Sensory systems must be plastic in order to allow learning throughout the lifespan; however, brain regions involved in processing sensory information undergo a significant decline in plasticity during both normal aging and in concert with neuropsychiatric and neurodegenerative diseases. For example, olfactory deficits are estimated to affect more than half of the elderly population in the United States. One promising feature of the olfactory system, however, is its extensive capability for lifelong plasticity. In rodents, the olfactory bulb (OB) is one of the most plastic areas of the adult brain due to ongoing neurogenesis. Adult-born granule cells (abGCs) are the most numerous population of adult-born neurons, and during their maturation, they develop synapses with existing cells and integrate into the OB circuit. However, there is still limited information about the development of abGCs? responses to stimuli in vivo. This project aims to use longitudinal in vivo multiphoton calcium imaging of individual abGCs? odor-evoked responses to characterize (1) when abGCs first become responsive to olfactory stimuli and how the responses of individual neurons change over time as the cells mature and (2) how this process may be modified in the context of olfactory learning. Preliminary data indicates that on a population level, abGCs are more responsive to odors early during their development. This supports the hypothesis that abGCs? initially broad representations may be refined to enhance their selectivity for particular odors as they mature. Analyzing the odor response profiles of identified cells over time will allow the investigation of the timecourse of an individual cell?s odor response magnitude, stability and odor selectivity on a single cell level. In addition, training mice in an operant behavioral task during the critical period of a cohort of abGCs will provide insight into the effects of odor exposure and odor-reward associations on the stability and prevalence of abGC responses. Together, these experiments will provide important insights into the process by which adult-born neurons integrate into an existing circuit and possible mechanisms by which this process may be modified by learning in order to enhance sensory processing.
Over half of adults over age 65 have major olfactory impairment, and a decline in olfactory abilities is a potential marker for neuropsychiatric and neurodegenerative diseases. Therefore, it is essential that we investigate the olfactory system?s potential for plasticity and regeneration. This project seeks a better understanding of ongoing neurogenesis in the olfactory bulb, which can provide the foundation for future efforts to enhance plasticity and regeneration in the olfactory system and other brain regions.
|Wallace, Jenelle L; Wienisch, Martin; Murthy, Venkatesh N (2017) Development and Refinement of Functional Properties of Adult-Born Neurons. Neuron 96:883-896.e7|