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Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus

Abstract

The degree of behavioral control that an organism has over a stressor is a potent modulator of the stressor's impact; uncontrollable stressors produce numerous outcomes that do not occur if the stressor is controllable. Research on controllability has focused on brainstem nuclei such as the dorsal raphe nucleus (DRN). Here we find that the infralimbic and prelimbic regions of the ventral medial prefrontal cortex (mPFCv) in rats detect whether a stressor is under the organism's control. When a stressor is controllable, stress-induced activation of the DRN is inhibited by the mPFCv, and the behavioral sequelae of uncontrollable stress are blocked. This suggests a new function for the mPFCv and implies that the presence of control inhibits stress-induced neural activity in brainstem nuclei, in contrast to the prevalent view that such activity is induced by a lack of control.

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Figure 1: Efficiency of wheel-turn escape behavior during exposure to controllable tailshock in rats that had received mPFCv muscimol or vehicle 60 min before the shock session.
Figure 2: Placements of microinjection cannula and microdialysis probe.
Figure 3: Percentage of neurons double-labeled for 5-HT and c-Fos (mean ± s.e.m).
Figure 4: 5-HT as a percentage of baseline in the DRN.
Figure 5: The mean (± s.e.m) number of 8-s intervals spent freezing, in 2-min blocks, after two footshocks 24 h after stressor exposure.
Figure 6: Mean (± s.e.m) shuttlebox escape latencies across blocks of five shuttlebox FR-2 escape trails 24 h after stressor exposure.

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Acknowledgements

We would like to thank J. Rudy for many helpful comments and discussions. This work was supported by US National Institutes of Health grants DA13159 and MH50479.

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Correspondence to S F Maier.

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Amat, J., Baratta, M., Paul, E. et al. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci 8, 365–371 (2005). https://doi.org/10.1038/nn1399

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