Cannabinoids modulate associative cerebellar learning via alterations in behavioral state
- Champalimaud Neuroscience Program, Champalimaud Center for the Unknown, Portugal
Figures
Figure 1 with 2 supplements
Correcting for differences in locomotor activity accounts for apparent deficits in eyeblink conditioning.
(A) Setup for eyeblink conditioning in head-fixed mice on a running wheel, showing an LED as the CS and an air-puff US. (B) Sagittal sections showing the complete elimination of CB1R (red) in CB1KOs …
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Figure 1—source data 1
Source data for Figure 1 and related supplements.
- https://cdn.elifesciences.org/articles/61821/elife-61821-fig1-data1-v1.mat
Figure 1—figure supplement 1
Various measures of altered behavioral state in CB1KO mice and relationship to learning.
(A) Average distance run on the treadmill in each training session for each (genotype, superimposed). (B – E) Global CB1 knockout animals (red, N = 11) walk overall more slowly than littermate …
Figure 1—figure supplement 2
Learned response timing and short-term, single-trial learning are normal in global CB1KO mice.
(A) Average conditioned responses (CR) for CB1KO (red, N = 8) and littermate controls (black, N = 8) trained to a 500 ms CS-US interstimulus interval. Data are from CS-only trials from two test …
Figure 2 with 2 supplements
Equalizing locomotor activity with a motorized treadmill rescues CB1-related learning deficits.
(A) Average %CR learning curves of global CB1 knockout (red, N = 6) mice and littermate controls (black, N = 6), while running at a fixed speed (0.12 m/s) on a motorized treadmill. Error bars …
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Figure 2—source data 1
Source data for Figure 2 and related supplements.
- https://cdn.elifesciences.org/articles/61821/elife-61821-fig2-data1-v1.mat
Figure 2—figure supplement 1
CB1R antagonist AM251 causes hypoactivity, both across groups and within animals.
(A – D) Animals were injected with AM251 (N = 9) or with vehicle (N = 9) and different parameters were measured 30 min post-injection, while the animals were head-fixed, but could walk on the …
Figure 2—figure supplement 2
Vehicle (DMSO) solution drives hypoactivity in mice, preventing them from learning on the self-paced treadmill.
(A) Average %CR learning curves of mice injected with AM251 (N = 9) or with vehicle (N = 9) 30 min before each training session on the self-paced treadmill, for a total of 10 sessions. Thin lines …
Figure 3 with 1 supplement
Eyeblink conditioning is intact in granule-cell-specific CB1 knockout mice.
(A) Sagittal sections showing the selective elimination of CB1R (red) from cerebellar granule cells in G6KO and DAPI staining the granule-cell layer (blue). Images of the cerebellum of a …
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Figure 3—source data 1
Source data for Figure 3 and related supplements.
- https://cdn.elifesciences.org/articles/61821/elife-61821-fig3-data1-v1.mat
Figure 3—figure supplement 1
Several measures of behavioral state reveal no differences between granule-cell-specific CB1 knockout mice and controls.
Granule-cell-specific CB1 knockout mice (blue, N = 9) and their littermate controls (cyan, N = 9), show similar levels of average walking speed (A, p=0.70), percent time walking (B, p=0.79), …
Figure 4 with 3 supplements
Locomotor learning in global and granule-cell-specific CB1 knockout mice.
(A) Experimental protocol for split-belt locomotor adaptation. Mice underwent adaptation protocols consisting of baseline, split-belt (adaptation) and washout phases. Belt speeds were equal (‘tied’) …
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Figure 4—source data 1
Source data for Figure 4 and related supplements.
- https://cdn.elifesciences.org/articles/61821/elife-61821-fig4-data1-v1.mat
Figure 4—figure supplement 1
Analysis of overground locomotion in global and granule-cell-specific CB1KO mice.
(A) Mean (+/- SEM) individual limb parameters stride length (left), cadence (middle) and stance duration as a function of walking speed for global CB1KO mice (N = 7) and their littermate controls (N …
Figure 4—figure supplement 2
Linear discriminant analysis separates CB1KO mice from two mutants with cerebellar ataxia.
(A) Linear discriminant analysis (LDA) of locomotor parameters separates mutants with cerebellar ataxia (pcd and reeler) from global and cell-specific CB1KO and size-matched controls. For this …
Figure 4—figure supplement 3
Analysis of treadmill locomotion in global and granule-cell-specific CB1KO mice.
(A) Mean (+/- SEM) individual limb parameters stride length (left), cadence (middle) and stance duration as a function of walking speed for global CB1KOs (N = 12; red) and their littermate controls …
Videos
Video 1
Example movie of littermate control mouse (top) and global CB1KO mouse (bottom) walking on LocoMouse overground setup.
Video 2
