Caenorhabditis Elegans AMsh Glia Regulate Olfactory Adaptation In Real Time Via GABAergic Signaling

Glial cells are an important class of nerve cells.In addition to nutrition and support,glial cells play a vital role in neuronal development and synaptic transmission.In recent years,more and more studies have found that besides relatively long-term functions,glial cells can also be activated by a variety of signals,exhibit calcium responses,and regulate neuronal activity in real time,thereby influence the behavioral output.As a model animal commonly used in olfactory research,Caenorhabditis elegans(C.elegans)has a relatively simple but complete nervous system.Our study found that amphid sheath glia(AMsh glia),which envelop sensory neuronal receptive endings in the head of nematodes,were able to sense aversive odors with their own G protein-coupled receptors and produce calcium elevation.ASH neurons are the most important neurons for nematodes to sense aversive stimuli.Interestingly,the G protein-coupled receptors that AMsh glial cells depend on are different from which ASH neuron relies on.Combining manipulation methods such as optogenetics,pharmacology,and pharmacogenetics,as well as detection techniques like in vivo calcium imaging and behavioral studies,we found that upon activation,the AMsh glia suppress aversive odorants-triggered avoidance and promote olfactory adaptation by inhibiting ASH in real time via GABA signaling.Thus,we propose a two-receptor model where the glia and sensory neuron jointly mediate adaptive olfactory avoidance.In addition,we cultured rat glia-like cells in the nasal mucosa in vitro,and observed that these olfactory sustentacular cells can also be activated by aversive odors to produce calcium responses.These studies underscore a previously unknown active role of glia in olfaction,which may provide new insights into the glialike sustentacular cells in mammalian sensory transduction.The development of nervous system requires precise control to establish functional neuronal connectivity.Although several related processes in central nerve systems,such as synapse formation and subsequent pruning,have been well documented,the underlying regulatory mechanism in periphery nerve system remains elusive.Here,we report that Drosophila macrophages,also called hemocytes,orderly migrate followed the route of ventral nerve cord development.Localized with the marker of neuromuscular junctions,HRP,hemocytes were observed engulfing NMJs structures spontaneously in third instar larvae.Ablation of hemocyte decreases the number of large synaptic boutons,while increases immature ghost boutons and active zones in large boutons.Meanwhile,depletion of hemocyte also decreases amplitude of excitatory junctional potentials while increases the frequency of miniature excitatory junctional potentials without affect its amplitude,accompanied by an ascent in the paired-pulse ratio.Furthermore,loss of hemocytes induces locomotion behavior defects in third instar larvae.Taken together,our results suggest that hemocytes regulate the morphologic and functional development of Drosophila NMJs by controlling the ratio of large synaptic boutons and associated electrophysiological activities,and finally influence the behavioral outputs of Drosophila larvae.