GABAA receptor agonist muscimol rescues inhibitory microcircuit defects in the olfactory bulb and improves olfactory function in APP/PS1 transgenic mice

Author(s):  
Bin Hu ◽  
Chi Geng ◽  
Feng Guo ◽  
Ying Liu ◽  
Yu-Chen Zong ◽  
...  
2009 ◽  
Vol 23 (3) ◽  
pp. 239-243 ◽  
Author(s):  
Sayaka Yagi ◽  
Richard M. Costanzo

Background Impaired olfactory function leads to a decrease in the quality of life for many patients. Surgical treatment options are limited, especially for those suffering from hyposmia or anosmia after posttraumatic injury to the olfactory nerves. Stem cells located in the olfactory epithelium (OE) have the capacity to grow new neurons, making the OE an ideal candidate for restorative tissue grafting. This study was performed to determine if strips of OE survive transplantation directly to the olfactory bulb (OB). Methods Transgenic mice, expressing a green fluorescent protein (GFP), were used to obtain the donor graft tissue. Strips of OE from GFP donor mice were transplanted directly to sites in the OB and cerebral cortex (CC; control sites) of wild-type mice. Graft survival rates at 30 days were determined for transplant sites in the OB and CC. Results Strips of OE from transgenic mice survived transplantation to the OB and continued to express the GFP marker protein. The 30-day survival rate in the OB (83%, 5 of 6 grafts) was the same as in the CC (10 of 12 grafts). The morphology of the graft revealed characteristics found in normal OE. Conclusion We showed that strips of OE can be successfully grafted to both the OB and CC. Grafts of the OE, if strategically positioned on the ventral surface of the bulb and given access to the nasal cavity, could provide the basis for new surgical treatments to restore olfactory function.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Benjamin Roland ◽  
Rebecca Jordan ◽  
Dara L Sosulski ◽  
Assunta Diodato ◽  
Izumi Fukunaga ◽  
...  

Perturbations in neural circuits can provide mechanistic understanding of the neural correlates of behavior. In M71 transgenic mice with a “monoclonal nose”, glomerular input patterns in the olfactory bulb are massively perturbed and olfactory behaviors are altered. To gain insights into how olfactory circuits can process such degraded inputs we characterized odor-evoked responses of olfactory bulb mitral cells and interneurons. Surprisingly, calcium imaging experiments reveal that mitral cell responses in M71 transgenic mice are largely normal, highlighting a remarkable capacity of olfactory circuits to normalize sensory input. In vivo whole cell recordings suggest that feedforward inhibition from olfactory bulb periglomerular cells can mediate this signal normalization. Together, our results identify inhibitory circuits in the olfactory bulb as a mechanistic basis for many of the behavioral phenotypes of mice with a “monoclonal nose” and highlight how substantially degraded odor input can be transformed to yield meaningful olfactory bulb output.


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