Richard Axel, Columbia
Difference between representation and reality.
1300 ORN types random distribution in epithilium and converge on single distinct glomeruli. Additive activation of glomeruli to scents. 2p imaging in piriform cortex. Little overlap between cells in pirifom cortex to 2 different scents. Fly olfactory system 10^5 numerically simpler in fly. 80 OR types in fly, not homologous to mammlian system. Single OR per neuron + 1 fixed chaperone. ->protocerebrum. Convergence of common org between mam and fly. Individual ORN types project to single glomeruli. Axons that project from same glomeruli project to very similar arborizations in MB and protocerebrum, but different glomeruli projects are very different. Highly stereotyped circuit.
1. Is the map functional?
Express GCaMP line, take out brain, put in agar, puff odors for up to 6hr. Conserved patterns between animals. Some interneurons connect to every glomerulus. Excitation of PNs is specific. There is not rich interconnectivity between PNs. KO of Or43b specifically knocks out activity in a single glomerulus even though other glomeruli are activated by odors that normally activate both, shown with Ca and electrophysiology.
2. Can we correlate spatial patterns of neural activity with spatial outputs?
Stress flies, other flies will avoid the air from the tube of stressed flies (1960 Benzer).
dSO Avoidance is Mediated by OR42b and OR21a. One component of stress air is CO2, activates single V glomerulus. Very sensitive. Silencing Gr21a ORNs eliminates avoidance behavior. ChR2 light stim of Gr21a sensory neurons elicit avoidance. Necessary and sufficient. Glomerulus specific. Is this a special case or similar to other glomerular/activity?
Sexual behavior. Fruitless controls sexual behavior. Sex splice variants. Glomerulus larger in males. 67d neurons respond to male specific odor. KO males court males. KO females are less receptive to courtship. cVA Activates the DA1 Glomerulus. Use UV photoactivatable PA-GFP. Activate 1 glomerulus, see 6 PNs and the axon bundle. Instead, weakly activate glomerulus then strongly activate 1 slightly activated PN. Single DA1 PN responds to cVA. DA1 PNs Exhibit sexually dimorphic projections, and it is under control of fruitless gene. Express the opposite sex form of fruitless and the projection shifts to opposite sex.
3. Can we drive behavior by altering the structure of neuronal projections?
Now they ‘feminize’ 5 DA1 neurons in the brain with a DA specific opposite sex fruitless line. Now males court males. However, size does not matter. Mutant males also have the extra large ‘male sized’ DA glomerulus.
With associative behaviors, the complex interdigitation between projections in the protocerebrum may allow more complex integration…