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Papers of the Week

Papers: 27 Apr 2019 - 3 May 2019

Animal Studies

2019 Jun 05




Editor's Pick

Microcircuit Mechanisms through which Mediodorsal Thalamic Input to Anterior Cingulate Cortex Exacerbates Pain-Related Aversion.


Meda KS, Patel T, Braz JM, Malik R, Turner ML, Seifikar H, Basbaum AI, Sohal VS
Neuron. 2019 Jun 05; 102(5):944-959.e3.
PMID: 31030955.


Hyperexcitability of the anterior cingulate cortex (ACC) is thought to drive aversion associated with chronic neuropathic pain. Here, we studied the contribution of input from the mediodorsal thalamus (MD) to ACC, using sciatic nerve injury and chemotherapy-induced mouse models of neuropathic pain. Activating MD inputs elicited pain-related aversion in both models. Unexpectedly, excitatory responses of layer V ACC neurons to MD inputs were significantly weaker in pain models compared to controls. This caused the ratio between excitation and feedforward inhibition elicited by MD input to shift toward inhibition, specifically for subcortically projecting (SC) layer V neurons. Furthermore, direct inhibition of SC neurons reproduced the pain-related aversion elicited by activating MD inputs. Finally, both the ability to elicit pain-related aversion and the decrease in excitation were specific to MD inputs; activating basolateral amygdala inputs produced opposite effects. Thus, chronic pain-related aversion may reflect activity changes in specific pathways, rather than generalized ACC hyperactivity.