Neuronal correlates of post-error slowing in the rat dorsomedial prefrontal cortex

Abstract

Rats with impaired function in dorsomedial regions of the prefrontal cortex (dmPFC) are unable to maintain a behavioral response over a delay period. Here we report that neurons in this cortical region are prominently modulated after errors in a tone-cued, simple reaction time task and that inactivation of dmPFC attenuates a slowing of reaction times that is observed following errors. Using methods for chronic single-unit recording, we found that approximately one-third of dmPFC neurons were modulated after errors, and 28% of these neurons had increased posterror firing that persisted into the delay period of the following trial. In contrast to dmPFC, no such neurons were found in motor cortex. Our results implicate the dorsomedial prefrontal cortex in a form of retrospective working memory that improves task performance following errors.

FIG. 1.

Behavioral task and electrode locations: Animals had to press and hold a lever for a 1.0-s delay period and release the lever promptly (i.e., within 0.6 s) to receive a liquid reward. The end of the delay period was signified by a 72-dB 8-kHz tone; in some recording sessions, the tone was omitted on 50% of trials. If animals released the lever prior to the end of the 1.0-s delay or after the 0.6-s response window, then these trials were scored as errors (premature or late, respectively), and all behavioral devices (pump, lever and houselight) were extinguished for 4–8 s. B: electrode locations: Recording sites in dorsomedial prefrontal cortex (dmPFC) are shown from 8 animals that were implanted with microwire electrodes arrays in dmPFC (white dots) and from 7 animals that were implanted with microwire electrode arrays in motor cortex (black dots) and cannula in dmPFC (black crosses). Reconstructions are shown in frontal planes based on atlas sections (Paxinos and Watson 1982).

FIG. 2.

Posterror slowing of reaction times (RTs). A: RTs following correct trials (black line) decreased over learning but were consistently faster than RTs following error trials (gray line) only after the 16th day of training. Asterisk indicates significant posterror slowing (P < 0.05). B: learning of the simple RT task. Animals increased their correct responses (black line) over the course of several days, reaching 60% on the 11th day of training. Premature errors (dark gray line) decreased over training [paired T_(1,6) = 10.2, P < 0.001 on day 1 vs. 11], and late errors (light gray line) decreased somewhat [paired T_(1,6) = 2.00, P < 0.09 on day 1 vs. 11]. C: posterror slowing in control sessions was attenuated in sessions with dmPFC inactivated, as RTs became equivalent following errors and correct trials. Asterisk indicates significant posterror slowing (P < 0.05).

FIG. 3.

Errors influence persistent activity of dmPFC neurons. A: sequence of events following correct and error trials. Following correct trials (top line, black), a pump is activated at a latency of 100 ms after lever release and is kept on for 1 s. Following error trials (bottom line, gray) the house lights and all behavioral devices are extinguished for 4–8 s. Houselights then come on 1.5 ± 0.2 s prior to posterror lever presses. B–E: examples of neurons that fired differently depending on trial outcome are shown. B and C: neurons fired more if trials ended in error (gray colors, left panel) than if trials were correct and rewarded (black, left panel). Increased posterror firing (gray colors, right panel) persisted into the delay period of the following trial, and for these neurons, was more than postcorrect firing (black, right panel). Shaded region after lever press on right panel was used to identify delay-related posterror differences in firing rate. No difference was observed between premature (dark gray) and late (light gray) errors; see text.

FIG. 4.

Posterror modulation indices. Posterror (gray) or postcorrect (black) delay-related modulation indices plotted for dmPFC (A) and for motor cortex (B). Although dmPFC neurons could have greater firing rate following errors and correct trials, dmPFC had significantly more neurons with posterror delay activity than motor cortex, while motor cortex had significantly more neurons with postcorrect delay activity than dmPFC.