Neuropeptide Y-mediated long-term depression of excitatory activity in suprachiasmatic nucleus neurons

Anthony N. Van Den Pol, Karl Obrietan, Gong Chen, Andrei B. Belousov

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A brief exposure to light can shift the phase of mammalian circadian rhythms by 1 hr or more. Neuropeptide Y (NPY) administration to the hypothalamic suprachiasmatic nucleus, the circadian clock in the brain, also causes a phase shift in circadian rhythms. After a phase shift, the neural clock responds differently to light, suggesting that learning has occurred in neural circuits related to clock function. Thus, certain stimuli can produce effects that last for an extended period, but possible mechanisms of this long-term effect have not been previously examined at the cellular level. Here, we report that NPY caused a long-term depression in both electrical activity and intracellular calcium levels of neurons, as studied with whole- cell patch-clamp recording and Fura-2 digital imaging. In contrast to the immediate (1 sec) recovery after relief from glutamate receptor blockade, a brief single application of NPY(100 nM) depressed cytosolic Ca2 for >1 hr. The mechanism of this long-term calcium depression, a form of cellular learning, is dependent on the simultaneous release of glutamate and activation of NPY receptors, because both the extended response to NPY and any aftereffect were blocked by coapplication of glutamate receptor antagonists. Postsynaptic actions of NPY, mediated by both Y1- and Y2-1ike receptors, were short term and recovered rapidly. The primary site of long- term NPY actions may be on presynaptic glutametergic axons, because the frequency of miniature excitatory postsynaptic currents in the presence of tetrodotoxin was reduced by transient exposure to NPY in both cultures and slices.

Original languageEnglish (US)
Pages (from-to)5883-5895
Number of pages13
JournalJournal of Neuroscience
Issue number18
StatePublished - Sep 15 1996

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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