Empowering Smart Aging: Insights into the Technical Architecture of the e-VITA Virtual Coaching System for Older Adults.

With a substantial rise in life expectancy throughout the last century, society faces the imperative of seeking inventive approaches to foster active aging and provide adequate aging care. The e-VITA initiative, jointly funded by the European Union and Japan, centers on an advanced virtual coaching methodology designed to target essential aspects of promoting active and healthy aging. This paper describes the technical framework underlying the e-VITA virtual coaching system platform and presents preliminary feedback on its use. At its core is the e-VITA Manager, a pivotal component responsible for harmonizing the seamless integration of various specialized devices and modules. These modules include the Dialogue Manager, Data Fusion, and Emotional Detection, each making distinct contributions to enhance the platform's functionalities. The platform's design incorporates a multitude of devices and software components from Europe and Japan, each built upon diverse technologies and standards. This versatile platform facilitates communication and seamless integration among smart devices such as sensors and robots while efficiently managing data to provide comprehensive coaching functionalities.

Interaction with a Virtual Coach for Active and Healthy Ageing.

Since life expectancy has increased significantly over the past century, society is being forced to discover innovative ways to support active aging and elderly care. The e-VITA project, which receives funding from both the European Union and Japan, is built on a cutting edge method of virtual coaching that focuses on the key areas of active and healthy aging. The requirements for the virtual coach were ascertained through a process of participatory design in workshops, focus groups, and living laboratories in Germany, France, Italy, and Japan. Several use cases were then chosen for development utilising the open-source Rasa framework. The system uses common representations such as Knowledge Bases and Knowledge Graphs to enable the integration of context, subject expertise, and multimodal data, and is available in English, German, French, Italian, and Japanese.

Optogenetic activation of mGluR1 signaling in the cerebellum induces synaptic plasticity.

Neuronal plasticity underlying cerebellar learning behavior is strongly associated with type 1 metabotropic glutamate receptor (mGluR1) signaling. Activation of mGluR1 leads to activation of the Gq/11 pathway, which is involved in inducing synaptic plasticity at the parallel fiber-Purkinje cell synapse (PF-PC) in form of long-term depression (LTD). To optogenetically modulate mGluR1 signaling we fused mouse melanopsin (OPN4) that activates the Gq/11 pathway to the C-termini of mGluR1 splice variants (OPN4-mGluR1a and OPN4-mGluR1b). Activation of both OPN4-mGluR1 variants showed robust Ca2+ increase in HEK cells and PCs of cerebellar slices. We provide the prove-of-concept approach to modulate synaptic plasticity via optogenetic activation of OPN4-mGluR1a inducing LTD at the PF-PC synapse in vitro. Moreover, we demonstrate that light activation of mGluR1a signaling pathway by OPN4-mGluR1a in PCs leads to an increase in intrinsic activity of PCs in vivo and improved cerebellum driven learning behavior.

Separable gain control of ongoing and evoked activity in the visual cortex by serotonergic input.

Controlling gain of cortical activity is essential to modulate weights between internal ongoing communication and external sensory drive. Here, we show that serotonergic input has separable suppressive effects on the gain of ongoing and evoked visual activity. We combined optogenetic stimulation of the dorsal raphe nucleus (DRN) with wide-field calcium imaging, extracellular recordings, and iontophoresis of serotonin (5-HT) receptor antagonists in the mouse visual cortex. 5-HT1A receptors promote divisive suppression of spontaneous activity, while 5-HT2A receptors act divisively on visual response gain and largely account for normalization of population responses over a range of visual contrasts in awake and anesthetized states. Thus, 5-HT input provides balanced but distinct suppressive effects on ongoing and evoked activity components across neuronal populations. Imbalanced 5-HT1A/2A activation, either through receptor-specific drug intake, genetically predisposed irregular 5-HT receptor density, or change in sensory bombardment may enhance internal broadcasts and reduce sensory drive and vice versa.

CaMello-XR enables visualization and optogenetic control of Gq/11 signals and receptor trafficking in GPCR-specific domains.

The signal specificity of G protein-coupled receptors (GPCRs) including serotonin receptors (5-HT-R) depends on the trafficking and localization of the GPCR within its subcellular signaling domain. Visualizing traffic-dependent GPCR signals in neurons is difficult, but important to understand the contribution of GPCRs to synaptic plasticity. We engineered CaMello (Ca2+-melanopsin-local-sensor) and CaMello-5HT2A for visualization of traffic-dependent Ca2+ signals in 5-HT2A-R domains. These constructs consist of the light-activated Gq/11 coupled melanopsin, mCherry and GCaMP6m for visualization of Ca2+ signals and receptor trafficking, and the 5-HT2A C-terminus for targeting into 5-HT2A-R domains. We show that the specific localization of the GPCR to its receptor domain drastically alters the dynamics and localization of the intracellular Ca2+ signals in different neuronal populations in vitro and in vivo. The CaMello method may be extended to every GPCR coupling to the Gq/11 pathway to help unravel new receptor-specific functions in respect to synaptic plasticity and GPCR localization.