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Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF) synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

Asymmetric tidal turbulence (ATT) strongly influences estuarine health and functioning. However, its impact on the three-dimensional estuarine dynamics and the feedback of water motion and salinity distribution on ATT remain poorly understood, especially for short estuaries (estuarine length « tidal wavelength). This study systematically investigates the abovementioned interactions in a short estuary for the first time, considering periodically weakly stratified conditions. This is done by developing a three-dimensional semi-analytical model (combining perturbation method with finite element method) that allows a dissection of the contributions of different processes to ATT, estuarine circulation, and salt transport. The generation of ATT is dominated by (i) strain-induced periodic stratification and (ii) asymmetric bottom-shear-generated turbulence, and their contributions to ATT are different both in amplitude and phase. The magnitude of the residual circulation related to ATT and the eddy viscosity--shear covariance (ESCO) is about half of that of the gravitational circulation (GC) and shows a ''reversed'' pattern as compared to GC. ATT generated by strain-induced periodic stratification contributes to an ESCO circulation with a spatial structure similar to GC. This circulation reduces the longitudinal salinity gradients and thus weakens GC. Contrastingly, the ESCO circulation due to asymmetric bottom-shear-generated turbulence shows patterns opposite to GC and acts to enhance GC. Concerning the salinity dynamics at steady state, GC and tidal pumping are equally important to salt import, whereas ESCO circulation yields a significant seaward salt transport. These findings highlight the importance of identifying the sources of ATT to understand its impact on estuarine circulation and salt distribution. [ABSTRACT FROM AUTHOR]

The holotype specimen of the Late Triassic dinosauriform Caseosaurus crosbyensis is redescribed and evaluated phylogenetically for the first time, providing new anatomical information and data on the earliest dinosaurs and their evolution within the dinosauromorph lineage. Historically, Caseosaurus crosbyensis has been considered to represent an early saurischian dinosaur, and often a herrerasaur. More recent work on Triassic dinosaurs has cast doubt over its supposed dinosaurian affinities and uncertainty about particular features in the holotype and only known specimen has led to the species being regarded as a dinosauriform of indeterminate position. Here, we present a new diagnosis for Caseosaurus crosbyensis and refer additional material to the taxon--a partial right ilium from Snyder Quarry. Our comparisons and phylogenetic analyses suggest that Caseosaurus crosbyensis belongs in a clade with herrerasaurs and that this clade is the sister taxon of Dinosauria, rather than positioned within it. This result, along with other recent analyses of early dinosaurs, pulls apart what remains of the "traditional" group of dinosaurs collectively termed saurischians into a polyphyletic assemblage and implies that Dinosauria should be regarded as composed exclusively of Ornithoscelida (Ornithischia + Theropoda) and Sauropodomorpha. In addition, our analysis recovers the enigmatic European taxon Saltopus elginensis among herrerasaurs for the first time. This result suggests a greater body-size range for herrerasaurs than previously thought and provides further evidence for their presence in Europe during the Late Triassic. If this hypothesis is correct then this clade of herrerasaurs also represents the first clade of non-dinosaurian dinosauromorphs known to contain large-bodied carnivorous species. The results of our analyses also highlight the distinction between the clades Herrerasauridae and Herrerasauria, as they are currently defined, and necessitate a provisional revival of the latter until future works can better resolve the relationships among these important early taxa. [ABSTRACT FROM AUTHOR]

Investigating the roles of synaptogenic adhesion molecules during synapse formation has proven challenging, often due to compensatory functions between additional family members. The synaptic cell adhesion molecules 1-3 (SynCAM1-3) are expressed both pre- and postsynaptically, share highly homologous domains and are synaptogenic when ectopically presented to neurons; yet their endogenous functions during synaptogenesis are unclear. Here we report that SynCAM1-3 are functionally redundant and collectively necessary for synapse formation in cultured hippocampal neurons. Only triple knockdown (KD) of SynCAM1-3 using highly efficient, chained artificial microRNAs (amiRNAs) reduced synapse density and increased synapse area. Electrophysiological recordings of quantal release events supported an increase in synapse size caused by SynCAM1-3 depletion. Furthermore, a combinatorial, mosaic lentiviral approach comparing wild type (WT) and SynCAM1-3 KD neurons in the same culture demonstrate that SynCAM1-3 set synapse number and size through postsynaptic mechanisms. The results demonstrate that the redundancy between SynCAM1-3 has concealed their synaptogenic function at the postsynaptic terminal. [ABSTRACT FROM AUTHOR]

Synaptic target specificity, whereby neurons make distinct types of synapses with different target cells, is critical for brain function, yet the mechanisms driving it are poorly understood. In this study, we demonstrate Kirrel3 regulates target-specific synapse formation at hippocampal mossy fiber (MF) synapses, which connect dentate granule (DG) neurons to both CA3 and GABAergic neurons. Here, we show Kirrel3 is required for formation of MF filopodia; the structures that give rise to DG-GABA synapses and that regulate feed-forward inhibition of CA3 neurons. Consequently, loss of Kirrel3 robustly increases CA3 neuron activity in developing mice. Alterations in the Kirrel3 gene are repeatedly associated with intellectual disabilities, but the role of Kirrel3 at synapses remained largely unknown. Our findings demonstrate that subtle synaptic changes during development impact circuit function and provide the first insight toward understanding the cellular basis of Kirrel3-dependent neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]