As sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict this complexity is due to convergent inputs from neurons with diverse response properties, in most vertebrate systems convergence has only been inferred rather than tested directly. Here we measure sensory computations in zebrafish vestibular neurons across multiple axes in vivo. We establish that whole-cell physiological recordings reveal tuning of individual vestibular afferent inputs and their postsynaptic targets. An independent approach, serial section electron microscopy, supports the inferred connectivity. We find that afferents with similar or differing preferred directions converge on central vestibular neurons, conferring more simple or complex tuning, respectively. Our data also resolve a long-standing contradiction between anatomical and physiological analyses by revealing that sensory responses are produced by sparse but powerful inputs from vestibular afferents. Together these results provide a direct, quantifiable demonstration of feedforward input convergence in vivo.

We introduced and evaluated an end-to-end organs-at-risk (OARs) segmentation model that can provide accurate and consistent OARs segmentation results in much less time. Methods: We collected 105 patients' Computed Tomography (CT) scans that diagnosed locally advanced cervical cancer and treated with radiotherapy in one hospital. Seven organs, including the bladder, bone marrow, left femoral head, right femoral head, rectum, small intestine and spinal cord were defined as OARs. The annotated contours of the OARs previously delineated manually by the patient's radiotherapy oncologist and confirmed by the professional committee consisted of eight experienced oncologists before the radiotherapy were used as the ground truth masks. A multi-class segmentation model based on U-Net was designed to fulfil the OARs segmentation task. The Dice Similarity Coefficient (DSC) and 95th Hausdorff Distance (HD) are used as quantitative evaluation metrics to evaluate the proposed method. Results: The mean DSC values of the proposed method are 0.924, 0.854, 0.906, 0.900, 0.791, 0.833 and 0.827 for the bladder, bone marrow, femoral head left, femoral head right, rectum, small intestine, and spinal cord, respectively. The mean HD values are 5.098, 1.993, 1.390, 1.435, 5.949, 5.281 and 3.269 for the above OARs respectively. Conclusions: Our proposed method can help reduce the inter-observer and intra-observer variability of manual OARs delineation and lessen oncologists' efforts. The experimental results demonstrate that our model outperforms the benchmark U-Net model and the oncologists' evaluations show that the segmentation results are highly acceptable to be used in radiation therapy planning.

Motor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion is linked to both developmental sequence and neuronal temporal dynamics. Early-born pathways carrying phasic information preferentially excite fast escape circuits, whereas later-born pathways carrying tonic signals excite slower postural and oculomotor circuits. These results demonstrate that vestibular circuits are organized by tuning direction and dynamics, aligning them with downstream motor circuits and behaviors.

Biogenic amines are important signaling molecules, and the structural basis for their recognition by G Protein-Coupled Receptors (GPCRs) is well understood. Amines are also potent odors, with some activating olfactory trace amine-associated receptors (TAARs). Here, we report that teleost TAARs evolved a new way to recognize amines in a non-classical orientation. Chemical screens de-orphaned eleven zebrafish TAARs, with agonists including serotonin, histamine, tryptamine, 2-phenylethylamine, putrescine, and agmatine. Receptors from different clades contact ligands through aspartates on transmembrane α-helices III (canonical Asp3.32) or V (non-canonical Asp5.42), and diamine receptors contain both aspartates. Non-classical monoamine recognition evolved in two steps: an ancestral TAAR acquired Asp5.42, gaining diamine sensitivity, and subsequently lost Asp3.32. Through this transformation, the fish olfactory system dramatically expanded its capacity to detect amines, ecologically significant aquatic odors. The evolution of a second, alternative solution for amine detection by olfactory receptors highlights the tremendous structural versatility intrinsic to GPCRs.DOI: http://dx.doi.org/10.7554/eLife.10441.001