GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment

Abstract

A pathway that controls our mood A brain area called the lateral habenula is involved in negative motivation and may thus play a role in depression. Shabel et al. investigated synaptic transmission in a brain pathway to the lateral habenula that transmits disappointment signals. Surprisingly, they found the simultaneous release of two antagonistic substances, glutamate and GABA, from individual nerve cells. In an animal model of depression, GABA release was reduced in this pathway. A widely used antidepressant drug, however, increased GABA co-release. These results reveal an unusual synaptic mechanism that affects lateral habenula activity. This mechanism may be instrumental for regulating the emotional impact of disappointment. Science , this issue p. 1494