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. 2022 Mar 14;32(5):1163–1174.e6. doi: 10.1016/j.cub.2021.12.027

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© 2022 The Authors

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMC Copyright notice

Optogenetic stimulation of DMS dopamine during seeking accelerates habit formation

(A) AAV injection into substantia-nigra pars-compacta (SNpc) of Th::Cre rats induced ChR2-EYFP or EYFP (control) expression in dopamine neurons. DMS dopamine terminals were optogenetically stimulated bilaterally.

(B) Immunostaining for tyrosine hydroxylase (TH) and EYFP indicates selective virus expression in midbrain dopamine neurons (bottom) and their striatal terminals (top). SNR, substantia nigra pars reticulata; VTA, ventral tegmental area.

(C) Percentage of time spent in the DMS-photo-stimulated (active) quadrant of an open-field arena. No significant difference (ns) was observed between ChR2 and EYFP rats.

(D) Nose pokes into the active port triggered DMS dopamine photo stimulation. We observed no significant differences (ns) within or between ChR2 and EYFP animals in the number of active and inactive nose pokes.

(E) During seeking-taking training, seeking presses triggered DMS dopamine photo stimulation. The conditioning “logic” translated from training to preference test: food-magazine head entries were executed more frequently after taking-lever presses than after seeking-lever presses, both in habitual and non-habitual rats. Histogrammed data with mean ± SEM shown separately.

(F) No significant differences were found in frequency of food-magazine head entries outside VI60, when no levers were extended.

(G) ChR2 animals made more distal VI60 seeking-lever presses (left). No significant difference was found for food-magazine head entries during VI60 (right).

(H) Similarly, no group differences were observed for the head-entry probability during the 3-s period following seeking-lever retraction and prior to taking-lever extension (right).

(I) In week 1, both ChR2 and EYFP rats preferentially pressed the taking lever during the habit test. By week 3, this preference had shifted to the seeking lever for the ChR2 rats, but not the EYFP rats.

(J) The ChR2 group made significantly more seeking-lever responses, but groups did not differ in taking-lever presses. Data in (E) and (F) are mean ± SEM. ^∗p < 0.05, ^∗∗p < 0.01.