Abstract:
The olfactory bulb (OB) is responsible for processing odor information and shows experience-based plasticity. OB houses various types of neurons, including tyrosine hydroxylase (TH)-expressing dopaminergic neurons found within the glomerular layer (GL). The expression of TH dopaminergic interneurons in OB has a vital role in odor information processing. Previous studies have focused on the role of TH under odor- enriched conditions, as changes in its expression can occur in an odor-experience- dependent manner, but whether these changes are odor-specific is not known. We systematically address this using odor exposure and odor discrimination paradigms in M72-GFP mice to determine the regulation and selection of TH expression due to the valence of associated odors and the duration of odor exposure. Using acetophenone, which is an odor investigated to activate the M72 glomerulus, we observe that chronic but not acute exposure to the odor acetophenone leads to an approximately 66% increase in association paradigm where the total exposure to acetophenone matches acute exposure conditions to test the valence-dependent plasticity of TH cells. Reward association leads to a notable 40% increase in TH expression surrounding the M72 glomerulus, but not when the same odor is behaviorally irrelevant. This suggests that a valence-dependent increase can occur even with low-odor exposure. OB receives cholinergic feedback from the diagonal band nucleus that dishabituates sensory responses. To test if cholinergic- mediated dishabituation of odors is vital for TH expression, we use a DREADD-based neural activation approach in our passive exposure paradigms. Accordingly, using AAV- hSyn-DIO-DREADD(Gq) viral vectors in Chat-Cre; R26R-tdT; M72-GFP mice, we observed a 60% increase in TH cell populations in the acute exposure condition with administration of CNO intraperitoneally compared to acute exposure without the CNO injection. This highlights the role of top-down odor dishabituation in modulating TH expression. Overall, our results demonstrate that the odor exposure conditions, along with their relevance to goal-directed behaviors, play a crucial role in regulating dopaminergic cells in OB. These findings are vital for optimizing olfactory bulb circuit adaptation and enhancing animal’s ability to recognize relevant odors in their natural environment.
