Synaptic and circuit mechanisms of olfactory processing

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Odor molecules are sensed by olfactory receptor neurons, which in turn send information about odor stimuli to the olfactory bulb (in vertebrates), or the antennal lobe (in insects). All the receptor neurons that express the same olfactory receptor gene send information to the same discrete region (glomerulus) in the brain. What happens next-when olfactory information is processed by neural circuits in the brain-is still poorly understood. One difficulty is the complexity of the olfactory circuit: each glomerulus contains recurrent excitatory and inhibitory neural circuits, and receives lateral connections from other glomeruli. Drosophila is a good model system for investigating this problem, given the range of genetic tools available in the fruit fly. Also, the fly olfactory system is broadly similar to that of vertebrates, but much simpler. This study examines how olfactory information is processed by the circuitry of the antennal lobe. In particular, these experiments will dissect the odor-evoked electrophysiological response of second-order olfactory neurons in the antennal lobe (termed projection neurons, or PNs), using specific genetic manipulations that destroy or rescue function in the sensory inputs targeting single glomeruli. In vivo whole-cell patch-clamp recordings will be used to assess PN responses to olfactory stimulation of the fly's antennae. Specific aim #1 asks whether both inhibitory and excitatory synapses between glomeruli contribute to odor-evoked activity in PNs. Aim #2 tests the hypothesis that inhibitory and/or excitatory synapses between glomeruli are both stereotyped and specific. Aim #3 investigates the contribution of synaptic interactions within each glomerulus to the specific features of odor-evoked activity in PNs. This project should contribute substantially to our understanding of the very first steps of olfactory processing in the brain. Understanding early olfactory coding should help in treating olfactory disorders in human patients, and could aid in understanding why these disorders are often early warning signs of neurodegenerative diseases. Furthermore, understanding how the brain encodes odors has contributed valuable insights to the design of so-called "artificial noses", sensors designed to detect and discriminate between specific volatile chemicals. These sensors have important applications in medical diagnosis and biodefense, and have shown particular promise in diagnosing stage 1 lung cancer by measuring the chemicals present in a subject's breath.