Figure 1.

Experimental design. A, Cartoon illustrating the skilled reaching lever-press task paired with optogenetic stimulation of the LC. B, Example rewarded (hit, red) and unrewarded (miss, gray) trial from a single session. Rats were required to press the lever past the “Hit Threshold” (9.5° below horizontal) and return it to less than 4.75° from horizontal (“Release Threshold”) within a 2 s time window to receive a food reward. Unrewarded miss trials were those in which rats either failed to reach the hit threshold or failed to release the lever within the required time window. C, Experimental timeline. Male and female Long–Evans TH-Cre + rats began training on the lever-press task prior to the surgical infusion of eYFP-tagged Cre-dependent virus and the implantation of an optical fiber over the left LC. After surgery, rats were trained until behavioral criteria were reached and then dynamically allocated to a treatment group. During LC Stim treatment, rats received five training sessions in which 3, 10, or 30 Hz LC stimulation was paired with each correct lever press. Cortical motor mapping was performed within 24 h of the last training-paired stimulation session. D, Optogenetic stimulation consisted of a 0.5 s train of 470 nm laser pulses delivered at 3, 10, or 30 Hz. E, 4× (top) and 20× (bottom) images from one subject showing virus expression and the placement of the optical fiber in the left LC. Slices were stained for GFP (ChR2-eYFP, green) and tyrosine hydroxylase (TH, yellow). F,G, Total training sessions performed (F) and age at ICMS mapping (G) were balanced across treatment groups.