Testing the roles of motoneuron membrane currents for behaviorally adequate motor output by targeted genetic manipulations of an identified flight motoneuron in Drosophila

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The generation of patterned output from central neural circuits depends on synaptic connectivity and intrinsic membrane properties of the individual neurons. Motoneurons are the relays station between central pattern generating circuitry and muscles. Motoneurons are not mere followers of network input, but their intrinsic properties shape the final motor output. This project will use genetic tools available in Drosophila to unravel the ionic mechanisms underlying synaptic input integration and firing output of an identified motoneuron. The motoneuron’s ionic current bouquet will be described by in situ patch clamp analysis. Pharmacological and targeted genetic manipulations will be used to decipher which genes underlie each current (objective 1). Second, synaptic input integration and dendritic calcium signaling will be analyzed by in situ calcium imaging experiments (objective 2). These data will serve as bedrock to determine the roles of specific ion channels for shaping motoneuron output by combining targeted genetic manipulations in selected motoneurons with extracellular recordings in intact behaving animals (objective 3). Finally, modulation by biogenic amines is known to adjust motor patterns to changing requirements. This project will test whether biogenic amines directly modulate motoneuron ion channels and what the functional consequences are (objective 4). The highly conserved nature of ion channels makes similar functions in vertebrate motoneurons likely. Understanding normal motoneuron function is a prerequisite for addressing malfunction during diseases or after spinal cord injury.