A Programmable Ontology Encompassing the Functional Logic of the Drosophila Brain

Abstract

The Drosophila brain has only a fraction of the number of neurons of higher organisms such as mice and humans. Yet the sheer complexity of its neural circuits recently revealed by large connectomics datasets suggests that computationally modeling the function of fruit fly brain circuits at this scale poses significant challenges. To address these challenges, we present here a programmable ontology that expands the scope of the current Drosophila brain anatomy ontologies to encompass the functional logic of the fly brain. The programmable ontology provides a language not only for modeling circuit motifs but also for programmatically exploring their functional logic. To achieve this goal, we tightly integrated the programmable ontology with the workflow of the interactive FlyBrainLab computing platform. As part of the programmable ontology, we developed NeuroNLP++, a web application that supports free-form English queries for constructing functional brain circuits fully anchored on the available connectome/synaptome datasets, and the published worldwide literature. In addition, we present a methodology for including a model of the space of odorants into the programmable ontology, and for modeling olfactory sensory circuits of the antenna of the fruit fly brain that detect odorant sources. Furthermore, we describe a methodology for modeling the functional logic of the antennal lobe circuit consisting of a massive number of local feedback loops, a characteristic feature observed across Drosophila brain regions. Finally, using a circuit library, we demonstrate the power of our methodology for interactively exploring the functional logic of the massive number of feedback loops in the antennal lobe.

Divisive normalization processors in the early visual system of the Drosophila brain

“…This type of MIMO circuit architecture has been observed in many neural systems (Lazar et al. 2022b ).…”

The functional logic of odor information processing in the Drosophila antennal lobe

“…A partial validation of the connectivity structure of the graphs underlying the model circuits of the current work can be obtained from a detailed mapping the LN pathways into the available connectomics datasets [ 31 , 32 ]. For the three LN pathways modeled here, neurons corresponding to the Global Pre-LN have been reported [ 32 , 54 , 55 ] (e.g., Broad Trio in larval AL [ 32 ]), and excitatory Post-LNs have also been previously reported in [ 33 ]. However, accurate mapping of our model to the “wetware” of biological brains would require comparative analyses of multiple connectomics dataset with synaptic information including neurotransmitter profile—a task for which the current work provides a hypothetical scaffolding.…”

“…Furthermore, the LN cell-types are assumed to be either pan-glomerular or uni-glomerular, while many LNs in the AL innervate a subset of the glomeruli. Nevertheless, the circuit models presented herein can be readily extended to incorporate these neuron types, and we are actively working on bridging the gap between computational AL models and biological data [ 54 , 55 ].…”