On the intrinsic regulation of neuropeptide Y release in the mammalian suprachiasmatic nucleus circadian clock

Apr 10, 2010The European journal of neuroscience

How the body controls release of a key signaling chemical in the brain’s daily rhythm center

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Abstract

Neuropeptide Y (NPY) release in the hamster suprachiasmatic nucleus (SCN) exhibits a daily rhythm influenced by light and behavioral stimuli.

NPY release in the SCN is rhythmic under a 14L : 10D light cycle, peaking shortly after lights-on and reaching a low point at midday.
No rhythmic change in NPY release was observed under constant darkness.
Behaviors such as wheel-running at midday, which induce serotonin release from the intergeniculate leaflet (IGL), significantly increase NPY release in the SCN.
Application of the serotonin agonist (+/-)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT) enhances NPY release in the SCN.
Blocking serotonin receptors with the antagonist metergoline prevents the increase in SCN NPY release triggered by wheel-running.
GABA activity suppression through muscimol administration reduces NPY release in the SCN, suggesting a regulatory mechanism involving serotonergic activity.

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Timing of the circadian clock of the suprachiasmatic nucleus (SCN) is regulated by photic and non-photic inputs. Of these, neuropeptide Y (NPY) signaling from the intergeniculate leaflet (IGL) to the SCN plays a prominent role. Although NPY is critical to clock regulation, neither the mechanisms modulating IGL NPY neuronal activity nor the nature of regulatory NPY signaling in the SCN clock are understood, as NPY release in the SCN has never been measured. Here, microdialysis procedures for in vivo measurement of NPY were used in complementary experiments to address these questions. First, neuronal release of NPY in the hamster SCN was rhythmic under a 14L : 10D photocycle, with the acrophase soon after lights-on and the nadir at midday. No rhythmic fluctuation in NPY occurred under constant darkness. Second, a behavioral phase-resetting stimulus (wheel-running at midday that induces IGL serotonin release) acutely stimulated SCN NPY release. 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 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 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.

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On the intrinsic regulation of neuropeptide Y release in the mammalian suprachiasmatic nucleus circadian clock

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