Liqun Luo, PhD

Department of Biology
Stanford University and Howard Hughes Medical Institute
(October 5, 2015)

Organization and Assembly of the Olfactory Systems

Studying the human brain and its billions of neurons and synapses can be an overwhelming prospect. Studying smaller brains, such as the fruit fly or mouse, can offer insights into the development and function of the more complex human brain. Dr. Luo, in his two lectures, discussed methods of tracking neuronal connections between areas of the brain. His lab focuses on the olfactory system specifically, as a model of how the rest of the brain develops precise neuronal circuitry.

The human brain contains ~1011 neurons, each making ~103 synapses with other neurons. These 1014 synaptic connections enable us to sense, think, remember, and act. How is this vast number of neurons organized into circuits to process information? How are these circuits assembled during development? To address these questions, we use model neural circuits in the less numerically complex brains of the fruit fly (~105 neurons) and mouse (~108 neurons) and combine state-ofthe-art molecular genetics and viral techniques with physiological and behavioral approaches.

Recent advances in neuroscience have produced an impressive array of tools to genetically label, anatomically trace, physiologically record, and functionally perturb specific populations of neurons. However, these methods are mostly applicable to studying local circuits of neurons; information about their long-distance connections is lost. A bottleneck in understanding the brain is to decipher the global patterns of

neuronal connectivity. In the first talk, I described our recent development of viral-genetic tracing tools that enable systematic mapping of input, output, and input-output relationships of specific neuronal types in defined brain regions at the scale of the entire mouse brain. I used the locus coeruleus norepinephrine neurons and ventral tegmental area dopamine neurons as two examples to illustrate the utility of these methods in deciphering the circuit architecture of these key neuromodulatory systems.

The olfactory circuits of flies and mice share remarkable similarities and offer salient advantages for investigating their structure, function, and development. In the fly, olfactory receptor neurons (ORNs) expressing the same odorant receptor project their axons to the same glomeruli in the antennal lobe. Projection neurons (PNs) send dendrites to individual glomeruli and relay olfactory information via their axons to higherorder centers that mediate learned and innate olfactory behavior. The assembly of the fly olfactory system requires precise glomerular targeting of axons from each of the 50 ORN types and dendrites from each of the 50 PN types.

In the second talk, I focused on how wiring specificity is established during the assembly of the fly olfactory circuit. We found that PN dendrites pattern the antennal lobe prior to ORN axon arrival. Global graded cues and local binary determinants collaborate to pattern PN dendrites. ORN axon targeting also employs a multistep process involving trajectory choice, axon-axon repulsion,

and synap tic partner matching to establish one-to-one connections between cognate ORNs and PNs. The molecules and mechanisms used in the assembly of the fly olfactory circuit are likely generally used in different circuits and organisms from insects to mammals.