A receptor believed to be linked to negative moods, in a part of the brain that is little-understood, has been uncovered by an international research team. The discovery[1] could lead to more targeted medications.

The pea-sized receptor was found in a little-studied region in the center of the human brain, the medial habenula.

“The function of the medial habenula is not very well understood but is thought to be related to negative motivational states,"

said first author Dr. Yo Otsu.

NMDA Receptors

The finding is the culmination of eight years of painstaking investigation involving Dr. Otsu, now with the University of Sydney and Kolling Institute, and researchers from France, Canada and Hungary, under the direction of Dr. Marco Diana.

“We knew there were GluN3A subunits in the adult medial habenula and NMDA receptors formed with these subunits were likely to have different characteristics. We did not expect to find the receptor that we did,"

said Dr. Otsu.

NMDA receptors normally require two different neurotransmitter molecules — glutamate and glycine — to bind and activate the receptor.

The receptor that Dr. Otsu and his colleagues found only needs one neurotransmitter — glycine — to activate it.

“Receptors direct brain function and are the target of approximately 40 percent of all current medicines. Therefore, the discovery of this rare type of receptor and its role in modulating anxiety and the effects of negative experiences means it has the potential to be a highly specific target for mood regulating drugs,"

he said.

Side Effects

Psychiatric drugs, Dr. Otsu, explained, frequently come with side effects because they are not targeted to specific areas, affecting the whole brain. The new finding holds the possibility of creating much more specific medicines with less side effects.

“The findings may also have implications for future medications to reduce pain with the receptor subunit found in a part of the brain known to contribute to pain. We will now be embarking on research within the Kolling Institute to further understand the role of this newly found receptor, with the ultimate goal of developing drugs to target it. This could lead to advances in mental health and pain medications,"

he said.

[1] Y. Otsu, E. Darcq, K. Pietrajtis, F. Mátyás, E. Schwartz, T. Bessaih, S. Abi Gerges, C. V. Rousseau, T. Grand, S. Dieudonné, P. Paoletti, L. Acsády, C. Agulhon, B. L. Kieffer, M. A. Diana. Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula. Science 11 Oct 2019: Vol. 366, Issue 6462, pp. 250-254 DOI: 10.1126/science.aax1522


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