A Central Amygdala Input to the Parafascicular Nucleus Controls Comorbid Pain in Depression

Abstract

While comorbid pain in depression (CP) occurs at a high rate worldwide, the neural connections underlying the core symptoms of CP have yet to be elucidated. Here, we define a pathway whereby GABAergic neurons from the central nucleus of the amygdala (GABA^CeA) project to glutamatergic neurons in the parafascicular nucleus (Glu^PF). These Glu^PF neurons relay directly to neurons in the second somatosensory cortex (S2), a well-known area involved in pain signal processing. Enhanced inhibition of the GABA^CeA→Glu^PF→S2 pathway is found in mice exhibiting CP symptoms. Reversing this pathway using chemogenetic or optogenetic approaches alleviates CP symptoms. Together, the current study demonstrates the putative importance of the GABA^CeA→Glu^PF→S2 pathway in controlling at least some aspects of CP.

Keywords: GABA neurons; central nucleus of the amygdala; chemogenetics; comorbid pain; glutamate neurons; neural circuits; optogenetics; parafascicular nucleus; retrograde trans-monosynaptic tracing; second somatosensory cortex.