Neuromodulated plasticity of the connectivity between the Prefrontal Cortex and the noradrenergic Locus Coeruleus

Incentive stimuli and environmental stressors are encoded at the level of the prefrontal cortex (PFC) circuits, which send their glutamatergic excitatory projections to several neuromodulatory regions, including the Locus Coeruleus (LC), the major source of noradrenaline (NA) for the entire forebrain. Despite the potential implications for NA-mediated regulation of action control and for the etiology of stress-related neuropsychiatric conditions, it remains to be established how LC neuronal activity is shaped by impinging PFC inputs (PFC\uf0e0LC) to affect behavior, and whether these inputs are modulated by in-vivo experience. By combining neurophysiological and optogenetic approaches together with behavioral paradigms in mice, we found that PFC \uf0e0LC stimulation supports learning and retrieval of contextual memory associations. Consistent with the occurrence of plasticity processes at LC synapses, long-lasting modulation of PFC\uf0e0LC projections relies on the endocannabinoid (eCB)-mediated signaling capacity, which is dynamically shaped by context adaptations and stress salience experiences. We also found that eCB-plasticity at PFC \u2192 LC synapses is regulated during the adolescence to adulthood transition. In summary, our results not only dissect the behavioral implications of neuromodulated plasticity at PFC inputs to the LC, but also unveil divergent synaptic substrates during postnatal development, which might be relevant to explain some of the different noradrenergic-mediated response in adolescents and adults. \u200

Trust, but verify. De-anchoring of inflation expectations under learning and heterogeneity

The paper studies how a prolonged period of subdued price developments may induce a de-anchoring of inflation expectations from the central bank's objective. This is shown within a framework where agents form expectations using adaptive learning, choosing among a set of alternative forecasting models. The analysis is accompanied by empirical evidence on the properties of inflation expectations in the euro area. Our results also suggest that monetary policy may lose effectiveness if delayed too much, as expectations are allowed to drift away from target for too long

Basel III: Long-term impact on economic performance and fluctuations

We assess the long-term economic impact of the new regulatory standards (the Basel III reform), answering the following questions. (1) What is the impact of the reform on long-term economic performance? (2) What is the impact of the reform on economic fluctuations? (3) What is the impact of the adoption of countercyclical capital buffers on economic fluctuations? The main results are the following. (1) Each percentage point increase in the capital ratio causes a median 0.09 percent decline in the level of steady state output, relative to the baseline. The impact of the new liquidity regulation is of a similar order of magnitude, at 0.08 percent. This paper does not estimate the benefits of the new regulation in terms of reduced frequency and severity of financial crisis, analysed in Basel Committee on Banking Supervision (BCBS, 2010b). (2) The reform should dampen output volatility; the magnitude of the effect is heterogeneous across models; the median effect is modest. (3) The adoption of countercyclical capital buffers could have a more sizeable dampening effect on output volatility. These conclusions are fully consistent with those of reports by the Long-term Economic Impact group (BCBS, 2010b) and Macro Assessment Group (MAG, 2010b).Basel III, countercyclical capital buffers, financial (in)stability, procyclicality, macroprudential

mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity.

Postmortem studies have revealed increased density of excitatory synapses in the brains of individuals with autism spectrum disorder (ASD), with a putative link to aberrant mTOR-dependent synaptic pruning. ASD is also characterized by atypical macroscale functional connectivity as measured with resting-state fMRI (rsfMRI). These observations raise the question of whether excess of synapses causes aberrant functional connectivity in ASD. Using rsfMRI, electrophysiology and in silico modelling in Tsc2 haploinsufficient mice, we show that mTOR-dependent increased spine density is associated with ASD -like stereotypies and cortico-striatal hyperconnectivity. These deficits are completely rescued by pharmacological inhibition of mTOR. Notably, we further demonstrate that children with idiopathic ASD exhibit analogous cortical-striatal hyperconnectivity, and document that this connectivity fingerprint is enriched for ASD-dysregulated genes interacting with mTOR or Tsc2. Finally, we show that the identified transcriptomic signature is predominantly expressed in a subset of children with autism, thereby defining a segregable autism subtype. Our findings causally link mTOR-related synaptic pathology to large-scale network aberrations, revealing a unifying multi-scale framework that mechanistically reconciles developmental synaptopathy and functional hyperconnectivity in autism

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe