Behaviors are quantitative traits, influenced by natural genetic variants in many different genes. Ultimately, polymorphisms impact the activity of single neurons to modify behavior. However, studies to dissect neuronal circuits are performed in a single genetic background, without the genetic context where they evolved. In this action, I propose to study neuronal activity in a more natural genetic context, by manipulating the activity of single neurons and measuring the resulting impact on behavior in several genetic backgrounds. This will allow determining how robust are neural circuits to genetic perturbation and identifying polymorphisms that modulate neuronal activity at the single neuron resolution.
To study the impact of genetic background in neuronal activity, I will use D.melanogaster which offer versatile genetic tools to manipulate activity of single neurons, resources for rapid analysis of population genetics and robust behavioral assays. One conserved behavior that flies share with many other species is the freeze or flee response to threats. Many aspects of this behavior have been dissected in flies, including the role of descending neurons (DNs), which connect the brain to motor centers. In here, I will inhibit the activity of DNs previously shown to impact the freezing behavior in response to looming stilmuli. This will be performed in several genetic backgrounds, using a collection of inbreed lines with fully sequenced genomes. With this, I will identify polymorphisms that interact with the action of single DNs, trough genome wide association study (GWAS). The candidate genes from this analysis will be tested for their role in modulating the neuronal activity.
NeuroContext will elucidate how genetic polymorphisms, present in natural populations, interact with the activity of single neurons. This will greatly impact the future research in neurosciences, by informing on how genetic backgrounds have to be considered in research programmes.
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