Astrocyte-like glial cells are abundant in the central nervous system of adult Drosophila and exhibit morphology similar to astrocytes of mammals. Previous evidence has shown that astrocyte-like glial cells are strongly associated with synapses in the antennal lobe (AL), the first relay of the olfactory system, where olfactory receptor neurons (ORNs) transmit information into projection neurons (PNs). However, the function of astrocyte-like glia in the AL remains obscure. In this study, using in vivo calcium imaging, we found that astrocyte-like glial cells exhibited spontaneous microdomain calcium elevations. Using simultaneous manipulation of glial activity and monitoring of neuronal function, we found that the astrocyte-like glial activation, but not ensheathing glial activation, could inhibit odor-evoked responses of PNs. Ensheathing glial cells are another subtype of glia, and are of functional importance in the AL. Electrophysiological experiments indicated that astrocyte-like glial activation decreased the amplitude and slope of excitatory postsynaptic potentials evoked through electrical stimulation of the antennal nerve. These results suggest that astrocyte-like glial cells may regulate olfactory processing through negative regulation of ORN-PN synaptic strength. Beyond the antennal lobe we observed astrocyte-like glial spontaneous calcium activities in the ventromedial protocerebrum, indicating that astrocyte-like glial spontaneous calcium elevations might be general in the adult fly brain. Overall, our study demonstrates a new function for astrocyte-like glial cells in the physiological modulation of olfactory information transmission, possibly through regulating ORN-PN synapse strength.

An injury to the spinal cord results in a crucial central nervous system event that further causes irreversible impairment or loss of motor, autonomic, and sensory functions. A progressive pathophysiological cascade following spinal cord injury (SCI) includes ischemia/reperfusion injury, oxidative stress, proapoptotic signaling, peripheral inflammatory cell infiltration, and glutamate-mediated excitotoxicity, and regulated cell death. These complex pathological and physiological changes continue to cause cell injury over the long-term and severely limit the efficacy of clinical treatment strategies in restoring the injured nervous system. Ferroptosis is a nonapoptotic, iron-regulated kind of cell death that has recently been discovered. It is distinguished by iron overload-induced toxic lipid peroxidation associated with mitochondrial morphological changes during the cell death process. For example, after SCI, iron overload activates the reactive oxygen species generation, dysregulation of glutathione/glutathione peroxidase 4 (GSH/GPX4) metabolism, and accumulation of lipid peroxides, which cause lipid membrane deterioration and ferroptosis. Conversely, knockout or differential expression of key genes and application of lipid peroxidation inhibitors and iron chelators (e.g., deferoxamine) (e.g., SRS-16-86) can block ferroptosis and promote neuronal repair for functional recovery after SCI. Although the findings of numerous investigations have been confirmed the importance of ferroptosis in several human neurologic sicknesses and its potential in SCI, the mechanism of ferroptosis and its application in SCI has not been elucidated. This review highlights current ferroptosis research and its impact on SCI, as well as the key molecular mechanism of ferroptosis in promoting the recovery from SCI. Understanding ferroptosis’ process and function in SCI could provide useful insight into the treatment and avoidance of such a destructive injury.

21In Drosophila melanogaster, mushroom body and anterior paired lateral (APL) neurons play im-22 portant roles not only in learning and memory but also in high cognitive behavior, reversal learn-23 ing. The circuit between APL neurons and Kenyon cells (KCs) in the mushroom body underlies 24 this behavior, including reversal learning, and electron microscopy (EM) methods must be used to 25 reveal this circuit. Here, we reconstructed the connections between mushroom body cells and APL 26 neurons in the vertical lobe of the mushroom body via focused ion beam scanning electron mi-27 croscopy (FIB-SEM) and sparse genetic horseradish peroxidase (HRP) labeling. We offer the first 28 EM evidence that recurrent network and lateral inhibition connections exist between APL neurons 29 and KCs in the vertical lobe of the mushroom body. This circuit is the neural basis of action selec-30 tion decision making, associative learning and reversal learning. Additionally, dopamine neurons 31 project to different areas of mushroom bodies and, together with extrinsic neurons and KC axons, 32 form a compartmental structure of mushroom body axons, thereby restricting the KC-mushroom 33 body output neuron (MBON) response to local compartments. Whether APL neurons also respond 34 locally is uncertain. We found that APL neurons exhibited input and output synapses that were 35 intermixed and arranged on enlarged and thin sections, respectively, resembling a string of beads. 36 Different KCs were found to project to APL neurons nonrepetitively, forming a local circuit struc-37 ture. Furthermore, using a single neurite calcium imaging method, we identified local calcium 38 domains on this circuit, suggestive of individual electrical compartments. The electrically recorded 39 APL neurons were nonspike neurons that selectively responded to odor in both the lobes and calyx. 40 Thus, the localized APL neuron responses coordinate with mushroom body-dopamine-MBON 41 compartmental function. 42 mushroom bodies in the MBON-β2β′2a pathway to mediate 3-h anesthesia-sensitive memory 65 (Pitman et al., 2011; Yang et al., 2016). 66 Some neuromodulator neurons innervate mushroom bodies, and dopaminergic neurons might 67 mediate unconditional stimuli, such as reward and punishment during learning. Dopamine neurons 68 couple with KCs, which encode odor information for conditioning, learning and storage of olfac-69 tory information. 70 Dopaminergic and extrinsic neurons have been shown to project to different areas of mushroom 71 body lobes and separate mushroom bodies into 15 functional compartments (Aso et al., 2014a, 72 2014b). The dopamine neurons that project locally encode innate states as well as external experi-73 ences. Together with KC axons and extrinsic neurons, the locally projecting dopamine neurons 74 form local information circuits in this area (Cohn, Morantte, & Ruta, 2015), dopamine neurons 75 constrain KC neuron responding locally. 76 Studies on APL neuron morphology have shown that these neurons innervate whole lobes and 77 the calyx (Liu &...