Aberrant Patterns of Sensory-Evoked Activity in the Olfactory Bulb of LRRK2 Knockout Mice

Abstract

The LRRK2 gene is the major genetic determinant of familiar Parkinson’s disease (PD). Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein involved in several intracellular signaling pathways. A wealth of evidence indicates that LRRK2 is enriched at the presynaptic compartment where it regulates vesicle trafficking and neurotransmitter release. However, whether the role of LRRK2 affects neuronal networks dynamic at systems level remains unknown. Addressing this question is critical to unravel the impact of LRRK2 on brain function. Here, combining behavioral tests, electrophysiological recordings, and functional imaging, we investigated neuronal network dynamics, in vivo, in the olfactory bulb of mice carrying a null mutation in LRRK2 gene (LRRK2 knockout, LRRK2 KO, mice). We found that LRRK2 KO mice exhibit olfactory behavioral deficits. At the circuit level, the lack of LRRK2 expression results in altered gamma rhythms and odorant-evoked activity with significant impairments, while the spontaneous activity exhibited limited alterations. Overall, our data in the olfactory bulb suggest that the multifaced role of LRRK2 has a strong impact at system level when the network is engaged in active sensory processing.

Keywords

• LRRK2
• olfactory alterations
• Parkinson’s disease