Distribution and Functional Characterization of Melatonin Receptors in the Rodent Habenula
Evely, Katherine M.
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Melatonin (MLT) is rhythmically secreted from the pineal gland and mediates its physiological effects through two G protein-coupled receptors, termed MT 1 and MT 2 . Melatonin receptors are expressed in several brain areas, including the habenula, a paired nuclei located anterior to the melatonin secreting pineal gland and adjacent to the dorsal third ventricle. The habenula is viewed as a relay-station from forebrain to midbrain and has been shown to modulate various neurotransmitter systems and a plethora of behaviors, including sleep, mood and pain. The goal of our research is to investigate the distribution and function of habenular melatonin receptors. To that end, we first used brain tissue from a C3H/HeN transgenic mouse line expressing red fluorescence protein (RFP) at the MT 1 receptor promoter to map receptor distribution. In addition, an electrophysiological approach was used to study the effect of melatonin on the excitability of habenular neurons of Sprague-Dawley rats. RFP-MT 1 fluorescence and immunoreactivity was localized to the medial habenula (MHb) and habenula commissure (HbC). Immunofluorescence co-staining for RFP along with choline acetyl transferase (ChAT) or vesicular glutamate transporter 2 (VGLUT2) was used to investigate the distribution of the MT 1 receptor. Results show RFP-MT 1 expression in the dorsal MHb, clearly separated from ChAT fluorescence in the ventral MHb. VGLUT2 and RFP-MT1 cells are present in dorsal MHb neurons. Whole cell recordings from brain slices of juvenile rats were performed to explore melatonin receptor functionality. Our results show an increase in the average amplitude of evoked excitatory post-synaptic currents (EPSC) in response to 1 μM melatonin treatment. The increase in amplitude was accompanied by a decrease in the paired pulse ratio, suggesting that the change in amplitude is a result of increased glutamate release. These results indicate that activation of melatonin receptors in the habenula modulates synaptic strength. Together, the data show that melatonin receptors are expressed in the habenula and may play a prominent role in regulating glutamatergic input to the habenula, an integrative center for modulation of various behaviors.