Interhemispheric connections enable interaction and integration of sensory information in bilaterian nervous systems and are thought to optimize sensory computations. However, the cellular and spatial organization of interhemispheric networks and the computational properties they mediate in vertebrates are still poorly understood. Thus, it remains unclear to what extent the connectivity between left and right brain hemispheres participates in sensory processing. Here, we show that the zebrafish olfactory bulbs (OBs) receive direct interhemispheric projections from their contralateral counterparts in addition to top-down inputs from the contralateral zebrafish homolog of olfactory cortex. The direct interhemispheric projections between the OBs reach peripheral layers of the contralateral OB and retain a precise topographic organization, which directly connects similarly tuned olfactory glomeruli across hemispheres. In contrast, interhemispheric top-down inputs consist of diffuse projections that broadly innervate the inhibitory granule cell layer. Jointly, these interhemispheric connections elicit a balance of topographically organized excitation and nontopographic inhibition on the contralateral OB and modulate odor responses. We show that the interhemispheric connections in the olfactory system enable the modulation of odor response and contribute to a small but significant improvement in the detection of a reproductive pheromone when presented together with complex olfactory cues by potentiating the response of the pheromone selective neurons. Taken together, our data show a previously unknown function for an interhemispheric connection between chemosensory maps of the olfactory system.

In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation. In keeping with the immotile nature of olfactory cilia, we observed that ciliary motility genes are repressed in zebrafish, mouse, and human OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the differentiation of the OSNs themselves by regulating their cell type-specific gene expression, such as that of olfactory marker protein (omp) involved in odor-evoked signal transduction. In line with this, response to bile acids, odors detected by OMP-positive OSNs, was significantly diminished in foxj1 mutant zebrafish. Taken together, our findings establish how the canonical Foxj1-mediated motile ciliogenic transcriptional program has been repurposed for the biogenesis of immotile olfactory cilia, as well as for the development of the OSNs.

Odors are initially represented in the olfactory bulb (OB) by patterns of sensory input across the array of glomeruli. Although activated glomeruli are often widely distributed, glomeruli responding to stimuli sharing molecular features tend to be loosely clustered and thus establish a fractured chemotopic map. Neuronal circuits in the OB transform glomerular patterns of sensory input into spatiotemporal patterns of output activity and thereby extract information about a stimulus. It is, however, unknown whether the chemotopic spatial organization of glomerular inputs is maintained during these computations. To explore this issue, we measured spatiotemporal patterns of odor-evoked activity across thousands of individual neurons in the zebrafish OB by temporally deconvolved two-photon Ca(2+) imaging. Mitral cells and interneurons were distinguished by transgenic markers and exhibited different response selectivities. Shortly after response onset, activity patterns exhibited foci of activity associated with certain chemical features throughout all layers. During the subsequent few hundred milliseconds, however, MC activity was locally sparsened within the initial foci in an odor-specific manner. As a consequence, chemotopic maps disappeared and activity patterns became more informative about precise odor identity. Hence, chemotopic maps of glomerular input activity are initially transmitted to OB outputs, but not maintained during pattern processing. Nevertheless, transient chemotopic maps may support neuronal computations by establishing important synaptic interactions within the circuit. These results provide insights into the functional topology of neural activity patterns and its potential role in circuit function.