The present and future status of heavy neutral leptons

The existence of nonzero neutrino masses points to the likely existence of multiple Standard Model neutral fermions. When such states are heavy enough that they cannot be produced in oscillations, they are referred to as heavy neutral leptons (HNLs). In this white paper, we discuss the present experimental status of HNLs including colliders, beta decay, accelerators, as well as astrophysical and cosmological impacts. We discuss the importance of continuing to search for HNLs, and its potential impact on our understanding of key fundamental questions, and additionally we outline the future prospects for next-generation future experiments or upcoming accelerator run scenarios

EuCAPT White Paper: Opportunities and Challenges for Theoretical Astroparticle Physics in the Next Decade

Astroparticle physics is undergoing a profound transformation, due to a series of extraordinary new results, such as the discovery of high-energy cosmic neutrinos with IceCube, the direct detection of gravitational waves with LIGO and Virgo, and many others. This white paper is the result of a collaborative effort that involved hundreds of theoretical astroparticle physicists and cosmologists, under the coordination of the European Consortium for Astroparticle Theory (EuCAPT). Addressed to the whole astroparticle physics community, it explores upcoming theoretical opportunities and challenges for our field of research, with particular emphasis on the possible synergies among different subfields, and the prospects for solving the most fundamental open questions with multi-messenger observations.Comment: White paper of the European Consortium for Astroparticle Theory (EuCAPT). 135 authors, 400 endorsers, 133 pages, 1382 reference

The present and future status of heavy neutral leptons

The existence of nonzero neutrino masses points to the likely existence of multiple Standard Model neutral fermions. When such states are heavy enough that they cannot be produced in oscillations, they are referred to as heavy neutral leptons (HNLs). In this white paper, we discuss the present experimental status of HNLs including colliders, beta decay, accelerators, as well as astrophysical and cosmological impacts. We discuss the importance of continuing to search for HNLs, and its potential impact on our understanding of key fundamental questions, and additionally we outline the future prospects for next-generation future experiments or upcoming accelerator run scenarios.Peer reviewe

Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances

New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and transporter-mediated release of NE and DA, thus showing a more catecholamine-selective profile. MDMA-like NPS frequently induce well-being, empathy, and prosocial effects and have only moderate psychostimulant properties. These MDMA-like substances primarily act by inhibiting the serotonin (5-HT) transporter (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically, amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of this chapter is to review the state of knowledge regarding these substances with a focus on the description of the in vitro pharmacology of selected amphetamine- and MDMA-like NPS. In addition, it is aimed to provide links between pharmacological profiles and in vivo effects and toxicity, which leads to the conclusion that abuse liability for amphetamine-like NPS may be higher than for MDMA-like NPS, but that the risk for developing the life-threatening serotonin syndrome may be increased for MDMA-like NPS

Rôles des récepteurs du glutamate et de la dopamine dans l activation de l Extracellular-signal Regulated Kinase (ERK) par les psychostimulants dans le striatum

Les drogues d abus augmentent de la concentration extracellulaire de dopamine et induisent la phosphorylation de l Extracellular-signal Regulated Kinase (ERK) dans le striatum. L activation de ERK par la cocaïne est dépendante de la stimulation des D1R et des récepteurs glutamatergiques NMDA (NMDAR) et joue un rôle clé dans les effets comportementaux à long terme. La voie de transduction du signal D1R/AMPc/PKA est importante pour l activation de ERK, par un mécanisme impliquant la DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32,000). De plus, l activation de ERK par la cocaïne, résulte d une potentialisation de la fonction des NMDAR, déclenchée par les D1R. Cette potentialisation dépend de la phosphorylation sur tyrosine de la sous-unité NR2B des NMDAR, via l activation de kinases de la famille de Src (SFKs). Ainsi, l influx calcique dépendant de la cascade D1R/SFKs/N2RB déclenche l activation de ERK en réponse à la cocaïne. D autre part, la voie D1R/AMPc/PKA/DARPP-32 révèle cet évènement, en inhibant des phosphatases de la voie ERKPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Addiction therapy. Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology

Circuit remodeling driven by pathological forms of synaptic plasticity underlies several psychiatric diseases, including addiction. Deep brain stimulation (DBS) has been applied to treat a number of neurological and psychiatric conditions, although its effects are transient and mediated by largely unknown mechanisms. Recently, optogenetic protocols that restore normal transmission at identified synapses in mice have provided proof of the idea that cocaine-adaptive behavior can be reversed in vivo. The most efficient protocol relies on the activation of metabotropic glutamate receptors, mGluRs, which depotentiates excitatory synaptic inputs onto dopamine D1 receptor medium-sized spiny neurons and normalizes drug-adaptive behavior. We discovered that acute low-frequency DBS, refined by selective blockade of dopamine D1 receptors, mimics optogenetic mGluR-dependent normalization of synaptic transmission. Consequently, there was a long-lasting abolishment of behavioral sensitization