Conspecific chemosensory communication controls a broad range of social and sexual behaviors. In most mammals, social chemosignals are predominantly detected by sensory neurons of a specialized olfactory subsystem, the vomeronasal organ (VNO). The behavioral relevance of social chemosignaling puts high demands on the accuracy and dynamic range of the underlying transduction mechanisms. However, the physiological concepts implemented to ensure faithful transmission of social information remain widely unknown. Here, we show that sensory neurons in the basal layer of the mouse VNO dynamically control their input-output relationship by activitydependent regulation of K ϩ channel gene expression. Using large-scale expression profiling, immunochemistry, and electrophysiology, we provide molecular and functional evidence for a role of ether-à-go-go-related gene (ERG) K ϩ channels as key determinants of cellular excitability. Our findings indicate that an increase in ERG channel expression extends the dynamic range of the stimulus-response function in basal vomeronasal sensory neurons. This novel mechanism of homeostatic plasticity in the periphery of the accessory olfactory system is ideally suited to adjust VNO neurons to a target output range in a layer-specific and use-dependent manner.

Non-technical summary In mammalian testes, Sertoli cells play a key physiological role in germ cell development. Previous research has implicated local ATP release as a potential mechanism of Sertoli cell stimulation. We show that, in mouse Sertoli cells, two different receptor proteins are activated by ATP. Receptor activation, in turn, causes elevation of calcium ion levels inside the cells. By using a novel method to visualize such calcium signals, we identify mitochondria as essential elements of calcium regulation in the testis.Abstract Intimate bidirectional communication between Sertoli cells and developing germ cells ensures the integrity and efficiency of spermatogenesis. Yet, a conceptual mechanistic understanding of the physiological principles that underlie Sertoli cell autocrine and paracrine signalling is lacking. Here, we characterize a purinergic Ca 2+ signalling network in immature mouse Sertoli cells that consists of both P2X2 and P2Y2 purinoceptor subtypes, the endoplasmic reticulum and, notably, mitochondria. By combining a transgenic mouse model with a dedicated bioluminescence imaging device, we describe a novel method to monitor mitochondrial Ca 2+ mobilization in Sertoli cells at subcellular spatial and millisecond temporal resolution. Our data identify mitochondria as essential components of the Sertoli cell signalling 'toolkit' that control the shape of purinergic Ca 2+ responses, and probably several other paracrine Ca 2+ -dependent signals.

Male germ cell development takes place within the testes of mammals, but little is known about its regulation. Fleck et al. record from spermatogonia and Sertoli cells, both in vitro and in situ, and find evidence for P2X4- and P2X7-mediated ATP-gated currents as well as a Ca2+-activated BK conductance.

The mouse vomeronasal organ (VNO) plays a critical role in semiochemical detection and social communication. Vomeronasal stimuli are typically secreted in various body fluids. Following direct contact with urine deposits or other secretions, a peristaltic vascular pump mediates fluid entry into the recipient's VNO. Therefore, while vomeronasal sensory neurons (VSNs) sample various stimulatory semiochemicals dissolved in the intraluminal mucus, they might also be affected by the general physicochemical properties of the "solvent." Here, we report cycle stage-correlated variations in urinary pH among female mice. Estrus-specific pH decline is observed exclusively in urine samples from sexually experienced females. Moreover, patch-clamp recordings in acute VNO slices reveal that mouse VSNs reliably detect extracellular acidosis. Acid-evoked responses share the biophysical and pharmacological hallmarks of the hyperpolarizationactivated current I h . Mechanistically, VSN acid sensitivity depends on a pH-induced shift in the voltage-dependence of I h activation that causes the opening of HCN channels at rest, thereby increasing VSN excitability. Together, our results identify extracellular acidification as a potent activator of vomeronasal I h and suggest HCN channel-dependent vomeronasal gain control of social chemosignaling. Our data thus reveal a potential mechanistic basis for stimulus pH detection in rodent chemosensory communication.

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