Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states

Nat Neurosci. 2021 Apr;24(4):542-553. doi: 10.1038/s41593-021-00811-x. Epub 2021 Mar 8.

Abstract

In humans, tissue injury and depression can both cause pain hypersensitivity, but whether this involves distinct circuits remains unknown. Here, we identify two discrete glutamatergic neuronal circuits in male mice: a projection from the posterior thalamic nucleus (POGlu) to primary somatosensory cortex glutamatergic neurons (S1Glu) mediates allodynia from tissue injury, whereas a pathway from the parafascicular thalamic nucleus (PFGlu) to anterior cingulate cortex GABA-containing neurons to glutamatergic neurons (ACCGABA→Glu) mediates allodynia associated with a depression-like state. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that POGlu and PFGlu populations undergo different adaptations in the two conditions. Artificial manipulation of each circuit affects allodynia resulting from either tissue injury or depression-like states, but not both. Our study demonstrates that the distinct thalamocortical circuits POGlu→S1Glu and PFGlu→ACCGABA→Glu subserve allodynia associated with tissue injury and depression-like states, respectively, thus providing insights into the circuit basis of pathological pain resulting from different etiologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Depression / physiopathology*
  • Hyperalgesia / physiopathology*
  • Male
  • Mice
  • Neural Pathways / physiology*
  • Neurons / physiology
  • Somatosensory Cortex / physiology*
  • Thalamus / physiology*