3. Organization and function of neural circuits in the mouse
We have combined rabies virus-mediated trans-synaptic tracing with mouse genetics to determine that the mouse olfactory cortex uses organizational principles similar to the fly olfactory system we described previously. To decipher neural circuit architecture at the scale of the entire mouse brain, we have recently developed viral genetic tools to trace the relationship between input and output (see Section 4 ). We have applied these tools to investigate the architecture of some of the most complex circuits in the mammalian brain—the monoamine systems, whose axons project broadly across the brain and whose importance to human health is reflected by the fact that most drugs for treating psychiatric disorders target these systems. We found the norepinephrine, dopamine, and serotonin systems employ distinct input–output architectures. For example, whereas populations of locus coeruleus norepinephrine neurons that project to a specific brain area also collateralize to all other areas we examined, dorsal raphe serotonin neurons that project to frontal cortex and amygdala have largely non-overlapping collateralization patterns, and exhibit distinct physiological response properties and behavioral functions. |
We are also combining genetic and circuit manipulation tools to investigate neural basis of thirst motivation, encoding properties of cerebellar granule cells, and communication between neocortex and cerebellum in the execution and learning of motor tasks.
|Fig. 5: Presynaptic partners of dorsal raphe serotonin neurons. Long-range input from frontal cortex and lateral habenula to dorsal raphe serotonin neurons revealed by rabies-mediated trans-synaptic tracing in this horizontal section of the mouse brain. For details, see Weissbourd B, Ren J, DeLoach KE et al. (2014) Neuron 83:645-662. |
Jefferis GSXE*, Potter CJ*, Chan AM, Marin EC, Rohlfing T, Maurer CR & Luo L (2007) Comprehensive maps of fly higher olfactory centres: spatially segregated fruit and pheromone representation. Cell 128:1187-1203.
Miyamichi K, Amat F, Moussavi F, Wang C, WIchersham I, Wall NR, Taniguchi H, Tasic B, Huang ZJ, He Z, Callaway EM, Horowitz MA & Luo L (2011) Cortical representations of olfactory input by trans-synaptic tracing. Nature 472:191-196.
Miyamichi K*, Shlomai-Fuchs Y*, Shu M, Weissbourd BC, Luo L & Mizrahi A (2013) Dissecting local circuits: parvalbumin interneurons underlie broad feedback control of olfactory bulb output. Neuron 80:1232-45.
Weissbourd B, Ren J, DeLoach KE, Guenthner CJ, Miyamichi K & Luo L (2014) Presynaptic partners of dorsal raphe serotonergic and GABAergic neurons. Neuron 83:645-62; PMID: 25102560.
Schwarz LA*, Miyamichi K*, Gao XJ, Beier KT, Weissbourd B, DeLoach KE, Ren J, Ibanes S, Malenka RC, Kremer EJ & Luo L (2015). Viral-genetic tracing of the input-output organization of a central noradrenaline circuit. Nature 524:88-92.
Beier KT, Steinberg EE, DeLoach KE, Xie S, Miyamichi K, Schwarz L, Gao XJ, Kremer EJ, Malenka RC & Luo L (2015). Circuit architecture of vta dopamine neurons revealed by systematic input-output mapping. Cell 162:622-634.
Wagner MJ, Kim TH, Savall J, Schnitzer MJ & Luo L (2017) Cerebellar granule cells encode the expectation of reward. Nature 544:96-100.
Allen WE*, DeNardo LA*, Chen MZ*, Liu CD, Loh KM, Fenno LE, Ramakrishnan C, Deisseroth K & Luo L (2017) Thirst-associated median preoptic neurons encode an aversive motivational drive. Science 357:1149-1155.
Ren J, Friedmann D, Xiong J, Liu CD, Ferguson B, Weerakkody T, DeLoach K, Ran C, Pun A, Sun Y, Weissbourd B, Neve RL, Huguenard J, Horowitz MA & Luo L (2018) Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems. Cell 175:472-487.
* co-first authors
See publications for complete list and PDFs.