We revise cosmological mass bounds on hadronic axions in low-reheating cosmological scenarios, with a reheating temperature \(T_{\rm RH}~\le 100\) MeV, in light of the latest cosmological ...observations. In this situation, the neutrino decoupling would be unaffected, while the thermal axion relic abundance is suppressed. Moreover, axions are colder in low-reheating temperature scenarios, so that bounds on their abundance are possibly loosened. As a consequence of these two facts, cosmological mass limits on axions are relaxed. Using state-of-the-art cosmological data and characterizing axion-pion interactions at the leading order in chiral perturbation theory, we find in the standard case an axion mass bound \(m_a < 0.26\) eV. However, axions with masses \(m_a \simeq 1\) eV, or heavier, would be allowed for reheating temperatures \(T_{\rm RH} \lesssim 80\) MeV. Multi-eV axions would be outside the mass sensitivity of current and planned solar axion helioscopes and would demand new experimental approaches to be detected.
We present a novel formalism to describe the \(in\) \(vacuo\) conversion between polarization states of propagating radiation, also known as generalized Faraday effect (GFE), in a cosmological ...context. Thinking of GFE as a potential tracer of new, isotropy- and/or parity-violating physics, we apply our formalism to the cosmic microwave background (CMB) polarized anisotropy power spectra, providing a simple framework to easily compute their observed modifications. In so doing, we re-interpret previously known results, namely the \(in\) \(vacuo\) rotation of the linear polarization plane of CMB photons (or cosmic birefringence) but also point out that GFE could lead to the partial conversion of linear into circular polarization. We notice that GFE can be seen as an effect of light propagating in an anisotropic and/or chiral medium (a "dark crystal") and recast its parameters as the components of an effective "cosmic susceptibility tensor". For a wave number-independent susceptibility tensor, this allows us to set an observational bound on a GFE-induced CMB circularly polarized power spectrum, or \(VV\), at \(C_{\ell}^{VV} < 2 \times 10^{-5} \mu K^2\) (95 \% C.L.), at its peak \(\ell\simeq 370\), which is some 3 orders of magnitude better than presently available direct \(VV\) measurements. We argue that, unless dramatic technological improvements will arise in direct \(V\)-modes measurements, cosmic variance-limited linear polarization surveys expected within this decade should provide, as a byproduct, superior bounds on GFE-induced circular polarization of the CMB.
Secret contact interactions among eV sterile neutrinos, mediated by a massive gauge boson \(X\) (with \(M_X \ll M_W\)), and characterized by a gauge coupling \(g_X\), have been proposed as a mean to ...reconcile cosmological observations and short-baseline laboratory anomalies. We constrain this scenario using the latest Planck data on Cosmic Microwave Background anisotropies, and measurements of baryon acoustic oscillations (BAO). We consistently include the effect of secret interactions on cosmological perturbations, namely the increased density and pressure fluctuations in the neutrino fluid, and still find a severe tension between the secret interaction framework and cosmology. In fact, taking into account neutrino scattering via secret interactions, we derive our own mass bound on sterile neutrinos and find (at 95% CL) \(m_s < 0.82\) eV or \(m_s < 0.29\) eV from Planck alone or in combination with BAO, respectively. These limits confirm the discrepancy with the laboratory anomalies. Moreover, we constrain, in the limit of contact interaction, the effective strength \(G_X\) to be \( < 2.8 (2.0) \times 10^{10}\,G_F\) from Planck (Planck+BAO). This result, together with the mass bound, strongly disfavours the region with \(M_X \sim 0.1\) MeV and relatively large coupling \(g_X\sim 10^{-1}\), previously indicated as a possible solution to the small scale dark matter problem.
(Abridged) Neutrino interactions beyond the standard model may affect the cosmological evolution and can be constrained through observations. We consider the possibility that neutrinos possess secret ...scalar or pseudoscalar interactions mediated by the Nambu-Goldstone boson of a still unknown spontaneously broken global \(U(1)\) symmetry, as in, e.g. , Majoron models. In such scenarios, neutrinos still decouple at \(T\simeq 1\) MeV, but become tightly coupled again ('recouple') at later stages of the cosmological evolution. We use available observations of CMB anisotropies, including Planck 2013 and the joint BICEP2/Planck 2015 data, to derive constraints on the quantity \(\gamma_{\nu \nu}^4\), parameterizing the neutrino collision rate due to (pseudo)scalar interactions. We consider both a minimal extension of the standard \(\Lambda\)CDM model, and scenarios with extra relativistic species or non-vanishing tensors. We find a typical constraint \(\gamma_{\nu \nu}^4 < 0.9\times 10^{-27}\) (95% C.L.), implying an upper limit on the redshift \(z_{rec}\) of neutrino recoupling \(< 8500\). In the framework of Majoron models, the upper limit on \(\gamma_{\nu \nu}\) roughly translates on a constraint \(g < 8.2\times 10^{-7}\) on the Majoron-neutrino coupling constant \(g\). In general, the data show a weak (\(\sim 1\sigma\)) but intriguing preference for non-zero values of \(\gamma_{\nu \nu}^4\), with best fits in the range \(\gamma_{\nu \nu}^4 = (0.15 - 0.35)\times 10^{-27}\), depending on the particular dataset. This is more evident when either observations from ACT and SPT are included, or the possibility of non-vanishing tensor modes is considered. In particular, for the minimal model \(\Lambda\)CDM +\(\gamma_{\nu \nu}\) and including the Planck 2013, ACT and SPT data, we report \(\gamma_{\nu \nu}^4=( 0.45^{+0.15}_{-0.38} )\times10^{-27}\) (\(200 < z_{rec} < 5700\)) at 68% confidence level.
Lensing of the CMB is now a well-developed probe of large-scale clustering over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE ...mission can produce a clean map of the lensing deflections over nearly the full-sky. The number of high-S/N modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that it will enable. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous BAO measurements, three times smaller than the minimum total mass allowed by neutrino oscillations. In the search for B-mode polarization from primordial gravitational waves with CORE, lens-induced B-modes will dominate over instrument noise, limiting constraints on the gravitational wave power spectrum amplitude. With lensing reconstructed by CORE, one can "delens" the observed polarization internally, reducing the lensing B-mode power by 60%. This improves to 70% by combining lensing and CIB measurements from CORE, reducing the error on the gravitational wave amplitude by 2.5 compared to no delensing (in the null hypothesis). Lensing measurements from CORE will allow calibration of the halo masses of the 40000 galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. CORE can accurately remove Galactic emission from CMB maps with its 19 frequency channels. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE. abridged
We forecast the main cosmological parameter constraints achievable with the CORE space mission which is dedicated to mapping the polarisation of the Cosmic Microwave Background (CMB). CORE was ...recently submitted in response to ESA's fifth call for medium-sized mission proposals (M5). Here we report the results from our pre-submission study of the impact of various instrumental options, in particular the telescope size and sensitivity level, and review the great, transformative potential of the mission as proposed. Specifically, we assess the impact on a broad range of fundamental parameters of our Universe as a function of the expected CMB characteristics, with other papers in the series focusing on controlling astrophysical and instrumental residual systematics. In this paper, we assume that only a few central CORE frequency channels are usable for our purpose, all others being devoted to the cleaning of astrophysical contaminants. On the theoretical side, we assume LCDM as our general framework and quantify the improvement provided by CORE over the current constraints from the Planck 2015 release. We also study the joint sensitivity of CORE and of future Baryon Acoustic Oscillation and Large Scale Structure experiments like DESI and Euclid. Specific constraints on the physics of inflation are presented in another paper of the series. In addition to the six parameters of the base LCDM, which describe the matter content of a spatially flat universe with adiabatic and scalar primordial fluctuations from inflation, we derive the precision achievable on parameters like those describing curvature, neutrino physics, extra light relics, primordial helium abundance, dark matter annihilation, recombination physics, variation of fundamental constants, dark energy, modified gravity, reionization and cosmic birefringence. (ABRIDGED)
Acute environmental stress rarely implies long‐lasting neurophysiological and behavioral alterations. On the contrary, chronic stress exerts a potent toxic effect at the glutamatergic synapse whose ...altered physiology has been recognized as a core trait of neuropsychiatric disorders. The endocannabinoid system (ECS) plays an important role in the homeostatic response to acute stress. In particular, stress induces synthesis of endocannabinoid (eCB) 2‐arachidonyl glycerol (2‐AG). 2‐AG stimulates presynaptic cannabinoid 1 (CB1) receptor contributing to stress response termination through inhibition of glutamate release, restraining thereafter anxiety arousal. We employ mouse models of stress response coupled to gene expression analyses, unravelling that in response to acute psychosocial stress in the mouse hippocampus, ECS‐mediated synaptic modulation is enhanced via transcriptional repression of two enzymes involved in 2‐AG degradation: α/β‐hydrolase domain containing 6 (ABHD6) and monoacylglycerol lipase (MAGL). Such a process is orchestrated by the epigenetic corepressor LSD1 who directly interacts with promoter regulatory regions of Abhd6 and Magl. Remarkably, negative transcriptional control of Abhd6 and Magl is lost in the hippocampus upon chronic psychosocial stress, possibly contributing to trauma‐induced drift of synapse physiology toward uncontrolled glutamate transmission. We previously showed that in mice lysine‐specific demethylase 1 (LSD1) increases its hippocampal expression in response to psychosocial stress preventing excessive consolidation of anxiety‐related plasticity. In this work, we unravel a nodal epigenetic modulation of eCB turn over, shedding new light on the molecular substrate of converging stress‐terminating effects displayed by ECS and LSD1.
Environmental stress engages physiological responses primed by synaptic activation. In the nucleus direct psychosocial stress effects induce a program of neuroplasticity‐related gene expression instrumental to memory consolidation of the negative experience. On the behavioral point of view, stress response directly elicits anxiety arousal and increased vigilance. A slower homeostatic response to stress entails nuclear, synaptic, and behavioral adaptations instrumental to stress response termination. We show that direct targets of LSD1 transcriptional repression at the nuclear level are 2‐AG degrading enzymes ABHD6 and MAGL. In response to stress their expression is reduced helping to maintain active 2‐AG concentrations via LSD1‐mediated mechanism.
Ten to 20% of western countries population suffers from major depression disorder (MDD). Stressful life events represent the main environmental risk factor contributing to the onset of MDD and other ...stress-related neuropsychiatric disorders. In this regard, investigating brain physiology of stress response underlying the remarkable individual variability in terms of behavioral outcome may uncover stress-vulnerability pathways as a source of candidate targets for conceptually new antidepressant treatments. Serum response factor (SRF) has been addressed as a stress transducer via promoting inherent experience-induced
Immediate Early Genes
(
IEGs
) expression in neurons. However, in resting conditions, SRF also represents a transcriptional repressor able to assemble the core LSD1/CoREST/HDAC2 corepressor complex, including demethylase and deacetylase activities. We here show that dominant negative SRF splicing isoform lacking most part of the transactivation domain, namely SRFΔ5, owes its transcriptional repressive behavior to the ability of assembling LSD1/CoREST/HDAC2 corepressor complex meanwhile losing its affinity for transcription-permissive cofactor ELK1. SRFΔ5 is highly expressed in the brain and developmentally regulated. In the light of its activity as negative modulator of dendritic spine density, SRFΔ5 increase along with brain maturation suggests a role in synaptic pruning. Upon acute psychosocial stress, SRFΔ5 isoform transiently increases its levels. Remarkably, when stress is chronically repeated, a different picture occurs where SRF protein becomes stably upregulated in vulnerable mice but not in resilient animals. These data suggest a role for SRFΔ5 that is restricted to acute stress response, while positive modulation of SRF during chronic stress matches the criteria for stress-vulnerability hallmark.
The study of neurons is fundamental to unraveling the complexities of the nervous system. Primary neuronal cultures from rodents have long been a cornerstone of experimental studies, yet limitations ...related to their non-human nature and ethical concerns have prompted the development of alternatives. In recent years, the derivation of neurons from human-induced pluripotent stem cells (hiPSCs) has emerged as a powerful option, offering a scalable source of cells for diverse applications. Neural progenitor cells (NPCs) derived from hiPSCs can be efficiently differentiated into functional neurons, providing a platform to study human neural physiology and pathology in vitro. However, challenges persist in achieving consistent and reproducible outcomes across experimental settings.
Our aim is to provide a step-by-step methodological protocol, augmenting existing procedures with additional instructions and parameters, to guide researchers in achieving reproducible results.
We outline procedures for the differentiation of hiPSC-derived NPCs into electrically competent neurons, encompassing initial cell density, morphology, maintenance, and differentiation. We also describe the analysis of specific markers for assessing neuronal phenotype, along with electrophysiological analysis to evaluate biophysical properties of neuronal excitability. Additionally, we conduct a comparative analysis of three different chemical methods—KCl, N-methyl-D-aspartate (NMDA), and bicuculline—to induce neuronal depolarization and assess their effects on the induction of both fast and slow post-translational, transcriptional, and post-transcriptional responses.
Our protocol provides clear instructions for generating reliable human neuronal cultures with defined electrophysiological properties to investigate neuronal differentiation and model diseases in vitro.
•A protocol to obtain excitable neurons from human iPSCs.•Key parameters are highlighted to follow neuronal differentiation.•Cultures obtained present 75 % of NeuN+ neurons.•KCl mediated depolarization provides consistent fast and slow molecular responses.
Recent branching (100 MYA) of the mammalian evolutionary tree has enhanced brain complexity and functions at the putative cost of increased emotional circuitry vulnerability. Thus, to better ...understand psychopathology, a burden for the modern society, novel approaches should exploit evolutionary aspects of psychiatric-relevant molecular pathways. A handful of genes is nowadays tightly associated to psychiatric disorders. Among them, neuronal-enriched RbFOX1 modifies the activity of synaptic regulators in response to neuronal activity, keeping excitability within healthy domains. We here dissect a higher primates-restricted interaction between RbFOX1 and the transcriptional corepressor Lysine Specific Demethylase 1 (LSD1/KDM1A). A single nucleotide variation (AA to AG) in
gene appeared in higher primates and humans, endowing RbFOX1 with the ability to promote the alternative usage of a novel 3' AG splice site, which extends LSD1 exon E9 in the upstream intron (E9-long). Exon E9-long regulates LSD1 levels by Nonsense-Mediated mRNA Decay. As reintroduction of the archaic
variant (AA) abolishes E9-long splicing, the novel 3' AG splice site is necessary for RbFOX1 to control LSD1 levels. LSD1 is a homeostatic immediate early genes (IEGs) regulator playing a relevant part in environmental stress-response. In primates and humans, inclusion of LSD1 as RbFOX1 target provides RbFOX1 with the additional ability to regulate the IEGs. These data, together with extensive RbFOX1 involvement in psychiatric disorders and its stress-dependent regulation in male mice, suggest the RbFOX1-LSD1-IEGs axis as an evolutionary recent psychiatric-relevant pathway. Notably, outside the nervous system, RbFOX2-dependent LSD1 modulation could be a candidate deregulated mechanism in cancer.
To be better understood, anxiety and depression need large human genetics studies aimed at further resolving the often ambiguous, aberrant neuronal pathomechanisms that impact corticolimbic circuitry physiology. Several genetic associations of the alternative splicing regulator RbFOX1 with psychiatric conditions suggest homeostatic unbalance as a neuronal signature of psychopathology. Here we move a step forward, characterizing a disease-relevant higher primates-specific pathway by which RbFOX1 acquires the ability to regulate neuronal levels of Lysine Specific Demethylase 1, an epigenetic modulator of environmental stress response. Thus, two brain-enriched enzymes, independently shown to homeostatically protect neurons with a clear readout in terms of emotional behavior in lower mammals, establish in higher primates and humans a new functional cooperation enhancing the complexity of environmental adaptation and stress vulnerability.
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