Address: office 1410a, 17 Naberezhnaya Severnoy Dviny, Arkhangelsk, 163002, Russian Federation, Northern (Arctic) Federal University named after M.V. Lomonosov

Phone: (818-2) 21-61-21


Modulatory Effect of Neuropeptide Y on the Bioelectric Activity of Neurons in Rat Hypothalamic Suprachiasmatic Nucleus. P. 79–86

Версия для печати

Section: Medical and biological sciences




Al’bina А. Petrova*, Aleksey N. Inyushkin*
*Samara National Research University (Samara, Russian Federation)
Corresponding author: Aleksey Inyushkin; address: ul. Akademika Pavlova 1, Samara, 443011, Russian Federation;


This paper assessed the role of neuropeptide Y as an entraining factor for neurons in the hypothalamic suprachiasmatic nucleus – the main circadian oscillator in humans and mammals. We studied the effect of 10 nM neuropeptide Y applications on spike activity and spike code parameters of neurons in rat suprachiasmatic nucleus in vitro. We used our own approach to the analysis of spike activity, which consists in calculating the distribution entropy of interspike intervals and mutual information between adjacent interspike intervals along with the determination of mean spike frequency. This allowed us to investigate the effect produced by neuropeptide Y not only on the level of cell activity, but also on the degree of irregularity in the generation of action potentials and on the patterning of spike activity. The analysis of the effect of neuropeptide Y revealed two types of response: a decrease (in 43.2 % of neurons) and an increase (in 9.9 % of neurons) in mean spike frequency. The rest of the neurons (46.9 %) had no changes in this activity parameter. In all recorded cells, treated as a single group (n = 81), a statistically significant decrease in the level of activity and an increase in mutual information between adjacent interspike intervals were revealed. The results obtained show that neuropeptide Y can influence the level of spike activity and spike code parameters of neurons in the hypothalamic suprachiasmatic nucleus.


neuropeptide Y, circadian rhythms, brain neurons, spike activity, suprachiasmatic nucleus
Download (pdf, 1.3MB )


  1. Tatemoto K., Calquist M., Mutt V. Neuropeptide Y – a Novel Brain Peptide with Structural Similarities to Peptide YY and Pancreatic Polypeptide. Nature, 1982, vol. 296, no. 5858, pp. 659–660. 
  2. Larsson T.A., Olsson F., Sundstrom G., Lundin L.G., Brenner S., Venkatesh B., Larhammar D. Early Vertebrate Chromosome Duplications and the Evolution of the Neuropeptide Y Receptor Gene Regions. BMC Evol. Biol., 2008, vol. 8. Art. no. 184. 
  3. Wahlestedt C., Reis D.J. Neuropeptide Y-Related Peptides and Their Receptors – Are the Receptors Potential Therapeutic Drug Targets? Annu. Rev. Pharmacol. Toxicol., 1993, vol. 33, pp. 309–352. 
  4. Pu S., Jain M.R., Horvath T.L., Diano S., Kalra P.S., Kalra S.P. Interactions Between Neuropeptide Y and Gamma- Aminobutyric Acid in Stimulation of Feeding: A Morphological and Pharmacological Analysis. Endocrinology, 1999, vol. 140, no. 2, pp. 933–940. 
  5. Hexum T.D., Majane E.A., Russett L.R., Yang H.Y. Neuropeptide Y Release from the Adrenal Medulla After Cholinergic Receptor Stimulation. J. Pharmacol. Exp. Ther., 1987, vol. 243, no. 3, pp. 927–930. 
  6. Myers A.K., Torres Duarte A.P., Zukowska-Grojec Z. Immunoreactive Neuropeptide Y (NPY) in Plasma and Platelets of Rat and Mouse Strains and Human Volunteers. Regul. Pept., 1993, vol. 47, no. 3, pp. 239–245. 
  7. Larhammar D., Fredriksson R., Larson E.T., Salaneck E. Phylogeny of NPY-Family Peptides and Their Receptors. Neuropeptide Y and Related Peptides. Berlin, 2004, pp. 75–100. 
  8. Larhammar D., Wraith A., Berglund M.M., Holmberg S.K.S., Lundell I. Origins of the Many NPY-Family Receptors in Mammals. Peptides, 2001, vol. 22, no. 3, pp. 295–307. 
  9. Redrobe J.P., Dumont Y., Quirion R. Neuropeptide Y (NPY) and Depression: From Animal Studies to the Human Condition. Life Sci., 2002, vol. 71, no. 25, pp. 2921–2937. 
  10. McDermott B.J., Bell D. NPY and Cardiac Diseases. Curr. Top. Med. Chem., 2007, vol. 7, no. 17, pp. 1692–1703. 
  11. Leibowitz S.F. Hypothalamic Neuropeptide Y in Relation to Energy Balance. Ann. N. Y. Acad. Sci., 1990, vol. 611, pp. 284–301. 
  12. Edelstein K., Amir S. The Role of the Intergeniculate Leaflet in Entrainment of Circadian Rhythms to a Skeleton Photoperiod. J. Neurosci., 1999, vol. 19, no. 1, pp. 372–380. 
  13. Card J.P., Moore R.Y. Organization of Lateral Geniculate-Hypothalamic Connections in the Rat. J. Comp. Neurol., 1989, vol. 284, no. 1, pp. 135–147. 
  14. Shinohara K., Tominaga K., Isobe Y. Inouye, S-I.T. Photic Regulation of Peptides Located in the Ventrolateral Subdivision of the Suprachiasmatic Nucleus of the Rat: Daily Variations of Vasoactive Intestinal Polypeptide, Gastrin- Releasing Peptide and Neuropeptide Y. J. Neurosci., 1993, vol. 13, no. 2, pp. 793–800. 
  15. Golombek D.A., Biello S.M., Rendon R.A., Harrington M.E. Neuropeptide Y Phase Shifts the Circadian Clock in vitro via a Y2 Receptor. Neuroreport, 1996, vol. 7, no. 7, pp. 1315–1319. 
  16. Gribkoff V.K., Pieschl R.L., Wisialowski T.A., van den Pol A.N., Yocca F.D. Phase Shifting of Circadian Rhythms and Depression of Neuronal Activity in the Rat Suprachiasmatic Nucleus by Neuropeptide Y: Mediation by Different Receptor Subtypes. J. Neurosci., 1998, vol. 18, no. 8, pp. 3014–3022. 
  17. Bhumbra G.S., Dyball R.E.D. Spike Coding from Perspective of a Neurone. Cogn. Process., 2005, vol. 6, no. 3, pp. 157–176. 
  18. Bhumbra G.S., Inyushkin A.N., Dyball R.E.D. Assessment of Spike Activity in the Supraoptic Nucleus. J. Neuroendocrinol., 2004, vol. 16, no. 4, pp. 390–397. 
  19. Bhumbra G.S., Inyushkin A.N., Saeb-Parsy K., Hon A., Dyball R.E.D. Rhythmic Changes in Spike Coding in the Rat Suprachiasmatic Nucleus. J. Physiol., 2005, vol. 563, no. 1, pp. 291–307. 
  20. Inyushkin A.N., Bhumbra G.S., Dyball R.E.D. Leptin Modulates Spike Coding in the Rat Suprachiasmatic Nucleus. J. Neuroendocrinol., 2009, vol. 21, no. 8, pp. 705–714. 
  21. Inyushkin A.N., Bhumbra G.S., Gonzalez J.A., Dyball R.E.D. Melatonin Modulates Spike Coding in the Rat Suprachiasmatic Nucleus. J. Neuroendocrinol., 2007, vol. 19, no. 9, pp. 671–681. 
  22. Obrietan K., van den Pol A.N. Neuropeptide Y Depresses GABA-Mediated Calcium Transients in Developing Suprachiasmatic Nucleus Neurons: A Novel Form of Calcium Long-Term Depression. J. Neurosci., 1996, vol. 16, no. 10, pp. 3521–3533. 
  23. Toth P.T., Bindokas V.P., Bleakman D., Colmers W.F., Miller R.J. Mechanism of Presynaptic Inhibition by Neuropeptide Y at Sympathetic Nerve Terminals. Nature, 1993, vol. 364, pp. 635–639. 
  24. Colmers W.F., Bleakman D. Effects of Neuropeptide Y on the Electrical Properties of Neurons. Trends Neurosci., 1994, no. 17, no. 9, pp. 373–379. 
  25. Rhim H., Kinney G.A., Emmerson P.J., Miller R.J. Regulation of Neurotransmission in the Arcuate Nucleus of the Rat by Different Neuropeptide Y Receptors. J. Neurosci., 1997, vol. 17, no. 9, pp. 2980–2989. 
  26. Zidichouski J.A., Chen H., Smith P.A. Neuropeptide Y Activates Inwardly-Rectifying K+-Channels in C-Cells of Amphibian Sympathetic Ganglia. Neurosci. Lett., 1990, vol. 117, no. 1–2, pp. 123–128. 
  27. Acuna-Goycolea C., Tamamaki N., Yanagawa Y., Obata K., van den Pol A.N. Mechanisms of Neuropeptide Y, Peptide YY, and Pancreatic Polypeptide Inhibition of Identified Green Fluorescent Protein-Expressing GABA Neurons in the Hypothalamic Neuroendocrine Arcuate Nucleus. J. Neurosci., 2005, vol. 25, no. 32, pp. 7406–7419. 
  28. Paredes M.F., Greenwood J., Baraban S.C. Neuropeptide Y Modulates a G Protein-Coupled Inwardly Rectifying Potassium Current in the Mouse Hippocampus. Neurosci. Lett., 2003, vol. 340, no. 1, pp. 9–12. 
  29. Sosulina L., Schwesig G., Seifert G., Pape H.C. Neuropeptide Y Activates a G-Protein-Coupled Inwardly Rectifying Potassium Current and Dampens Excitability in the Lateral Amygdala. Mol. Cell. Neurosci., 2008, vol. 39, no. 3, pp. 491–498. 
  30. Huang C.-L., Slesinger P.A., Casey P.J., Jan Y.N., Jan L.Y. Evidence That Direct Binding of Gβγ to the GIRK1 G Protein- Gated Inwardly Rectifying K+ Channel Is Important for Channel Activation. Neuron, 1995, vol. 15, no. 5, pp. 1133–1143. 
  31. Sun Q.Q., Baraban S.C., Prince D.A., Huguenard J.R. Target-Specific Neuropeptide Y-Ergic Synaptic Inhibition and Its Network Consequences Within the Mammalian Thalamus. J. Neurosci., 2003, vol. 23, no. 29, pp. 9639–9649. 
  32. Colmers W.F., Klapstein G.J., Fournier A., St.-Pierre S., Treherne K.A. Presynaptic Inhibition by Neuropeptide Y in Rat Hippocampal Slice in vitro Is Mediated by a Y2 Receptor. Br. J. Pharmacol., 1991, vol. 102, no. 1, pp. 41–44. 
  33. Ikeda S.R. Voltage-Dependent Modulation of N-Type Calcium Channels by G-Protein βγ Subunits. Nature, 1996, vol. 380, no. 6571, pp. 255–258. 
  34. Scholz K.P., Miller R.J. Inhibition of Quantal Transmitter Release in the Absence of Calcium Influx by a G Protein-Linked Adenosine Receptor at Hippocampal Synapses. Neuron, 1992. vol. 8, no. 6, pp. 1139–1150.