Scientists find how the brain processes negative events

CONICET/DICYT Together with scientists of the University of California in San Diego (UCSD), Joaquín Piriz, assistant researcher at the Instituto de Fisiología y Biofísica Bernado Houssay [Houssay Physiology and Biophysics Institute of the Faculty of Medicine of the University of Buenos Aires, IFIBIO Houssay, UBA-CONICET] made an important discovery concerning the “disappointment pathway”. They proved how the lateral habenula activity is regulated and its role in depression.

The lateral habenula is a central brain nucleus that “is activated when the result of an action is worse than expected. It sends the signal indicating that an action went wrong, that is to say, it indicates disappointment”, he explains.

The study, conducted by researcher Roberto Malinow (UCSD) and published in Science magazine, showed that in that nucleus there is a simultaneous release of the excitatory (glutamate) and inhibitory (gamma aminobutyric acid, GABA) neurotransmitters, which give opposing orders to the cells. “It is significant because this effect was not described therefore and it opens up a new research fields on the modulation of neuronal activity”, Piriz affirms.

The activity of this nucleus is modulated by the dual release of the neurotransmitters and the perception of disappointment depends on this activity. “The neuron receives both the switch off and on signals at the same time and from the proportion of each depends the response – whether it activates or not-”, he states.

Depression and lateral habenula

In 2011 the same research team, with Piriz as first co-author, published a study in Nature, in which they determined that the hyperactivity of the lateral habenula leads to depression. Now they know this is due to the high proportion of released glutamate.

This new research shows that the administration of antidepressants to laboratory rats turns off the lateral habenula. This is due to the higher release of inhibitory neurotransmitters, which could indicate that the effects of the antidepressants are partially mediated by the “turning off” of this structure.

So far, experimentally, deep brain stimulation – a procedure mainly used for the treatment of Parkinson’s disease- was used in refractory cases, which are the most severe. This procedure improves the symptoms of these patients after inhibiting the activity of the lateral habenula.

This new knowledge could open up the possibility to investigate new therapies to treat cases of depression because it provides accurate information on how the brain responds to negative or disappointing facts, a possible cause for this disease.