The olfactory bulb is the first olfactory circuit where information doesn't make sense. This circuit takes genetically ordered inputs and scrambles them into outputs that, despite decades of research, have not been decoded. Olfactory bulb output is greatly shaped by interactions between granule cell interneurons and mitral/tufted cell principal neurons. Granule cell interneurons are particularly interesting because they are continuously replaced during adulthood and because their connectivity indicates that they integrate disparate inputs from higher brain regions. However, it is unclear how these unique features impact circuit function.
This thesis examines the function of granule cells by manipulating their adult neurogenesis and by probing circuit function after genetic manipulation. We present five general findings. 1) The structure and the function of the granule cell layer is resistant to changes in the magnitude of adult neurogenesis. 2) Animals with reduced adult neurogenesis have behavioral disruptions to a larger system that includes cortical and limbic regions in the association between odors and fear. By probing the synapse between granule and mitral cells we found that: 3) the granule-mitral cell circuit functions with spatial homogeneity indicating distributed synaptic connectivity. 4) Granule cells are modulated by the breathing rate of the animal, and disruptions to this modulation in prion protein knockout mice are associated with the inability to make olfactory discriminations. Finally: 5) evidence from AC3-/- anosmic mice suggests that centrifugal inputs impose a centrally generated breathing rhythm onto granule cells. These results generally support a model where granule cells function by focusing temporal patterns of centrifugal input onto distributed ensembles of mitral cells.
|Advisor:||Firestein, Stuart J.|
|School Location:||United States -- New York|
|Source:||DAI-B 72/05, Dissertation Abstracts International|
|Keywords:||Granule cells, Interneurons, Local field potentials, Neurogenesis, Olfactory bulb|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be