Sperm guidance is controlled by chemical and physical cues. In many species, Ca(2+) bursts in the flagellum govern navigation to the egg. In Arbacia punctulata, a model system of sperm chemotaxis, a cGMP signaling pathway controls these Ca(2+) bursts. The underlying Ca(2+) channel and its mechanisms of activation are unknown. Here, we identify CatSper Ca(2+) channels in the flagellum of A. punctulata sperm. We show that CatSper mediates the chemoattractant-evoked Ca(2+) influx and controls chemotactic steering; a concomitant alkalization serves as a highly cooperative mechanism that enables CatSper to transduce periodic voltage changes into Ca(2+) bursts. Our results reveal intriguing phylogenetic commonalities but also variations between marine invertebrates and mammals regarding the function and control of CatSper. The variations probably reflect functional and mechanistic adaptations that evolved during the transition from external to internal fertilization.

The identity of cortical circuits mediating nociception and pain is largely unclear. The cingulate cortex is consistently activated during pain, but the functional specificity of cingulate divisions, the roles at distinct temporal phases of central plasticity and the underlying circuitry are unknown. Here we show in mice that the midcingulate division of the cingulate cortex (MCC) does not mediate acute pain sensation and pain affect, but gates sensory hypersensitivity by acting in a wide cortical and subcortical network. Within this complex network, we identified an afferent MCC-posterior insula pathway that can induce and maintain nociceptive hypersensitivity in the absence of conditioned peripheral noxious drive. This facilitation of nociception is brought about by recruitment of descending serotonergic facilitatory projections to the spinal cord. These results have implications for our understanding of neuronal mechanisms facilitating the transition from acute to long-lasting pain.

The sea urchin sperm guanylyl cyclase chemoreceptor achieves ultrasensitive signal detection and precise signal modulation through high receptor density, subnanomolar ligand affinity, and sequential dephosphorylation.

Highlights d Reactive astrocytes remodel perivascular mitochondrial and ER networks in vivo d Mfn2 deletion disrupts astrocytic mitochondria-ER contact sites and calcium buffering d Mfn2 deletion in astrocytes prevents injury-induced vascular remodeling d Perivascular enrichment of mitochondria-ER contact sites restores vascular remodeling

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Neocortico-thalamo-cortical loops represent a common, yet poorly understood, circuit employing giant synapses also referred to as “class I”, giant, or driver synapses. Here, we characterize a giant synapse formed by projection neurons of the paleocortical piriform cortex (PIR) onto neurons of the mediodorsal thalamus (MD). Three-dimensional (3D) ultrastructure of labeled PIR-MD terminals, obtained by using serial-section scanning electron microscopy (EM) combined with photooxidation-based detection of labeled terminals, revealed a large terminal engulfing multiple postsynaptic dendritic excrescences. The terminal contained multiple synaptic contacts, a high density of synaptic vesicles and several central mitochondria. Using targeted stimulations of single identified PIR-MD terminals in combination with patch-clamp recordings from the connected MD neuron, we found large postsynaptic currents with fast kinetics and strong short-term depression, yet fast recovery upon repetitive stimulation. We conclude that the phylogenetically old paleocortex already developed giant synaptic connections exhibiting similar functional properties as connections formed by giant neocortico-thalamic projections.

Astrocytes have emerged for playing key roles in tissue remodeling during brain repair, however the underlying mechanisms remain poorly understood. We show that acute injury and blood-brain barrier disruption trigger the formation of a prominent mitochondrial-enriched compartment in astrocytic end-feet which enables vascular recovery. Integrated imaging approaches revealed that this mitochondrial clustering is part of a metabolic adaptive response regulated by fusion dynamics.Astrocyte-specific deletion of Mitofusin 2 (Mfn2) suppressed perivascular mitochondrial remodeling and altered mitochondria-endoplasmic reticulum tethering domains. Functionally, two-photon imaging experiments showed that these structural changes were mirrored by impaired mitochondrial Ca 2+ uptake leading to abnormal cytosolic transients in astrocytic end-feet in vivo. At the tissue level, a severely compromised microvasculature in the lesioned area was rescued by boosting mitochondrial perivascular clustering in MFN2-deficient astrocytes. These data unmask a crucial role for astrocyte mitochondrial dynamics in regulating local metabolic signaling and have important implications for repairing the injured brain.

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