Genetically encoded biosensors of metabolic function for the study of neurodegeneration, a review and perspective.

Nervous system tissue is the most metabolically active in the body and neurons are the primary consumers of oxygen and metabolites in nervous tissue. Many processes support neuronal metabolism, and dysregulation of these processes or intrinsic neuronal metabolism is often tied to neurodegenerative diseases. While many techniques are available to query metabolic function and disease (e.

Identification of a natively resilient but poorly regenerating retinal ganglion cell type in the G protein-coupled receptor 88-Cre transgenic mouse.

Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss. In mice, there are 46 transcriptionally unique retinal ganglion cell types that demonstrate different susceptibilities to degeneration. Recent transcriptional experiments defined a novel retinal ganglion cell type that survives particularly well and uniquely expresses high levels of the orphan G-protein-coupled receptor 88.

Energetic diversity in retinal ganglion cells is modulated by neuronal activity and correlates with resilience to degeneration.

Neuronal function requires high energy expenditure that is likely customized to meet specific signaling demands. However, little is known about diversity of metabolic homeostasis among divergently-functioning types of neurons. To this end, we examined retinal ganglion cells (RGCs), a population of closely related, yet electrophysiologically distinct excitatory projection neurons.

Mistargeted retinal axons induce a synaptically independent subcircuit in the visual thalamus of albino mice.

In albino mice and EphB1 knockout mice, mistargeted retinal ganglion cell axons form dense islands of axon terminals in the dorsal lateral geniculate nuclei (dLGN). The formation of these islands of retinal input depends on developmental patterns of spontaneous retinal activity. We reconstructed the microcircuitry of the activity-dependent islands and found that the boundaries of the island represent a remarkably strong segregation within retinogeniculate connectivity.

Mistargeted retinal axons induce a synaptically independent subcircuit in the visual thalamus of albino mice.

In albino mice and EphB1 knock out mice, mistargeted retinal ganglion cell (RGC) axons form dense islands of axon terminals in the dorsal lateral geniculate nuclei (dLGN). The formation of these islands of retinal input depends on developmental patterns of spontaneous retinal activity. We reconstructed the microcircuitry of the activity dependent islands and found that the boundaries of the island represent a remarkably strong segregation within retinogeniculate connectivity.

Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo.

Retinal ganglion cell (RGC) degeneration drives vision loss in blinding conditions. RGC death is often triggered by axon degeneration in the optic nerve. Here, we study the contributions of dynamic and homeostatic Ca levels to RGC death from axon injury.

Galactosylated hydroxyl-polyamidoamine dendrimer targets hepatocytes and improves therapeutic outcomes in a severe model of acetaminophen poisoning-induced liver failure.

Toxicity to hepatocytes caused by various insults including drugs is a common cause of chronic liver failure requiring transplantation. Targeting therapeutics specifically to hepatocytes is often a challenge since they are relatively nonendocytosing unlike the highly phagocytic Kupffer cells in the liver. Approaches that enable targeted intracellular delivery of therapeutics to hepatocytes have significant promise in addressing liver disorders.

Cell-type-specific binocular vision guides predation in mice.

Predators use vision to hunt, and hunting success is one of evolution's main selection pressures. However, how viewing strategies and visual systems are adapted to predation is unclear. Tracking predator-prey interactions of mice and crickets in 3D, we find that mice trace crickets with their binocular visual fields and that monocular mice are poor hunters.

Transpupillary Two-photon In vivo Imaging of the Mouse Retina.

The retina transforms light signals from the environment into electrical signals that are propagated to the brain. Diseases of the retina are prevalent and cause visual impairment and blindness. Understanding how such diseases progress is critical to formulating new treatments.