A genetic approach to trace neural circuits

Mammalian nervous system function involves billions of neurons which are in terconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactory-specific promoter, H-e selectively expressed barley lectin In sensory neurons in the olfactor y epithelium and vomeronasal organ of transgenic mice. The lectin was trans ported through the axons of those neurons to the olfactory bulb, transferre d to the bulb neurons with which they synapse. and transported through the axons of bulb neurons to the olfactory cortex, The lectin also was retrogra dely transported from the bulb to neuromodulatory brain areas,;No evidence could be obtained for adverse effects of the lectin on odorant receptor gen e expression, sensory axon targeting in the bulb, or the generation or tran smission of signals by olfactory sensory neurons. Transneuronal transfer wa s detected prenatally in the odor-sensing pathway, but only postnatally in the pheromone-sensing pathway, suggesting that odors, but not pheromones, m ay be sensed in utero, Our studies demonstrate that a plant lectin can serv e as a transneuronal tracer when its expression is genetically targeted to a subset of neurons. This technology can potentially be applied to a variet y of vertebrate and invertebrate neural systems and may be particularly val uable for mapping connections formed by small subsets of neurons and for st udying the development of connectivity as it occurs in utero.