Glutamatergic Dysfunction of Lateral Habenula Promotes DepressionAuthor(s): Bing Hu, Russell Fitzgerald
Depression is one of the most prevalent neuropsychiatric disorders which can impair working capability of patients. However, the mechanism underlying the onset of depression remains to be elucidated. Traditionally, people pay much attention to monoamine system, but it was inadequate to understand pathophysiology of depression. Located in the dorsal dienchephalic conduction system, the habenula widely connects to brain regions associated with depression and has great impact on them. Accumulating evidence displays that lateral habenula (LHb) was hyperactive during depression in both clinic and preclinic studies. As a predominant excitatory neurotransmitter, glutamate distributes extensively in habenula, especially LHb. Aversive state can activate habenula, which in turn inhibits monoamine neurotransmitter release and induce depression. Therefore, glutamatergic excitatory neurotransmission in habenula plays a key role in depression etiology. Recent studies revealed that dysfunction of the process of glutamatergic neurotransmission triggered depression. Here, we report the progress of studies and recent findings that glutamatergic dysregulation in LHb contributes to depression, including dysregulation of glutamate level and glutamate transport, GABA/ glutamate ratio and GABAA receptor, and AMPAR, CaMKII as well as NMDAR. This will help us to understand the important role of glutamate in onset of depression and provides knowledge to guide future studies.