Figure 1.

Cellular mechanism for the excessive excitability in the lateral habenular neurons. (A) Coronal section of the adult mouse brain showing the anatomical position of the medial and lateral habenulae by Nissl staining. (B) Schematic diagram showing the orientation of the MHb and LHb receiving the inputs from GPi/EPN, DB and LH and projecting to the brain stem nuclei. LHb neurons also receive ascending afferent fibers from the serotonergic raphe nuclei. (C) Schematic diagram showing molecules essential in the glutamatergic synaptic transmission. Glutamate (red dots) is transported into the synaptic vesicle at the axonal terminal of presynaptic neurons by vesicular glutamate transporter 2 (black rectangles, Vglut2). Serotonin (green dots) acts on the presynaptic axonal terminal through serotonin receptors (light green rectangles, 5-hydroxytryptamine (serotonin) receptor (5HTR)) to inhibit the excitatory transmission. Released glutamate binds and activates the a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptor containing GluR1 subunit (pink rectangles) whose recruitment to the synapse is regulated by β form of calcium/calmodulin-dependent kinase II (βCaMKII). Glutamate transporters (brown rectangles) expressed in astrocytes (GLT-1 and GLAST) and neurons (EAAC1) clear the glutamate released to synaptic cleft.