Carbon-mixed dental cement for fixing fiber optic ferrules prevents visually triggered locomotive enhancement in mice upon optogenetic stimulation

Optogenetics enables activation/silencing of specific neurons with unprecedented temporal and spatial resolution. The method, however, is prone to artefacts associated with biophysics of light used for illuminating opsin-expressing neurons. Here we employed Tph2-mhChR2-YFP transgenic mice, which express channelrhodopsin (ChR2) only in serotonergic neurons in the brain, to investigate behavioral effects of optogenetic stimulation of serotonergic neurons. Surprisingly, optogenetic stimulation enhanced locomotion even in ChR2-negative mice. Such unspecific effects are likely to be due to visual agitation caused by light leakage from the dental cement, which is commonly used to fixate optic fiber ferrules on the skull. When we employed black dental cement made by mixing carbons with dental cement powders, such unspecific effects were abolished in ChR2-negative mice, but not in ChR2-positive mice, confirming that enhanced locomotion resulted from serotonergic activation. The method allows extracting genuine behavioral effects of optogenetic stimulation without contamination from visual stimuli caused by light leakage

Extension and stress during continental breakup: seismic anisotropy of the crust in Northern Afar

Studies that attempt to simulate continental rifting and subsequent breakup require detailed knowledge of crustal stresses, however observational constraints from continental rifts are lacking. In addition, a knowledge of the stress field around active volcanoes can be used to detect sub-surface changes to the volcanic system. Here we use shear wave splitting to measure the seismic anisotropy of the crust in Northern Afar, a region of active, magma-rich continental breakup. We combine shear wave splitting tomography with modelling of gravitational and magmatic induced stresses to propose a model for crustal stress and strain across the rift. Results show that at the Ethiopian Plateau, seismic anisotropy is consistently oriented N–S. Seismic anisotropy within the rift is generally oriented NNW–SSE, with the exception of regions north and south of the Danakil Depression where seismic anisotropy is rift-perpendicular. These results suggest that the crust at the rift axis is characterized by rift-aligned structures and melt inclusions, consistent with a focusing of tectonic extension at the rift axis. In contrast, we show that at regions within the rift where extension rate is minimal the seismic anisotropy is best explained by the gravitationally induced stress field originating from variations in crustal thickness. Seismic anisotropy away from the rift is controlled by a combination of inherited crustal structures and gravitationally induced extension whereas at the Dabbahu region we show that the stress field changes orientation in response to magmatic intrusions. Our proposed model provides a benchmark of crustal stress in Northern Afar which will aid the monitoring of volcanic hazard. In addition we show that gravitational forces play a key role in measurements of seismic anisotropy, and must be considered in future studies. We demonstrate that during the final stages of continental rifting the stress field at the rift axis is primarily controlled by tectonic extension, but that gravitational forces and magmatic intrusions can play a key role in the orientation of the stress field

Impacts of Brain Serotonin Deficiency following Tph2 Inactivation on Development and Raphe Neuron Serotonergic Specification

Brain serotonin (5-HT) is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2). Tph2 inactivation (Tph2-/-) resulted in brain 5-HT deficiency leading to growth retardation and persistent leanness, whereas a sex- and age-dependent increase in body weight was observed in Tph2+/- mice. The conserved expression pattern of the 5-HT neuron-specific markers (except Tph2 and 5-HT) demonstrates that brain 5-HT synthesis is not a prerequisite for the proliferation, differentiation and survival of raphe neurons subjected to the developmental program of serotonergic specification. Furthermore, although these neurons are unable to synthesize 5-HT from the precursor tryptophan, they still display electrophysiological properties characteristic of 5-HT neurons. Moreover, 5-HT deficiency induces an up-regulation of 5-HT$_{1A}$ and 5-HT$_{1B}$ receptors across brain regions as well as a reduction of norepinephrine concentrations accompanied by a reduced number of noradrenergic neurons. Together, our results characterize developmental, neurochemical, neurobiological and electrophysiological consequences of brain-specific 5-HT deficiency, reveal a dual dose-dependent role of 5-HT in body weight regulation and show that differentiation of serotonergic neuron phenotype is independent from endogenous 5-HT synthesis