Prenatal Nicotine Exposure Impairs Executive Control Signals in Medial Prefrontal Cortex

Abstract

Prenatal nicotine exposure (PNE) is linked to numerous psychiatric disorders including attention deficit hyperactivity disorder (ADHD). Current literature suggests that core deficits observed in ADHD reflect abnormal inhibitory control governed by the prefrontal cortex. Yet, it is unclear how neural activity in the medial prefrontal cortex (mPFC) is modulated during tasks that assess response inhibition or if these neural correlates, along with behavior, are affected by PNE. To address this issue, we recorded from single mPFC neurons in control and PNE rats as they performed a stop-signal task. We found that PNE rats were faster for all trial-types, made more premature responses, and were less likely to inhibit behavior on 'STOP' trials during which rats had to inhibit an already initiated response. Activity in mPFC was modulated by response direction and was positively correlated with accuracy and movement time in control but not PNE rats. Although the number of single neurons correlated with response direction was significantly reduced by PNE, neural activity observed on general STOP trials was largely unaffected. However, dramatic behavioral deficits on STOP trials immediately following non-conflicting (GO) trials in the PNE group appear to be mediated by the loss of conflict monitoring signals in mPFC. We conclude that prenatal nicotine exposure makes rats impulsive and disrupts firing of mPFC neurons that carry signals related to response direction and conflict monitoring.

Anterior cingulate cortex is necessary for adaptation of action plans

“…Interestingly, however, at the neural level, firing to the first cue took longer to emerge and was attenuated on sS trials in control rats but not in rats with ACC lesions. Thus, it appears that ACC contributes to the modulation of downstream neural signals after having experienced a trial that required adjustment, either directly, through an intermediate, or in parallel with other structures [e.g., medial prefrontal cortex, orbitofrontal cortex (24,25)]. Consistent with this observation, when ACC was lesioned, firing in DMS during error trials for responses made into the response field was not dampened prior to illumination of the second cue.…”

“…Unilateral electrode implantation procedures were carried out after stereotaxic injection, and electrodes were implanted in the same hemisphere that was targeted by injection. Hemispheres were counterbalanced across groups, and the methods for implantation have been described in detail previously (11,12,24,25,40,41). Rats were chronically implanted with a drivable bundle of 10, 25-μm diameter FeNiCr wires (Stablohm 675, California Fine Wire, Grover Beach, CA) into either the left or right hemisphere of the DMS using the following coordinates relative to bregma (AP: −0.4 mm; ML: ±2.4 mm; DV: −3.5 mm).…”

“…Trials were presented in a pseudorandom sequence such that left and right trials were presented in roughly equal numbers. The time necessary to stop and redirect a motor action (SCRT) on STOP trials was computed using the difference between the average movement time on correct STOP and Go trials (11,12,24,25,40). While we recognize that there are multiple ways to estimate the timing necessary to inhibit a movement (42), we chose to use SCRT because we have access to STOP trial movement time distributions and we varied the STOP-signal delay systematically across sessions, making SSRTmean and integration methods inappropriate for our dataset (1,42).…”

“…Single-Unit Recordings. The procedures for single-unit recordings have been described previously (11,12,24,25,40). Wires were screened daily for activity; if no activity was detected, rats were removed from the testing box and the electrode assembly was advanced 40 to 80 μm.…”

The impact of drugs of abuse on executive function: characterizing long-term changes in neural correlates following chronic drug exposure and withdrawal in rats

“…In rats, we have already used the stop-change task to characterize single unit activity in several brain regions thought to be important for modulating response inhibition (Bryden et al 2012(Bryden et al , 2016(Bryden et al , 2018Bryden and Roesch 2015;Tennyson et al 2018). In our task, rats are required to nose poke and remain in the port for 1000 msec before one of the two directional lights (left or right) is illuminated for 100 msec (Fig.…”