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| Poster #406 Don Tucker Finalist: Genetically-heterogeneous Orexin-A Inputs to the Mouse Olfactory Bulb Modulate Mitral/Tufted Cells via Orexin Receptor Type 1 and 2 |
| Meizhu Qi1,2, Debra Fadool1,2,3, Douglas Storace1,2,3 1Department of Biological Science, Tallahassee, FL, United States 2Program in Neuroscience, Tallahassee, FL, United States 3Institute of Molecular Biophysics, Tallahassee, FL, United States |
The olfactory bulb (OB) receives direct projections from the lateral hypothalamus that includes a population of neurons expressing the neuropeptide orexin-A. These neurons are genetically heterogeneous, with distinct subsets that co-express vesicular glutamate transporters (VGLUT1 or VGLUT2). Herein, we used a combination of virally-mediated anterograde tract tracing and immunohistochemistry to map orexin-A inputs in the OB with high-resolution confocal microscopy and used slice electrophysiology to better understand the functional role of orexin-A inputs. Orexin-A expression was broadly distributed throughout the OB, with similar expression density in different anatomical layers and across the anterior-posterior axis. Morphological analysis of orexin-A axon terminals revealed that 67% co-expressed VGLUT2. The remainder either co-expressed VGLUT1 or lacked glutamatergic markers. A total of 111 mitral/tufted cells (M/TCs) were current-clamped in the whole-cell configuration, whereby evoked currents were elicited in the presence of synaptic blockers. Bath application of 100 nM orexin-A modulated action potential (AP) firing frequency in 79% of M/TCs, with 49% inhibited (decrease AP firing frequency 0.51) and 51% excited (increase AP firing frequency 0.85). The orexin-R type I antagonist (SB-334867-A) changed the AP firing frequency compared with orexin-A alone in 9 of 15 cells, whereas the orexin-R type 2 antagonist (TCS-OX2-29) affected AP firing frequency in 7 of 10 cells. This suggests that both type I and 2 receptors contribute to orexin A modulation of M/TCs. The results highlight the genetic heterogeneity of orexin-A inputs to the OB and provide new insights into the complex mechanisms underlying orexin-A modulation of olfactory sensory processing. |