The olfactory circuit is remarkably precise, yet it is plastic. Olfactory sensory neurons in the epithelia, as well as the local neurons in the olfactory bulb, are continuously regenerated and replaced throughout the life of the animal. The connectivity among the neurons in the olfactory bulb undergoes continuous modification during development and in adulthood. However, this plasticity declines with aging and the onset of some neurological diseases such as Alzheimerís and Parkinsonís. We have used mouse genetics to study the plasticity during early development. Currently, we are developing novel transgenic strategies to both manipulate and examine plastic changes in specific neurons.
Precise targeting of the olfactory neurons axons
The olfactory sensory neurons project precisely to their targeted glomeruli during development and throughout the life of the animals. This stereotyped circuit affords the discriminary power of the system. The multiple steps of molecular events are involved in this process and the genetic program is subject to alterations by experience and neural activity. We are examining the genetic program that determines the process.
Activity-Dependent Circuit Formation
We have used genetic methods to manipulate the development of the olfactory map. By selectively dampening neural excitability in the olfactory epithelial neurons during early development, olfactory axons in the transgenic mice show a developmental delay in comparison to axons from wild-type mice. Moreover, the silenced olfactory neurons fail to target to the proper glomeruli in the olfactory bulb such that neurons expressing the same receptor genes innervate multiple glomeruli rather than the two fixed ones seen in the wild-type. This offers the opportunity to investigate the molecular mechanism involved in the development of olfactory circuitry. We are taking several approaches, including deep sequencing and bioinformatic analyses to identify the molecules that are specifically regulated by neural activity.
Stowers Institute | NIH | NIDCD | Kansas City