Increase in brain glycogen levels ameliorates Huntington's disease phenotype and rescues neurodegeneration in Drosophila.

Under normal physiological conditions, the mammalian brain contains very little glycogen, most of which is stored in astrocytes. However, the aging brain and the subareas of the brain in patients with neurodegenerative disorders tend to accumulate glycogen, the cause and significance of which remain largely unexplored. Using cellular models, we have recently demonstrated a neuroprotective role for neuronal glycogen and glycogen synthase in the context of Huntington's disease. To gain insight into the role of brain glycogen in regulating proteotoxicity, we utilized a Drosophila model of Huntington's disease, in which glycogen synthase is either knocked down or expressed ectopically. Enhancing glycogen synthesis in the brains of flies with Huntington's disease decreased mutant Huntingtin aggregation and reduced oxidative stress by activating auto-lysosomal functions. Further, overexpression of glycogen synthase in the brain rescues photoreceptor degeneration, improves locomotor deficits and increases fitness traits in this Huntington's disease model. We, thus, provide in vivo evidence for the neuroprotective functions of glycogen synthase and glycogen in neurodegenerative conditions, and their role in the neuronal autophagy process.

Combinatorial encoding of odors in the mosquito antennal lobe.

Among the cues that a mosquito uses to find a host for blood-feeding, the smell of the host plays an important role. Previous studies have shown that host odors contain hundreds of chemical odorants, which are detected by different receptors on the peripheral sensory organs of mosquitoes. But how individual odorants are encoded by downstream neurons in the mosquito brain is not known. We developed an in vivo preparation for patch-clamp electrophysiology to record from projection neurons and local neurons in the antennal lobe of Aedes aegypti. Combining intracellular recordings with dye-fills, morphological reconstructions, and immunohistochemistry, we identify different sub-classes of antennal lobe neurons and their putative interactions. Our recordings show that an odorant can activate multiple neurons innervating different glomeruli, and that the stimulus identity and its behavioral preference are represented in the population activity of the projection neurons. Our results provide a detailed description of the second-order olfactory neurons in the central nervous system of mosquitoes and lay a foundation for understanding the neural basis of their olfactory behaviors.