The assembly of population coding networks

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PROJECT SUMMARY Population coding is a fundamental strategy that the nervous system employs to represent sensory stimulus and generate perception. In neural networks that perform population coding (termed “population coding networks (PCNs)”), input-elicited responses are quantitatively heterogeneous across neurons and the response of a single neuron does not sufficiently define the stimulus; instead, the computed response of the entire population of neurons underlies the perception of the stimulus. Despite the importance of PCNs, very little is known about how they are assembled during development. The objective of the proposed research is to identify the mechanisms that establish a PCN during development. In many PCNs, the constituent neurons are not distinguishable from each other, except by their heterogeneous physiological properties. While the apparent homogeneity of these PCNs ensures that constituent neurons contribute to the same brain function, it also poses a challenge for studying the molecular and cellular mechanisms that underlie the assembly of PCNs. A recent study reported a neural network that encodes the intensity of noxious inputs through population coding in Drosophila larvae, which offers an excellent system for studying PCN assembly. Preliminary results suggest that Hox genes are involved in establishing this PCN. The central hypothesis is that a post-mitotic Hox code specifies the synaptic inputs to different neurons along the A-P axis, establishing a population-coding network that encodes stimulus intensity. This hypothesis will be tested by identifying the cellular (Aim 1) and molecular (Aim 2) mechanisms that establish the heterogeneity of the neurons in this PCN. The proposed research is innovative because it proposes novel cellular and molecular mechanisms that generate quantitative heterogeneity in a neural network. Moreover, it will use a newly developed technique that is ideally suited for studying neuronal population activity in the PCN. Novel genetic tools have also been developed for accessing subpopulation of neurons in the PCN. This research is significant because it will provide cellular, molecular, and conceptual insights into the establishment of other PCNs in Drosophila and other species. Beyond the PCNs, it will inform how physiological heterogeneity arises in a seemingly identical group of neurons. Furthermore, the successful completion of the proposed study will also demonstrate a Hox-based matching system that establish neuronal connections confined to specific rostrocaudal segments.