Presentation Details
| The role of evoked activity in the survival and functional integration of newborn olfactory sensory neurons Kendall A Curtis, Sarah PR Berg, Claire EJ Cheetham. University of Pittsburgh, Pittburgh, PA, USA |
Abstract
Stem cells are a potential therapeutic intervention for olfactory sensory loss in a range of conditions such as Parkinson’s disease and COVID-19-related anosmia, as well as for brain regeneration in other neurological and neurodegenerative diseases. Understanding the mechanisms by which endogenous stem-cell-derived neurons integrate into circuits is integral to effective clinical translation. Olfactory sensory neurons (OSNs) are generated throughout life in humans and mice—unlike most other mammalian neurons—providing a unique opportunity to understand the mechanisms by which these endogenous stem-cell-derived neurons integrate into highly ordered olfactory bulb (OB) circuits. However, we have found that newborn OSNs have a low 14-day survival rate. It is unknown what factors determine immature OSN survival and functional integration into the OB. We have shown previously that immature OSNs provide odor input to the OB. Thus, the immature phase of OSN development may represent a key time window during which survival and functional integration are determined. We hypothesize that evoked activity of immature adult-born OSNs promotes their survival and functional integration into OB circuits. When analyzing activity in the olfactory epithelium, we found that survival of newborn OSNs was significantly higher in odor-exposed mice compared to controls (p=0.006), suggesting that evoked activity promotes newborn OSN survival. We are currently determining the effect of altered evoked activity on functional integration of immature OSNs using in vivo optogenetic stimulation of immature OSNs and 2-photon calcium imaging of mitral and tufted cells. Understanding the factors that impact immature OSN survival and functional integration into OB circuits is fundamental to our understanding of olfactory plasticity.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.