CaVß-subunit dependence of forward and reverse trafficking of CaV1.2 calcium channels.

Auxiliary CaVß subunits interact with the pore forming CaVα1 subunit to promote the plasma membrane expression of high voltage-activated calcium channels and to modulate the biophysical properties of Ca2+ currents. However, the effect of CaVß subunits on channel trafficking to and from the plasma membrane is still controversial. Here, we have investigated the impact of CaVß1b and CaVß2a subunits on plasma membrane trafficking of CaV1.2 using a live-labeling strategy. We show that the CaVß1b subunit is more potent in increasing CaV1.2 expression at the plasma membrane than the CaVß2a subunit and that this effect is not related to modification of intracellular trafficking of the channel (i.e. neither forward trafficking, nor recycling, nor endocytosis). We conclude that the differential effect of CaVß subunit subtypes on CaV1.2 surface expression is likely due to their differential ability to protect CaV1.2 from degradation.

Experimentally induced limb-disownership in mixed reality.

The seemingly stable construct of our bodily self depends on the continued, successful integration of multisensory feedback about our body, rather than its purely physical composition. Accordingly, pathological disruption of such neural processing is linked to striking alterations of the bodily self, ranging from limb misidentification to disownership, and even the desire to amputate a healthy limb. While previous embodiment research has relied on experimental setups using supernumerary limbs in variants of the Rubber Hand Illusion, we here used Mixed Reality to directly manipulate the feeling of ownership for one's own, biological limb. Using a Head-Mounted Display, participants received visual feedback about their own arm, from an embodied first-person perspective. In a series of three studies, in independent cohorts, we altered embodiment by providing visuotactile feedback that could be synchronous (control condition) or asynchronous (400 ms delay, Real Hand Illusion). During the illusion, participants reported a significant decrease in ownership of their own limb, along with a lowered sense of agency. Supporting the right-parietal body network, we found an increased illusion strength for the left upper limb as well as a modulation of the feeling of ownership during anodal transcranial direct current stimulation. Extending previous research, these findings demonstrate that a controlled, visuotactile conflict about one's own limb can be used to directly and systematically modulate ownership - without a proxy. This not only corroborates the malleability of body representation but questions its permanence. These findings warrant further exploration of combined VR and neuromodulation therapies for disorders of the bodily self.