular mechanisms coordinating energy balance and feeding behaviors has drawn on many state-of-the-art techniques, including gene manipulation, optogenetics, virus tracing, and single-cell sequencing.

Neurobiology and Neural Circuits of Aggression.

Aggression takes several forms and can be offensive or defensive. Aggression between animals of the same species or society aims to inflict harm upon another for the purpose of protecting a resource such as food, reproductive partners, territory, or status. This chapter explores the neurobiology of aggression.

Molecular Crux of Hair Cell Mechanotransduction Machinery.

Although 62 years have elapsed since the first report of hereditary deafness in a mouse strain, the molecular mechanism of hair cell mechanotransduction remains elusive. Three recent studies present crucial insights into the molecular crux of hair cell mechanotransduction machinery.

Structural basis of GPBAR activation and bile acid recognition.

The G-protein-coupled bile acid receptor (GPBAR) conveys the cross-membrane signalling of a vast variety of bile acids and is a signalling hub in the liver-bile acid-microbiota-metabolism axis. Here we report the cryo-electron microscopy structures of GPBAR-G complexes stabilized by either the high-affinity P395 or the semisynthesized bile acid derivative INT-777 at 3 Å resolution. These structures revealed a large oval pocket that contains several polar groups positioned to accommodate the amphipathic cholic core of bile acids, a fingerprint of key residues to recognize diverse bile acids in the orthosteric site, a putative second bile acid-binding site with allosteric properties and structural features that contribute to bias properties.

[Novel coronavirus infection (COVID-19) and nervous system involvement: pathogenesis, clinical manifestations, organization of neurological care].

Novel coronavirus SARS-CoV-2 and COVID-19, besides affecting the respiratory system, may lead to central and peripheral nervous system disorders and also cause muscular symptoms. The authors review the literature and own clinical case with respect to nervous system involvement in COVID-19 patients. There is a correlation between the severity of COVID-19 and the severity and frequency of neurologic complications.

Cryo-EM structures of inactive and active GABA receptor.

Metabotropic GABA G protein-coupled receptor functions as a mandatory heterodimer of GB1 and GB2 subunits and mediates inhibitory neurotransmission in the central nervous system. Each subunit is composed of the extracellular Venus flytrap (VFT) domain and transmembrane (TM) domain. Here we present cryo-EM structures of full-length human heterodimeric GABA receptor in the antagonist-bound inactive state and in the active state complexed with an agonist and a positive allosteric modulator in the presence of G protein at a resolution range of 2.

A Highly Sensitive Amperometric Glutamate Oxidase Microbiosensor Based on a Reduced Graphene Oxide/Prussian Blue Nanocube/Gold Nanoparticle Composite Film-Modified Pt Electrode.

A simple method that relies only on an electrochemical workstation has been investigated to fabricate a highly sensitive glutamate microbiosensor for potential neuroscience applications. In this study, in order to develop the highly sensitive glutamate electrode, a 100 µm platinum wire was modified by the electrochemical deposition of gold nanoparticles, Prussian blue nanocubes, and reduced graphene oxide sheets, which increased the electroactive surface area; and the chitosan layer, which provided a suitable environment to bond the glutamate oxidase. The optimization of the fabrication procedure and analytical conditions is described.

Circuits and functions of the lateral habenula in health and in disease.

The past decade has witnessed exponentially growing interest in the lateral habenula (LHb) owing to new discoveries relating to its critical role in regulating negatively motivated behaviour and its implication in major depression. The LHb, sometimes referred to as the brain's 'antireward centre', receives inputs from diverse limbic forebrain and basal ganglia structures, and targets essentially all midbrain neuromodulatory systems, including the noradrenergic, serotonergic and dopaminergic systems. Its unique anatomical position enables the LHb to act as a hub that integrates value-based, sensory and experience-dependent information to regulate various motivational, cognitive and motor processes.

Increased alcohol preference and intake in nicotine-preferring rats.

Background: Alcohol and tobacco are among the leading substances that are misused together and shared genetic vulnerability is likely. Increased susceptibility to nicotine self-administration has been shown in alcohol-preferring rat-lines. However, a nicotine-preferring (nP) rat-line has not been studied for alcohol preference.

The gist of Anne Treisman's revolution.

Anne Treisman investigated many aspects of perception, and in particular the roles of different forms of attention. Four aspects of her work are reviewed here, including visual search, set mean perception, perception in special populations, and binocular rivalry. The importance of the breakthrough in each case is demonstrated.

Safety, efficacy, and mechanisms of action of cannabinoids in neurological disorders.

In the past two decades, there has been an increasing interest in the therapeutic potential of cannabinoids for neurological disorders such as epilepsy, multiple sclerosis, pain, and neurodegenerative diseases. Cannabis-based treatments for pain and spasticity in patients with multiple sclerosis have been approved in some countries. Randomised controlled trials of plant-derived cannabidiol for treatment of Lennox-Gastaut syndrome and Dravet syndrome, two severe childhood-onset epilepsies, provide evidence of anti-seizure effects.

Inflammation, Iron, Energy Failure, and Oxidative Stress in the Pathogenesis of Multiple Sclerosis.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Different trigger pathologies have been suggested by the primary cytodegenerative "inside-out" and primary inflammation-driven "outside-in" hypotheses. Recent data indicate that mitochondrial injury and subsequent energy failure are key factors in the induction of demyelination and neurodegeneration.

An fMRI study dissociating distance measures computed by Broca's area in movement processing: clause boundary vs. identity.

Behavioral studies of sentence comprehension suggest that processing long-distance dependencies is subject to interference effects when Noun Phrases (NP) similar to the dependency head intervene in the dependency. Neuroimaging studies converge in localizing such effects to Broca's area, showing that activity in Broca's area increases with the number of NP interveners crossed by a moved NP of the same type. To test if NP interference effects are modulated by adding an intervening clause boundary, which should by hypothesis increase the number of successive-cyclic movements, we conducted an fMRI study contrasting NP interveners with clausal (CP) interveners.

Bitter taste and nicotine preference: evidence for sex differences in rats.

Background: Nicotine affects sensory pathways and an interaction between taste and nicotine preference is likely. In addition to pharmacologic effects, orosensory factors are important in nicotine dependence. Recent evidence suggests a link between taste (notably bitter) receptor genes and nicotine addiction.

Neuromuscular synapse integrity requires linkage of acetylcholine receptors to postsynaptic intermediate filament networks via rapsyn-plectin 1f complexes.

Mutations in the cytolinker protein plectin lead to grossly distorted morphology of neuromuscular junctions (NMJs) in patients suffering from epidermolysis bullosa simplex (EBS)-muscular dystrophy (MS) with myasthenic syndrome (MyS). Here we investigated whether plectin contributes to the structural integrity of NMJs by linking them to the postsynaptic intermediate filament (IF) network. Live imaging of acetylcholine receptors (AChRs) in cultured myotubes differentiated ex vivo from immortalized plectin-deficient myoblasts revealed them to be highly mobile and unable to coalesce into stable clusters, in contrast to wild-type cells.

Tamoxifen and mifepriston modulate nicotine induced conditioned place preference in female rats.

An increasing number of studies suggest that nicotine/tobacco addiction is modulated by ovarian hormones. The levels of estrogen and progesterone appear to be important in the success of quit attempts and smoking cessation. In women smokers with the diagnosis or risk of breast cancer, the estrogen receptor modulator tamoxifen (TAM) is widely used, and even though the detrimental health effects of smoking are known, this vulnerable group has difficulty quitting and continues to smoke.

Effects of nitric oxide synthase inhibition on spatial discrimination learning and central DA2 and mACh receptors.

Cholinergic and dopaminergic systems are involved in spatial memory and are modulated by nitric oxide (NO); NO has well documented effects on place learning in rodents. The aim of the present study was to investigate the effect of NOS inhibition on place learning in the water maze and to evaluate the relationships between NOS inhibition, learning performance, dopamine (DA) D2 and muscarinic acetylcholine (mACh) receptors. Male Sprague-Dawley rats received the NOS inhibitor Nomega-Nitro-l-Arginine (l-NA), or saline and were trained in the water maze.

Relationship of lumen diameter to type and degree of arterial remodeling at sites of expanding wall or plaque thickness in human carotid artery.

Background: Arterial remodeling exhibits a bidirectional capacity. Whether lumen size affects remodeling response to lesion change is unknown.

Methods: Prospective study by duplex ultrasonography over 2 years in 61 subjects with coronary artery disease.

Effect of carbon monoxide on dopamine and glutamate uptake and cGMP levels in rat brain.

After the recognition of nitric oxide (NO) as a messenger molecule in the nervous system, carbon monoxide (CO) has received attention with similar properties. The present study aims to elucidate the effects of CO on synaptosomal dopamine ((3)H-DA) and glutamate ((3)H-Glu) uptake and on cGMP levels; possible interaction between NO and CO systems was also evaluated. Our results provide evidence for the inhibition of DA and Glu uptake by CO in a time-, dose-, and temperature-dependent manner in rat striatum and hippocampus, respectively; the inhibition observed was sexually dimorphic with more pronounced effects in females.

The effect of octreotide on kainate-induced wet dog shakes and seizure activity in male and female rats.

Systemic kainic acid (KA) administration to rats triggers wet dog shakes (WDS) followed by epileptic seizures. Although WDS are often associated with the occurrence of seizures, we have recently shown that following nitric oxide (NO) synthesis inhibition, the number of WDS decreased; subsequently the onset of seizure activity was shortened, and the number of convulsions was increased. Somatostatin (SS), whose release appears to be controlled by NO, inhibits seizure activity.