Dopaminergic Periglomerular Cells Regulate Olfactory Output In Mice Through Inhibiting External Tufted Cells

Objective: In the central nervous system,dopamine is one of the most important neurotransmitters regulating different physiological functions,such as cognition process and motor activity.Early clinical studies of Parkinson's patients have shown that the level of dopamine is also related to olfactory function.It is significant to understand the role of dopamine in olfactory information processing,which will contribute to the pathogenesis and early diagnosis of neurodegenerative diseases.The main purpose of this research is to explore the role of dopaminergic periglomerular cells in regulating olfactory neural circuits and olfactory function.Methods: The distribution of dopaminergic periglomerular cells in the olfactory bulb was observed by immunofluorescence staining.ChR2-mCherry recombinant adenovirus was stereotacticly injected into the glomerular layer of the transgenic mouse brain.After two to three weeks,300?m acute brain slices of the olfactory bulb were prepared for patch clamp recordings.The responses of different cells were observed under 488 nm laser stimulation.The recombinant adenovirus was injected into the glomerular layer of the transgenic mouse brain to express hM3 Dq specifically in dopaminergic periglomerular cells.The activity of dopaminergic cells can be enhanced by intraperitoneal injection of CNO.The recombinant adenovirus was also used to express DTR in dopaminergic periglomerular cells.Dopaminergic periglomerular cells can be damaged by intraperitoneal injection of DT.The olfactory behaviors were compared between control and CNO/DT injection animals.Results: TH and GAD67 were co-expressed in dopaminergic periglomerular cells.The dopaminergic periglomerular cells expressing ChR2-mCherry can be activated under blue light stimulation.Obvious outward current and depolarization can be observed in external tufted cells after activation of dopaminergic periglomerular cells.The outward current can be completely blocked by GABA receptor antagonists.Conclusion: Dopaminergic periglomerular cells co-release dopamine and GABA.Dopaminergic periglomerular cells form inhibitory synapses with external tufted cells.Dopaminergic periglomerular cells inhibit external tufted cells by releasing GABA to modulate the information output of the olfactory bulb.Dopaminergic periglomerular cells play an important role in regulating signal processing in the olfactory bulb,and therefore may affect the olfactory detection sensitivity in animals.