Fig. 1: Experimental and behavioral set up for investigating the effect of direct ventral tegmental area (VTA) dopaminergic projections to M1 on motor learning.
a Schematic of the viral injection of the genetically encoded GCaMP6s to M1 and inhibitory (hM4D) DREADDs to the VTA. CNO was applied locally to M1 via an access port in the relevant experiments. b Behavioral setup. Mice were head-fixed and trained to grab a food pellet positioned on a rotating table. Trial structure (12 sec); tone (go signal) after 4 sec, plate rotates, and pellet reaches position at tone+0.4 sec. c Example of a typical field of view showing average projections of two-photon imaging of GCaMP6-positive layer 2-3 neurons (250 µm from pia) of an M1 field. d Left panel: A coronal section showing staining of hM4D DREADDs with mCherry (red) in the VTA. White dashed lines label the VTA and other surrounding nuclei based on the Paxinos and Franklin’s mouse brain atlas. White rectangle encloses the VTA and is magnified and shown in the right panel. Histology was validated for all manipulated mice. e Experimental design for learning a motor task for the control and manipulated mice groups during VTA inhibiting with local CNO in M1. Shaded points in the blue box indicate the manipulated session. f Population and average data (mean ± SEM) of success rate (fraction of successful trials) per training session during learning, n = 12 for controls and n = 10 for manipulated mice (p = 3.6·10−8 unpaired two-tailed t-test comparing success rate in the 3rd session of manipulated group n = 10 mice to control group, n = 12). Shaded data in the blue box indicate the manipulated session. g Success rate (mean ± SEM) of four groups: the Ringer group and sham group (n = 4 and n = 3 mice respectively) compared with success rate of the two main groups (control and manipulated, n = 12 and n = 10 mice respectively, same as in f). h Success rate (mean ± SEM) of four groups: the substantia nigra pars compacta (SNc) group and primary visual cortex (V1) group (n = 3 mice each) compared with the two main groups (control and manipulated, n = 12 and n = 10 mice respectively, same groups as in f). i Success rate of expert animals (n = 8, left bar) compared with an additional session where CNO was injected locally to M1 (expert+CNO, right bar) (mean ± SEM). Source data are provided as a Source Data file. Illustrations 1a, e credit to Dafna Antes. Figure 1b, e are adapted from Yara Otor et al., Dynamic compartmental computations in tuft dendrites of layer 5 neurons during motor behavior.Science376,267-275(2022).DOI:10.1126/science.abn1421 with permission.
