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Previous Article
Volume 16, Number 18,
Issue of September 15, 1996
pp. 5883-5895
Copyright ©1996 Society for Neuroscience
Neuropeptide Y-Mediated Long-Term Depression of Excitatory
Activity in Suprachiasmatic Nucleus Neurons
Received May 9, 1996; revised June 21, 1996; accepted June 25, 1996.
Anthony N. van den Pol1, 2,
Karl Obrietan2,
Gong Chen1, and
Andrei B.
Belousov2
1 Section of Neurosurgery, Yale University School of
Medicine, New Haven, Connecticut 06520, and 2 Department of
Biological Sciences, Stanford University, Stanford, California
94305
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 n)
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-like receptors, were short term and recovered rapidly. The primary
site of long-term NPY actions may be on presynaptic glutamatergic
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.
Key words:
suprachiasmatic nucleus;
mammalian circadian clock;
glutamate;
NPY;
LTD;
learning biological clock;
phase-shift;
neuroendocrine;
hypothalamus
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