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      Circadian Phase Shifts to Neuropeptide Y In Vitro: Cellular Communication and Signal Transduction

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          Abstract

          Mammalian circadian rhythms originate in the hypothalamic suprachiasmatic nuclei (SCN), from which rhythmic neural activity can be recorded in vitro. Application of neurochemicals can reset this rhythm. Here we determine cellular correlates of the phase-shifting properties of neuropeptide Y (NPY) on the hamster circadian clock in vitro. Drug or control treatments were applied to hypothalamic slices containing the SCN on the first day in vitro. The firing rates of individual cells were sampled on the second day in vitro. Control slices exhibited a peak in firing rate in the middle of the day. Microdrop application of NPY to the SCN phase advanced the time of peak firing rate. This phase-shifting effect of NPY was not altered by block of sodium channels with tetrodotoxin or block of calcium channels with cadmium and nickel, consistent with a direct postsynaptic site of action. Pretreatment with the glutamate receptor antagonists ( dl-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione disodium) also did not alter phase shifts to NPY. Blocking GABA A receptors with bicuculline (Bic) had effects only at very high (millimolar) doses of Bic, whereas blocking GABA B receptors did not alter effects of NPY. Phase shifts to NPY were blocked by pretreatment with inhibitors of protein kinase C (PKC), suggesting that PKC activation may be necessary for these effects. Bathing the slice in low Ca 2+/high Mg 2+ can block phase shifts to NPY, possibly via a depolarizing action. A depolarizing high K + bath can also block NPY phase shifts. The results are consistent with direct action of NPY on pacemaker neurons, mediated through a signal transduction pathway that depends on activation of PKC.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          1 November 1997
          : 17
          : 21
          : 8468-8475
          Affiliations
          [ 1 ]Department of Psychology, Clark Science Center, Smith College, Northampton, MA 01063
          Article
          PMC6573727 PMC6573727 6573727
          10.1523/JNEUROSCI.17-21-08468.1997
          6573727
          9334419
          87efa5ae-7408-48de-b040-5384d0268375
          Copyright © 1997 Society for Neuroscience
          History
          : 9 June 1997
          : 4 August 1997
          : 11 August 1997
          Categories
          Articles

          phase shift,PKC,calcium,circadian,glutamate,neuropeptide Y,TTX,GABA,hamster,suprachiasmatic nucleus

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