The balance of two neurotransmitters released by the same neurons may tilt a brain toward or away from depression, reports a study in Science published September 19th. The study, which included the work of 2013 Foundation NARSAD Young Investigator Grantee Christophe Proulx, Ph.D., of the University of California at San Diego, focuses on a brain region called the lateral habenula (LHb), which has been implicated in depression. In animal models of depression, too much activity in the LHb has been associated with depression-like behavior.

To explore ways to dampen LHb activity, the researchers looked to the neurons sending signals to it, and found something unusual: some neurons were releasing not just one but both of the two major neurotransmitters—glutamate, which excites neurons on the receiving end of the message, and GABA, which inhibits them. This had only previously been found in a small fraction of the billions of neurons in the brain.

Dr. Proulx and colleagues determined this by examining the tiny terminals at which one neuron connects with another. GABA and glutamate molecules resided in the same vesicles, which are then released onto the receiving neuron. This co-release produced mixed signals in the LHb neurons.

The relative balance of GABA and glutamate signals in these terminals might sway mood. For example, the researchers found that the antidepressant citalopram promoted the GABA signal over the glutamate one. And in rats bred to show depression-like behavior, the GABA signal was weaker. This suggests that controlling the relative amounts of GABA and glutamate released by these unusual inputs could influence LHb activity, and potentially mood.

 

Read the abstract of this research paper.