Automatic Analysis of the Frequency, Vigor, and Complexity of Spontaneous Locomotion Bouts of Mice with Loss and Gain of Function of the G Protein-Coupled Receptor Smoothened in Cholinergic Neurons

Author

Aleksandra Feshchenko, The Graduate Center, City University of New YorkFollow

Date of Degree

9-2023

Document Type

Thesis

Degree Name

M.S.

Program

Cognitive Neuroscience

Advisor

Andreas Kottmann

Subject Categories

Behavioral Neurobiology | Cognitive Neuroscience | Other Neuroscience and Neurobiology

Keywords

GPCR Smoothened, Cholinergic Interneurons, Striatum, Locomotion

Abstract

Locomotion, a fundamental behavior, is classically assessed using simple metrics of velocity and total distance moved in an open field. This behavior however offers rich data about the organization and breadth of actions an animal can take while only facing limitations due to the bio-mechanical constraints of the organism. Importantly, these actions are not biased towards a particular task-solution space imposed by many behavioral paradigms. Here, to analyze motor complexity in freely ambulating mice, we developed a method for the automatic and unbiased identification of locomotor bouts which we call Bout Finder (BF). This analysis utilizes Open Feld data to derive and quantify 24 locomotion parameters. To test BF sensitivity, we compared it against previously established methods. BF was then applied to examine locomotor differences between mice with selective gain and loss of G protein-coupled receptor (GPCR) Smoothened (Smo) function in cholinergic interneurons (CIN). CIN are the main source of striatal Acetylcholine and are critical for action switching. Our group also previously demonstrated that the activation or ablation of Smo can impinge on CIN physiology. Basic Open Field analysis showed that mice with constitutively active Smo signaling selectively on CIN (SmoM2C/-:ChATCre) moved less overall and at reduced average speeds compared to controls. However, BF analysis revealed that the nature of these differences was due to reduced number and duration of locomotor bouts longer than 0.5s among SmoM2C/-:ChATCre v animals versus controls. Within these bouts, mean velocity, maximal velocity, distance traveled, average acceleration, maximal acceleration, and average number of acceleration inversions were all reduced while time to max velocity was increased. These differences were not observed among bouts shorter than 0.5s. The overall differences in locomotion observed between control and SmoM2C/-:ChATCre mice is therefore due to a deficit reaching higher velocities and initiating locomotor bouts among SmoM2C/-:ChATCre animals. In contrast, ablation of Smo selectively from CINs produced no difference in gross distance moved and mean velocity compared to controls. However, application of BF revealed a significant difference in time to maximal speed within bouts longer than 0.5s. Specifically, CIN-specific Smo ablation animals showed reduced average time to maximal velocity within bouts suggesting a that the differences of this group from the controls also present. Together, these results not only validate our novel bout detection method for the analysis of rich naturalistic locomotion, but also reveal bidirectional changes in locomotor complexity following manipulations to Smo on CINs

Recommended Citation

Feshchenko, Aleksandra, "Automatic Analysis of the Frequency, Vigor, and Complexity of Spontaneous Locomotion Bouts of Mice with Loss and Gain of Function of the G Protein-Coupled Receptor Smoothened in Cholinergic Neurons" (2023). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/5553