DOI: 10.5061/dryad.9ghx3ffms
title: Cholecystokinin facilitates motor skill learning by modulating neuroplasticity in the motor cortex

description: Cholecystokinin (CCK) is an essential modulator for neuroplasticity in
 sensory and emotional domains. Here, we investigated the role of CCK in
 motor learning using a single pellet reaching task in mice. Mice with a
 knockout of cck gene (CCK-/-) or blockade of CCK-B receptor
 (CCKBR) showed defective motor learning ability; the success rate of
 retrieving reward remained at the baseline level compared to the wildtype
 mice with significantly increased success rate. We observed no long-term
 potentiation (LTP) upon high-frequency stimulation (HFS) in the motor
 cortex of CCK-/- mice, indicating a possible association between
 motor learning deficiency and neuronal plasticity in the motor cortex. In
 vivo calcium imaging demonstrated that the deficiency of CCK signalling
 disrupted the refinement of population neuronal activity in the motor
 cortex during motor skill training. Anatomical tracing revealed
 direct projections from CCK-expressing neurons in the rhinal
 cortex to the motor cortex. Inactivating the CCK neurons in the rhinal
 cortex using chemogenetic methods significantly suppressed motor learning,
 and intraperitoneal application of CCK4, a tetrapeptide CCK
 agonist, rescued the motor learning deficits of CCK-/- mice. In summary,
 our results suggest that CCK, which could be provided from the
 rhinal cortex, enables neuroplasticity in the motor cortex leading to
 motor skill learning.
description: \#Title: Cholecystokinin facilitates motor skill learning by modulating
 neuroplasticity in the motor cortex \[doi:10.5061/dryad.9ghx3ffms] \##For
 all files, we recommend using Excel embedded function or Origin software
 produced by OriginLab Corporation for data import and visulization.
 %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
 Description for each file name: Success rate WT-CKO.xlsx: Success rate of
 WT (wildtype) and CCK-/- (cholecystokinin gene knockout) mice. W
 represents wildtype mice and KO represents CCK (cholecystokinin) gene
 knockout mice. Every single mouse was identified with different serial
 numbers, like W-1, W-2, KO-1,KO-2, and so on (Figure. 1C and Figure
 1-figure supplement 1); WT-CKO hausdorff distance.xlsx: Hausdorff distance
 of trajectories from WT and CCK-/- mice at Day 1 and Day 3. C57 represents
 wildtype mice and CCK-/- represents CCK gene knockout mice. (Figure 1E);
 Detail performance_WT_CKO.xlsx: Detailed performance of WT and CCK-/-
 mice. W represents wildtype mice and KO represents CCK gene knockout mice.
 Every single mouse was identified with different serial numbers, like W-1,
 W-2, KO-1,KO-2, and so on. M, N, D, S represent miss, no-grasp, drop and
 success, respectively (Figure 1G); WT-CKO electrophysiology.xlsx:
 Normalized EPSP of WT mice and CCK knockout mice. WT represents wildtype
 mice and CCK-/- represents CCK gene knockout mice, Ch1, Ch2... represent
 different recording channels (Figure 1H); WT-CKO electrophysiology before
 and after.xlsx: Normalized EPSP of WT and CCK knockout mice before HFS
 (-10-0) and after HFS (50-60) (Figure1I); Basic movement.xlsx: Basic
 movement ability of the CCK-/-. Both CKO and KO represent CCK gene
 knockout mice, WT represents wildtype mice, M1,M2, M3...represent mean
 time or stride-length of different mice (Figure 1- figure supplement
 1C,D,E,F); Success rate Antagonist.xlsx: Success rate of mice injected
 with angtagonist or vehicle. A1, A2, A3,... represent every single mice
 injected with antagonist and V1, V2, V3,... represent every single mice
 injected with vehicle (Figure 2B, Figure 2-figure supplement 1); Detail
 performance_Antagonist.xlsx: Detailed performance of mice injected with
 CCKBR antagonist or vehicle in the motor cortex. A1, A2, A3,... represent
 every single mice injected with antagonist and V1, V2, V3,... represent
 every single mice injected with vehicle (Figure 2C); C57 Calcium
 population activity.xlsx: Population activity of C57BL/6 mice during
 reaching trials at day 1 and day 6. C57-1, C57-2, ... represent every
 single C57BL/6 mouse (Figure 3E and figure 3-figure supplement 1A, B); CKO
 Calcium populational neuronal activity.xlsx: Population activity of CCK-/-
 mice during reaching trials at day 1 and day 6. K1, K2,... represent every
 single CCK gene knockout mouse (Figure 3E and figure 3-figure supplement
 1C, D); L365,260 Calcium populational neuronal activity.xlsx: Population
 activity of C57BL/6 mice injected with antagonist, L365,260, during
 reaching trials at day 1 and day 6. A1, A2, A3,... represent every single
 mouse injected with antagonist (Figure 3E and figure 3-figure supplement
 1E, F); Activated population activity.xlsx: Activated population activity
 of C57BL/6, CCK-/- and C57BL/6 injected with L365,260 (ANT) (Figure 3F);
 Trial-to-trial population activity correlation.xlsx: Trial-to-trial
 population activity correlation of C57BL/6 mice, CCK-/- mice and C57BL/6
 mice injected with L365,260 (Figure 3G); Calcium imaging Hausdorff
 distance.xlsx: Hausdorff distance of trajectories from C57BL/6, CCK-/- and
 C57BL/6 injected with L365,26 at Day 1 and Day 6 (Figure 3H); Success rate
 Chemogentics.xlsx: Success rate of CCK-Cre mice injected with hM4Di virus
 + Clozapine (hM4Di-CLZ), hM4Di virus+saline (hM4Di-saline), Control virus
 + Clozapine (control-CLZ). Serial numbers were used to identify every
 single mouse (Figure 5B, C, figure 5-figure supplement 1); Success rate
 from RC to MC.xlsx: Success rate of C57 mice injected with retro-Cre virus
 in the motor cortex and the hM4Di or control virus in the rhinal cortex,
 and the manipulation after virus expression, including injection with
 saline, Clozapine. mCherry+CLZ represents control virus with clozapine,
 hM4Di+Saline represents hM4Di virus with saline, hM4Di+CLZ represents
 hM4Di virus with clozapine and hM4Di(SMC)+CLZ represents hM4Di injected
 only in the single site of the motor cortex contralateral to the dominant
 forelimb together with clozapine injection (Figure 6D, E, figure 6-figure
 supplement 3A, B, C); Detailed performance \_from RC to MC.xlsx: Detailed
 performance of C57 mice specifically inhbited the projections from the RC
 to the MC and the controls (Figure 6F); Effect of manipulation on learned
 skill.xlsx: Effect of antagonist injection or chemogenetic manipulation on
 the learned motor skill. A-M means miss performance of the antagonist
 injected mouse, A-N means no-grasp performance of the antagonist injected
 mouse, A-D means drop performance of the antagonist injected mouse, A-S
 means success performance of the antagonist injected mouse, C-M means miss
 performance of the hM4Di with clozapine mouse, C-N means no-grasp
 performance of the hM4Di with clozapine mouse, C-D means drop performance
 of the hM4Di with clozapine mouse, C-S means success performance of the
 hM4Di with clozapine mouse. Serial numbers were used to identify different
 single mouse (Figure 2-figure supplement 1D, Figure 6-figure supplement
 3D); CCK4 electrophysiology.xlsx: Normalized EPSP of CCK knockout mice
 administrated with CCK4 or vehicle. Ch-serial nember means different
 recording channels (Figure 7A); CCK4 electrophysiology before and
 after.xlsx: Normalized EPSP of CCK knockout mice administrated with CCK4
 or vehicle before HFS (-10-0) and after HFS (50-60). (Figure 7B); Success
 rate CCK4.xlsx: Success rate of CCK-/-mice injected with CCK4 or vehicle
 (Figuer 7D and Figure 7-figure supplement 1A,B); Detail
 performance_CCK4_Vehicle.xlsx: Detailed performance of CCK-/- mice
 injected (i.p.) with CCK4 or vehicle. V1, V2, V3,... represent every
 single mouse injected with vehicle before training; C1, C2, C3,...
 represent every single mouse injected with CCK4 before training (Figure
 7E);