Neuromodulation of inhibitory control and the effects of chronic stress
The ability to withhold a response is a core component of executive function, and it is compromised across a wide range of neuropsychiatric conditions. The prefrontal cortex relies on converging neuromodulatory input to support this function, and chronic stress readily degrades it. We use optical recording of neuromodulator dynamics, cell-type-and projection-specific manipulation, and rodent behavioral paradigms that require action suppression to ask how neuromodulatory signals in the prefrontal cortex index inhibitory control, and how chronic stress reorganizes those signals.
Liu et al., 2025, Nature Communications
a Diagram of GRABNE and GRABACh recording. Used with permission of Elsevier, from the Mouse Brain in Stereotaxic Coordinates, Franklin and Paxinos, 2007; permission conveyed through Copyright Clearance Center, Inc.
b Histological confirmation of expression of GRABNE and GRABACh in the prefrontal cortex.
c Example heatmap of NE and ACh responses to water rewards.
d NE and ACh dynamics around water rewards. 25 sessions from 7 animals.
e NE and ACh peak responses (top; p = 0.22, two-sided Wilcoxon signed-rank test) and their latencies (bottom; p = 0.03, two-sided Wilcoxon signed-rank test) to water rewards. 25 sessions from 7 animals.
f Example traces of simultaneously recorded NE, ACh, and pupil size. Inset: spectrum of NE and ACh signals.
g Cross-correlogram between NE and ACh signals. Both peak correlation coefficient (p = 1.3e-4, two-sided Wilcoxon signed-rank test) and latency (p = 5.6e-3, two-sided Wilcoxon signed-rank test) are greater than 0. 165 sessions from 19 animals. Shaded area around 0 indicates 99.7% confidence interval.
h Coherence between NE and ACh signals. 165 sessions from 19 animals. Shaded area around 0 indicates 99.7% confidence interval.
i, j Cross-correlogram between NE/ACh signals and pupil size. p = 6.3e-4, two-sided paired t-test for peak correlation coefficients and p = 3.4e-4, two-sided paired t-test for cross-correlation lags. 111 sessions from 19 animals for (i–m). Horizontal shaded area around 0 indicates 99.7% confidence interval.
k, l Cross-correlogram between NE/ACh signals and the first derivative of pupil size. P = 0.12, two-sided paired t-test for peak correlation coefficients and p = 2.9e-4, two-sided paired t-test for cross-correlogram lags. Shaded area around 0 indicates 99.7% confidence interval.
m Example image of the pupil of a mouse (top) and the phase relationship between prefrontal NE/ACh signals and pupil fluctuations (bottom). Error bars and shaded areas indicate ±SEM. unless otherwise indicated.