Interindividual variability of neuronal connectivity and function in zebrafish olfactory bulb

Brains of different individuals perform common essential functions despite differences in character, skills, perception or learning abilities. These fundamental observations suggest that neuronal computations exhibit different degrees of invariance to natural variability in the structure and dynamics of neuronal circuits. To understand the relation between structural and functional variability in a complex sensory network we focus on the olfactory bulb (OB) of larval zebrafish. The OB is optically accessible and sufficiently small to enable dense ultrastructural reconstructions of neuronal circuitry by volume electron microscopy (EM) in multiple individuals. We first used 2-photon calcium imaging to bilaterally measure population activity evoked by multiple odors and subsequently acquired stacks of EM images covering both OBs to reconstruct neuronal morphologies and synaptic connectivity. We have obtained activity measurements and EM image stacks from multiple zebrafish larvae. EM images were aligned and pre-processed for automated segmentation of neurons. Somata were identified in EM and 2-photon datasets, and corresponding somata are mapped between datasets using a combination of image analysis tools. OBs can be aligned across individuals using glomeruli as anatomical landmarks. The reconstruction of neuronal morphologies and synapses in EM datasets is ongoing. Once completed, our correlated datasets will allow us to analyze the relation between circuit structure and function in unprecedented detail. For example, it will be possible to directly compare the variability and consistency of odor responses across OBs of the same and different individuals to variations in morphology, glomerular affiliations and synaptic connectivity of the same neurons.