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Updated: Oct 12, 2025
Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals
Published on: October 31, 2011
Aberrant Patterns of Sensory-Evoked Activity in the Olfactory Bulb of LRRK2 Knockout Mice
Andrea Maset1,2, Marco Albanesi1,2, Antonio di Soccio1,2
1Veneto Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.
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.
Insights
Leucine-rich repeat kinase 2 (LRRK2) deficiency impairs olfactory behavior and alters neural network activity in the mouse olfactory bulb. This suggests LRRK2 impacts brain function at a systems level during sensory processing.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- The Leucine-rich repeat kinase 2 (LRRK2) gene is a primary genetic cause of familial Parkinson's disease (PD).
- LRRK2 protein is implicated in presynaptic functions, including vesicle trafficking and neurotransmitter release.
- The system-level impact of LRRK2 on neuronal network dynamics remains largely unexplored.
Purpose of the Study:
- To investigate the role of LRRK2 in neuronal network dynamics at the systems level.
- To determine how LRRK2 deficiency affects brain function, particularly in sensory processing.
Main Methods:
- Utilized a knockout mouse model lacking functional LRRK2 (LRRK2 KO).
- Employed behavioral tests to assess olfactory function.
- Conducted in vivo electrophysiological recordings and functional imaging in the olfactory bulb.
- Analyzed spontaneous and evoked neuronal activity patterns.
Main Results:
- LRRK2 KO mice displayed significant deficits in olfactory-driven behaviors.
- Electrophysiological recordings revealed altered gamma rhythms in LRRK2 KO mice.
- Odorant-evoked neural activity in the olfactory bulb was markedly impaired in the absence of LRRK2.
- Spontaneous neuronal activity showed only minor alterations.
Conclusions:
- LRRK2 plays a critical role in modulating neuronal network activity during active sensory processing.
- The findings highlight the impact of LRRK2 on brain systems-level function, extending beyond its known presynaptic roles.
- This study provides crucial insights into the neurobiological mechanisms underlying LRRK2-associated Parkinson's disease.
