Structure, Function and Input Pathways of Motion-sensitive Visual Interneurons in Drosophila melanogaster

Visual motion detection is of major importance for flies as they use the optic flow generated by their self-motion to control their course during flight. This so called optomotor behavior is thought to be controlled by a set of large-field motion-sensitive cells in the optic lobes called lobula plate tangential cells (LPTCs). LPTCs come in different variants and are tuned to different preferred directions. Their responses can be explained by assuming input from an array of local motion detectors of the correlation-type. In addition, they receive input from other LPTCs from both the ipsi- and the contralateral hemisphere. Response properties of LPTCs have been extensively described in large fly species. However, information about the presynaptic circuits that constitute the local motion detectors is still largely missing. Research on the fruit fly Drosophila promises to close this gap as it allows for combining physiological recordings from motion-sensitive cells with a genetic manipulation of the system. In that way the function of neurons too small for electrophysiological recordings can also be analyzed. Here, I provide important steps towards elucidating the cellular implementation of the correlation-type motion detector in the fly brain. First, I tested different genetically encoded Calcium indicators (GECIs) expressed in LPTCs by stimulating the neurons with potassium chloride. These experiments revealed that GECIs are functional in LPTCs and might thus be useful for monitoring neuronal activity in the visual system. Second, I described the response properties of HS (horizontal system) cells, a prominent subgroup of LPTCs in Drosophila. There are three HS cells per hemisphere, HSN, HSE and HSS. All of them are tuned to horizontal motion in a directionally selective way. I could show that their responses are indicative of correlation-type motion detectors providing input to them. In addition, they receive information from the contralateral side most likely via other LPTCs. HS cells not only have strongly overlapping dendritic trees in the lobula plate accounting for their large and overlapping receptive fields, but are also coupled electrically with each other. Extensive electrical connections can also be found to descending neurons in their output region in the central brain. This characterization of HS cells is important for two reasons: i) Their responses can be used as a read-out for the effects of manipulating the presynaptic motion detection circuitry in the fly by genetic techniques; ii) they can be correlated with behavioral reactions induced by horizontal motion to study how optomotor responses are controlled in the fly. Third, I studied the input pathways to the LPTCs in the lamina, the first optic neuropile after the compound eye. From all lamina cells, L1 and L2 are the most prominent neurons and were previously shown to provide the major input to the motion detection circuits. By genetically restoring synaptic input to either one of the two pathways I revealed that these two types of cells indeed provide the major input to LPTCs. However, their functional specialization for light increments and light decrements, disclosed by blocking their synaptic output, could not be revealed in these experiments. As L1 and L2 turned out to be electrically coupled with each other restoring the input to only one cell type also restores the input to the other one. Finally, I analyzed response properties of HS cells whose dendritic structure has been altered by overexpression of Dscam (Down syndrome cell adhesion molecule) during development. Dscam is a protein that comes in a large number of different isoforms and is thought to play a major role in self-recognition and thus proper dendritic and axonal branching. HS cells that misexpress a single isoform develop smaller and less overlapping dendritic trees in the lobula plate. These anatomical defects are accompanied by smaller receptive fields but otherwise normal motion responses. All these experiments show that the combination of physiological and genetic tools is a promising approach for dissecting neural circuits and gaining new insights into information processing in the brain. Continuation of this approach will hopefully bridge the gap between neurons of the lamina and the lobula plate by revealing the local motion detectors in the intermediate neuropile, the medulla