Editorial: Insights in cellular neurophysiology: 2022

This Research Topic invited Frontiers Editors to highlight significant challenges and recent accomplishments in the neuroscientific field and highlight future directions. Seven contributions were gathered, including original articles, a review, and a methods report

The Drosophila melanogaster Na+/Ca2+ Exchanger CALX Controls the Ca2+ Level in Olfactory Sensory Neurons at Rest and After Odorant Receptor Activation

CALX, the Na+/Ca2+ exchanger in Drosophila, is highly expressed in the outer dendrites of olfactory sensory neurons (OSNs) which are equipped with the odorant receptors (ORs). Insect OR/Orco dimers are nonselective cation channels that pass also calcium which leads to elevated calcium levels after OR activation. CALX exhibits an anomalous regulation in comparison to its homolog in mammals sodium/calcium exchanger, NCX: it is inhibited by increasing intracellular calcium concentration [Ca2+]i. Thus, CALX mediates only Ca2+ efflux, not influx. The main goal of this study was to elucidate a possible role of this protein in the olfactory response. We first asked whether already described NCX inhibitors were capable of blocking CALX. By means of calcium imaging techniques in ex-vivo preparations and heterologous expression systems, we determined ORM-10962 as a potent CALX inhibitor. CALX inhibition did not affect the odor response but it affected the recovery of the calcium level after this response. In addition, CALX controls the calcium level of OSNs at rest

The Satiety Signaling Neuropeptide Perisulfakinin Inhibits the Activity of Central Neurons Promoting General Activity

The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK) in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK) in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR), we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM) neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM) due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH): PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage

Phosphorylation via PKC Regulates the Function of the Drosophila Odorant Co-Receptor

Insect odorant receptors (ORs) have a unique design of heterodimers formed by an olfactory receptor protein and the ion channel Orco. Heterologously expressed insect ORs are activated via an ionotropic and a metabotropic pathway that leads to cAMP production and activates the Orco channel. The contribution of metabotropic signaling to the insect odor response remains to be elucidated. Disruption of the Gq protein signaling cascade reduces the odor response (Kain et al., 2008). We investigated this phenomenon in HEK293 cells expressing Drosophila Orco and found that phospholipase C (PLC) inhibition reduced the sensitivity of Orco to cAMP. A similar effect was seen upon inhibition of protein kinase C (PKC), whereas PKC stimulation activated Orco even in the absence of cAMP. Mutation of the five PKC phosphorylation sites in Orco almost completely eliminated sensitivity to cAMP. To test the impact of PKC activity in vivo we combined single sensillum electrophysiological recordings with microinjection of agents affecting PLC and PKC function and observed an altered response of olfactory sensory neurons (OSNs) to odorant stimulation. Injection of the PLC inhibitor U73122 or the PKC inhibitor Gö6976 into sensilla reduced the OSN response to odor pulses. Conversely, injection of the PKC activators OAG, a diacylglycerol analog, or phorbol myristate acetate (PMA) enhanced the odor response. We conclude that metabotropic pathways affecting the phosphorylation state of Orco regulate OR function and thereby shape the OSN odor response

Towards plant-odor-related olfactory neuroethology in Drosophila

Drosophila melanogaster is today one of the three foremost models in olfactory research, paralleled only by the mouse and the nematode. In the last years, immense progress has been achieved by combining neurogenetic tools with neurophysiology, anatomy, chemistry, and behavioral assays. One of the most important tasks for a fruit fly is to find a substrate for eating and laying eggs. To perform this task the fly is dependent on olfactory cues emitted by suitable substrates as e.g. decaying fruit. In addition, in this area, considerable progress has been made during the last years, and more and more natural and behaviorally active ligands have been identified. The future challenge is to tie the progress in different fields together to give us a better understanding of how a fly really behaves. Not in a test tube, but in nature. Here, we review our present state of knowledge regarding Drosophila plant-odor-related olfactory neuroethology to provide a basis for new progress

Tuning Insect Odorant Receptors

Among the insect olfactory receptors the odorant receptors (ORs) evolved in parallel to the onset of insect flight. A special property of this receptor type is the capability to adjust sensitivity of odor detection according to previous odor contacts. This article presents a current view on regulatory processes affecting the performance of ORs and proposes a model of mechanisms contributing to OR sensitization

Functional and evolutionary aspects of chemoreceptors

The perception and processing of chemical signals from the environment is essential for any living systems and is most probably the first sense developed in life. This perspective discusses the physical limits of chemoreception and gives an overview on the receptor types developed during evolution to detect chemical signals from the outside world of an organism. It discusses the interaction of chemoreceptors with downstream signaling elements, especially the interaction between electrical and chemical signaling. It is further considered how the primary chemosignal is appropriately amplified. Three examples of chemosensory systems illustrate different strategies of such amplification