D'Alessandro, I. | Search bioRxiv

bioRxiv2020

Neural control of steering in walking Drosophila

Orienting behaviors provide a continuous stream of information about an organisms sensory experiences and plans. Thus, to study the links between sensation and action, it is useful to identify the neurons in the brain that control orienting behaviors. Here we describe descending neurons in the Drosophila brain that predict and influence orientation (heading) during walking. We show that these cells have specialized functions: whereas one cell type predicts sustained low-gain steering, the other predicts transient high-gain steering. These latter cells integrate internally-directed steering signals from the head direction system with stimulus-directed steering signals from multimodal sensory pathways. The inputs to these cells are organized to produce "see-saw" steering commands, so that increasing output from one brain hemisphere is accompanied by decreasing output from the other hemisphere. Together, our results show that internal and external drives are integrated to produce descending motor commands with different timescales, for flexible and precise control of an organisms orientation in space.

neuroscience↗

bioRxiv2020

Divergent ion selectivity and sensitivity to anti-hypertensive and non-steroidal anti-inflammatory drugs of DEG/ENaC/ASIC channels in C. elegans

The degenerin channels, epithelial sodium channels, and acid-sensing ion channels (DEG/ENaC/ASICs) play important roles in sensing mechanical stimuli, regulating salt homeostasis, and responding to acidification in the nervous system. They have two transmembrane domains separated by a large extracellular domain and are believed to assemble as homomeric or heteromeric trimers. Based on studies of selected family members, these channels are assumed to form non-voltage gated and sodium-selective channels sensitive to the anti-hypertensive drug, amiloride. They are also emerging as a target of nonsteroidal anti-inflammatory drugs (NSAIDs). C. elegans has more than two dozen genes encoding DEG/ENaC/ASIC subunits, providing an excellent opportunity to examine variations in drug sensitivity. Here, we analyze a subset of the C. elegans DEG/ENaC/ASIC proteins to test the hypothesis that individual family members vary not only in their ability to form homomeric channels, but also in their drug sensitivity. We selected five C. elegans DEG/ENaC/ASICs (DEGT-1, DEL-1, UNC-8, MEC-10 and MEC-4) that are co-expressed in mechanosensory neurons and expressed gain-of-function d mutant isoforms in Xenopus laevis oocytes. We found that only DEGT-1d, UNC-8d, and MEC-4d formed homomeric channels and that, unlike MEC-4d and UNC-8d, DEGT-1d channels were insensitive to amiloride and its analogs. As reported for rat ASIC1a, NSAIDs inhibit DEGT-1d and UNC-8d channels. Unexpectedly, MEC-4d was strongly potentiated by NSAIDs, an effect that was decreased by mutations in the putative NSAID binding site in the extracellular domain. Collectively, these findings reveal that not all DEG/ENaC/ASIC channels are amiloride-sensitive and that NSAIDs can both inhibit and potentiate these channels. SummaryAnimal physiology depends on degenerin, epithelial sodium, and acid-sensing ion channels (DEG/ENaC/ASICs). By measuring the sensitivity of three C. elegans DEG/ENaC/ASICs to five amiloride analogs and five NSAIDs, we show that individual channels have distinct pharmacological footprints.

biophysics↗