Abstract
The primary motor cortex (M1) is known to be a critical site for movement initiation and motor learning. Surprisingly, it has also been shown to possess reward-related activity, presumably to facilitate reward-based learning of new movements. However, whether reward-related signals are represented among different cell types in M1, and whether their response properties change after cue-reward conditioning remains unclear. Here, we performed longitudinal in vivo two-photon Ca2+ imaging to monitor the activity of different neuronal cell types in M1 while mice engaged in a classical conditioning task. Our results demonstrate that most of the major neuronal cell types in M1 showed robust but differential responses to both the conditioned cue stimulus (CS) and reward, and their response properties undergo cell-type-specific modifications after associative learning. PV-INs' responses became more reliable to the CS, while VIP-INs' responses became more reliable to reward. Pyramidal neurons only showed robust responses to novel reward, and they habituated to it after associative learning. Lastly, SOM-INs' responses emerged and became more reliable to both the CS and reward after conditioning. These observations suggest that cue- and reward-related signals are preferentially represented among different neuronal cell types in M1, and the distinct modifications they undergo during associative learning could be essential in triggering different aspects of local circuit reorganization in M1 during reward-based motor skill learning.
Highlights
The primary motor cortex (M1) is an essential site for movement execution and motor learning
When we compared the mean percent of cue stimulus (CS)-responsive neurons on day 1 and day 7, we found that the average percent of CS-responsive PV-INs during a trial increased significantly by day 7, while the percent of CS-responsive VIP-INs did not change, demonstrating that more PVINs became responsive to the CS after associative learning
M1 is known to be involved in motor initiation, movement kinematics and motor learning
Summary
The primary motor cortex (M1) is an essential site for movement execution and motor learning. To understand how reward-associated signals are represented within the local microcircuitry in M1 before and after associative learning, we established a head-fixed auditory cued reward conditioning task, which allowed us to combine the task with in vivo two-photon Ca2+ imaging to examine the response properties of different neuronal cell type populations in awake and behaving mice (Figure 1A). Since M1 is known to be involved in movement initiation and motor skill learning, we chose to use a simple classical conditioning task with just an auditory tone paired with reward and omitted any additional training where mice would be required to learn a new movement The rationale for this is that many neuronal cell types, including PNs, PV- and SOM-INs, have been shown to undergo modifications when mice acquire new movements (Chen et al, 2015; Cichon & Gan, 2015; Donato et al, 2013; Xu et al, 2009). After 3-5 weeks, we recorded the activity of hundreds of L2/3 PNs using two-photon microscopy in awake mice while they underwent the head-fixed conditioning task, and we tracked the same population of neurons on day 1 and day 7
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