This Week in The Journal

Inhibitory GABA A receptors in the central nervous system are usually composed of two alpha, two beta, and one gamma subunits.These subunits are heterogeneous: there are six different alpha subtypes, three beta subtypes, and three gamma subtypes.The composition of GABA A receptors is important clinically because the subunits can be distinctly targeted by treatments for different disease symptoms.Benzodiazepines (BDZs) target GABA A receptors, strengthening their signaling.Alpha subunits and gamma subunits together contribute to BDZ binding on GABA A receptors, but gamma subunits have received less research attention.Neumann and colleagues address this oversight.They identified a unique GABA A receptor in the spinal dorsal horn, a key site for pain processing.Using mice, the authors found that gamma 1-containing GABA A receptors were highly expressed in this region.Furthermore, they sufficiently supported synaptic clustering of GABA A receptors and BDZ action when gamma 2-containing GABA A receptors in the spinal cord were ablated.These findings suggest that gamma 1-containing GABA A receptors contribute to functionally relevant pain processing circuits.This is a major preclinical advancement and may inform treatment development for pain.