Our access to computer-generated worlds changes the way we feel, how we think, and how we solve problems. In this review, we explore the utility of different types of virtual reality, immersive or non-immersive, for providing controllable, safe environments that enable individual training, neurorehabilitation, or even replacement of lost functions. The neurobiological effects of virtual reality on neuronal plasticity have been shown to result in increased cortical gray matter volumes, higher concentration of electroencephalographic beta-waves, and enhanced cognitive performance. Clinical application of virtual reality is aided by innovative brain–computer interfaces, which allow direct tapping into the electric activity generated by different brain cortical areas for precise voluntary control of connected robotic devices. Virtual reality is also valuable to healthy individuals as a narrative medium for redesigning their individual stories in an integrative process of self-improvement and personal development. Future upgrades of virtual reality-based technologies promise to help humans transcend the limitations of their biological bodies and augment their capacity to mold physical reality to better meet the needs of a globalized world.

Bexarotene-activated retinoid X receptors (RXRs) ameliorate memory deficits in Alzheimer9s disease mouse models, including mice expressing human apolipoprotein E (APOE) isoforms. The goal of this study was to gain further insight into molecular mechanisms whereby ligand-activated RXR can affect or restore cognitive functions. We used an unbiased approach to discover genome-wide changes in RXR cistrome (ChIP-Seq) and gene expression profile (RNA-Seq) in response to bexarotene in the cortex of APOE4 mice. Functional categories enriched in both datasets revealed that bexarotene-liganded RXR affected signaling pathways associated with neurogenesis and neuron projection development. To further validate the significance of RXR for these functions, we used mouse embryonic stem (ES) cells, primary neurons, and APOE3 and APOE4 mice treated with bexarotene. In vitro data from ES cells confirmed that bexarotene-activated RXR affected neuronal development at different levels, including proliferation of neural progenitors and neuronal differentiation, and stimulated neurite outgrowth. This effect was validated in vivo by demonstrating an increased number of neuronal progenitors after bexarotene treatment in the dentate gyrus of APOE3 and APOE4 mice. In primary neurons, bexarotene enhanced the dendritic complexity characterized by increased branching, intersections, and bifurcations. This effect was confirmed by in vivo studies demonstrating that bexarotene significantly improved the compromised dendritic structure in the hippocampus of APOE4 mice. We conclude that bexarotene-activated RXRs promote genetic programs involved in the neurogenesis and development of neuronal projections and these results have significance for the improvement of cognitive deficits. SIGNIFICANCE STATEMENT Bexarotene-activated retinoid X receptors (RXRs) ameliorate memory deficits in Alzheimer9s disease mouse models, including mice expressing human apolipoprotein E (APOE) isoforms. The goal of this study was to gain further insight into molecular mechanisms whereby ligand-activated RXR can affect or restore cognitive functions. We used an unbiased approach to discover genome-wide changes in RXR cistrome (ChIP-Seq) and gene expression profile (RNA-Seq) in response to bexarotene in the cortex of APOE4 mice. Functional categories enriched in both datasets revealed that liganded RXR affected signaling pathways associated with neurogenesis and neuron projection development. The significance of RXR for these functions was validated in mouse embryonic stem cells, primary neurons, and APOE3 and APOE4 mice treated with bexarotene.