Neural circuits, composed of interconnected neurons, represent the basic unit of the nervous system. One way to understand the highly complex arrangement of cross-talking, serial and parallel circuits is to resolve its developmental and evolutionary emergence. The rationale of the research proposal presented here is to elucidate the complex circuitry of the vertebrate and insect forebrain by comparison to the much simpler and evolutionary ancient “connectome” of the marine annelid Platynereis dumerilii. We will build a unique resource, the Platynereis Neuron Type Atlas, combining, for the first time, neuronal morphologies, axonal projections, cellular expression profiling and developmental lineage for an entire bilaterian brain. We will focus on five days old larvae when most adult neuron types are already present in small number and large part of the axonal scaffold in place.
Building on the Neuron Type Atlas, the second part of the proposal envisages the functional dissection of the Platynereis chemosensory-motor forebrain circuits. A newly developed microfluidics behavioural assay system, together with a cell-based GPCR screening will identify partaking neurons. Zinc finger nuclease-mediated knockout of circuit-specific transcription factors as identified from the Atlas will reveal circuit-specific gene regulatory networks, downstream effector genes and functional characteristics. Laser ablation of GFP-labeled single neurons and axonal connections will yield further insight into the function of circuit components and subcircuits. Given the ancient nature of the Platynereis brain, this research is expected to reveal a simple, developmental and evolutionary “blueprint” for the olfactory circuits in mice and flies and to shed new light on the evolution of information processing in glomeruli and higher-level integration in sensory-associative brain centres.
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