Third, bilateral IGL microinjection of the serotonin agonist, (±)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene

(8-OH-DPAT) (another non-photic phase-resetting stimulant), at midday enhanced SCN NPY release. Conversely, similar application of the serotonin antagonist, metergoline, abolished wheel-running-induced SCN NPY release. IGL microinjection of the GABA agonist, muscimol, suppressed Protein Tyrosine Kinase inhibitor SCN NPY release. These results support an intra-IGL mechanism whereby behavior-induced serotonergic activity suppresses inhibitory GABAergic transmission, promoting NPY activity and subsequent phase resetting. Collectively, these results confirm IGL-mediated NPY release in the SCN and verify that PARP inhibitor trial its daily rhythm of release is dependent upon the 14L : 10D photocycle, and that it is modulated by appropriately-timed phase-resetting behavior, probably mediated by serotonergic activation of NPY units in the IGL. “
“Champalimaud Centre for the Unknown, Champalimaud Neuroscience Programme, Lisboa, Portugal The neurotransmitter serotonin

plays an important role in modulating diverse behavioral traits. Mice lacking the serotonin 1A receptor (Htr1a) show elevated avoidance of novel open spaces, suggesting that it has a role in modulating anxiety behavior. Htr1a is a Gαi-coupled G-protein-coupled receptor expressed on serotonin neurons (auto-receptor), where it mediates negative feedback of serotonin neuron firing. Htr1a is also expressed on non-serotonin neurons (hetero-receptor) in diverse brain regions, where it mediates an inhibitory effect of serotonin on neuronal activity. Debate exists about which of these receptor

populations is responsible for the modulatory effects of Htr1a on anxiety. Studies using tissue-specific transgenic expression have suggested that forebrain Htr1a hetero-receptors are sufficient to restore normal anxiety behavior to Htr1a knockout mice. At the same time, experiments using tissue-specific transgenic suppression much of Htr1a expression have demonstrated that Htr1a auto-receptors, but not forebrain hetero-receptors, are necessary for normal anxiety behavior. One interpretation of these data is that multiple Htr1a receptor populations are involved in modulating anxiety. Here, we aimed to test this hypothesis by determining whether Htr1a auto-receptors are sufficient to restore normal anxiety to Htr1a knockout animals. Transgenic mice expressing Htr1a under the control of the tryptophan hydroxylase 2 (Tph2) promoter showed restored Htr1a-mediated serotonin negative feedback and hypothermia, but anxiety behavior indistinguishable from that of knockout mice. These data show that, in the absence of Htr1a hetero-receptors, auto-receptors are unable to have an impact on anxiety. When combined with previous data, these findings support the hypothesis that Htr1a auto-receptors are necessary, but not sufficient, to modulate anxiety.