In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odor map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-transsynaptic tracing with genetics to control the location, number and type of ‘starter’ cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive direct convergent input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odor preference or associative memory. This transsynaptic tracing method should be widely applicable to mapping connections throughout the mouse nervous system. Future improvements of the system will be discussed. These include 1) a potential anterograde trans-neuronal tracer; 2) genetic modification of starter cells to combine circuit tracing with genetic loss- or gain-of-function experiments; 3) a novel strategy to select starter cells of tracing based on their receptive fields. These approaches will facilitate the investigation of not only connection diagrams, but also molecular basis and functional organization of neuronal connections within neural circuits.

Reference:
Miyamichi K, Amat F, Moussavi F, Wang C, Wickersham I, Wall NR, Taniguchi H, Tasic B, Huang ZJ, He Z, Callaway EM, Horowitz MA, Luo L. Cortical representations of olfactory input by trans-synaptic tracing. Nature 472, 191-196, 2011