Title: Synaptic and circuit mechanisms of odor processing in Drosophila
Description: Sensory stimuli provide animals with important information about their environment. The precise mechanisms by which sensory information is transformed by neural circuits to guide behavior is a major question in neuroscience. In my work I have used the olfactory system of the fruit fly Drosophila melanogaster as a model for understanding the mechanistic underpinnings of sensory processing in the brain. This system is genetically hard-wired and numerically simple, which along with the powerful genetic tools available in the fly provide a unique opportunity for dissecting the synaptic and circuit mechanisms of odor representation and computation. Olfactory receptor neurons (ORNs) and their second-order targets, the projection neurons (PNs), are connected in glomerular compartments in the antennal lobe. Each glomerulus represents a parallel processing channel composed of just one type of ORN and PN. However, glomeruli are also interconnected by a rich set of local neurons. Most odors trigger distributed activity across multiple ORN types, and consequently, the determinants of PN receptive fields likely involve both direct ORN input and interglomerular interactions.

The goal of my work has been to separate the roles and identify the mechanisms of intra-versus inter-glomerular processing in the formation of PN receptive fields. I have used a combination of genetics, microdissections, electrophysiology, and pharmacology to address this issue. My strategy was to remove either direct or lateral input to a glomerulus and then investigate the consequences of these manipulations on PN odor responses. These experiments revealed the existence of both lateral excitatory and lateral inhibitory connections between glomeruli. Both lateral excitation and inhibition is distributed broadly across most, if not all, glomeruli in the antennal lobe. Lateral excitation is targeted postsynaptically onto the PN dendrite, whereas inhibition occurs predominately presynaptically at the ORN terminal and is mediated by both GABA A and GABA B receptors. Lateral excitation is very sensitive to weak ORN input, but saturates for stronger inputs. Lateral presynaptic inhibition, in contrast, continues to increase with stronger total input to the antennal lobe. This circuit design allows both high sensitivity for weak odors and prevents saturation of PN responses for strong odors.