Skip to main content
NCBI home page
Cellular and Molecular Neurobiology logoLink to Cellular and Molecular Neurobiology
. 1986 Dec;6(4):363–379. doi: 10.1007/BF00711406

Electrophysiological actions of somatostatin (SRIF) in hippocampus: Anin vitro study

Alan L Mueller 1,2, Dennis D Kunkel 1, Phillip A Schwartzkroin 1,3
PMCID: PMC11567397  PMID: 2881622

Abstract

  1. The electrophysiological actions of somatostatin (somatotropin release inhibiting factor; SRIF) were investigated in thein vitro hippocampal slice preparation. Intracellular recordings were obtained from pyramidal neurons in area CA1 in slices of hippocampus from guinea pigs and rabbits.

  2. Somatostatin, applied via micropressure ejection to CA1 pyramidal-cell somata, was primarily excitatory. The effects, however, were quite variable, with nearly all cells displaying pronounced tachyphylaxis. A majority of cells was depolarized by SRIF, but hyperpolarizations or biphasic depolarization/hyperpolarization responses were also recorded. Only minimal conductance changes were associated with the SRIF-induced voltage changes.

  3. Depletion of SRIF, by injection of the intact animal with cysteamine several hours before preparing slices, resulted in no obvious abnormalities in hippocampal slice electrophysiology.

  4. Our results obtained with application of exogenous SRIF are consistent with the concept that SRIF acts as an excitatory neurotransmitter/neuromodulator in hippocampus. However, our attempts to demonstrate endogenous SRIF action have thus far been unsuccessful.

Key words: somatostatin, hippocampal slice, excitation, local circuit neurons, interneurons

References

  1. Alger, B. E., and Nicoll, R. A. (1982). Pharmacological evidence for two kinds of GABA receptors on rat hippocampal pyramidal cells studiedin vitro.J. Physicol. (Lond.)328125–141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersen, P. (1975). Organization of hippocampal neurons and their interconnections. InThe Hippocampus, Structure and Development, Vol. I (Isaacson, R. L., and Pribam, K. H., Eds.), Plenum Press, New York, pp. 155–175. [Google Scholar]
  3. Andersen, P., Holmqvist, E., and Voorhoeve, P. E. (1966). Entorhinal activation of dentate granule cells.Acta Physiol. Scand.66448–460. [DOI] [PubMed] [Google Scholar]
  4. Andersen, P., Bliss, T. V. P., and Skrede, K. K. (1971). Unit analysis of the hippocampal population spike.Exp. Brain Res.13208–221. [DOI] [PubMed] [Google Scholar]
  5. Andersen, P., Dingledine, R., Gjerstad, L., Langmoen, I. A., and Mosfeldt-Laursen, A. (1980). Two different responses of hippocampal pyramidal cells to application of gamma-aminobutyric acid.J. Physiol. (Lond.)305279–296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ashwood, T. J., Lancaster, B., and Wheal, H. V. (1984).In vivo andin vitro studies on putative interneurons in the rat hippocampus: Possible mediators of feed-forward inhibition.Brain Res.293279–291. [DOI] [PubMed] [Google Scholar]
  7. Beal, M. F., and Martin, J. B. (1984). Depletion of striatal somatostatin by local cysteamine injection.Brain Res.308319–324. [DOI] [PubMed] [Google Scholar]
  8. Benoit, R., Ling, N., Alford, B., and Guilleman, R. (1982). Seven peptides derived from pro-somatostatin in rat brain.Biochem. Biophys. Res. Comm.107944–950. [DOI] [PubMed] [Google Scholar]
  9. Benoit, R., Bohlen, P., Esch, F., and Ling, N. (1984). Neuropeptides derived from prosomatostatin that do not contain the somatostatin 1-14 sequence.Brain Res.31123–29. [DOI] [PubMed] [Google Scholar]
  10. Brownstein, M., Arimura, A., Sato, H., Schally, A. V., and Kizer, J. S. (1975). The regional distribution of somatostatin in the rat brain.Endocrinology961456–1461. [DOI] [PubMed] [Google Scholar]
  11. Catalan, R. E., Aragones, M. D., and Martinez, A. M. (1979). Somatostatin effect on cyclic AMP and cyclic GMP levels in rat brain.Biochim. Biophys. Acta586213–216. [Google Scholar]
  12. Catalan, R. C., Martinez, A. M., and Aragones, M. D. (1983). Inhibition of cyclic AMP-dependent protein kinase by somatostatin in slices of mouse brain: Dependence on extracellular calcium.Neuropharmacology22641–645. [DOI] [PubMed] [Google Scholar]
  13. Chesselet, M.-F., and Reisine, T. D. (1983). Somatostatin regulates dopamine release in rat striatal slices and cat caudate nuclei.J. Neurosci.3232–236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Delfs, J. R., and Dichter, M. A. (1983). Effects of somatostatin on mammalian cortical neurons in culture: Physiological actions and unusual dose-response characteristics.J. Neurosci.31176–1188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dodd, J., and Kelly, J. S. (1978). Is somatostatin an excitatory transmitter in the hippocampus?Nature273674–675. [DOI] [PubMed] [Google Scholar]
  16. Dorn, A., Bernstein, H.-G., Hahn, H.-J., and Kostmann, G. (1979). Occurrence of somatostatin-like immunoreactivity (SLI) in the dorsal hippocampus of the sand rat (Psammomys obesus).Acta Histochem.65276–278. [DOI] [PubMed] [Google Scholar]
  17. Epelbaum, J., Brazeau, P., Tsang, D., Brawer, J., and Martin, J. B. (1977). Subcellular distribution of radioimmunoassayable somatostatin in rat brain.Brain Res.126309–323. [DOI] [PubMed] [Google Scholar]
  18. Epelbaum, J., Arancibia, L. T., Kordon, C., and Enjalbert, A. (1982). Characterization, regional distribution, and subcellular distribution of125I-Tyr1-somatostatin binding sites in rat brain.J. Neurochem.381515–1523. [DOI] [PubMed] [Google Scholar]
  19. Feldman, S. C., Dreyfus, C. F., and Lichtenstein, E. S. (1982). Somatostatin neurons in the rodent hippocampus: Anin vitro andin vivo immunocytochemical study.Neurosci. Lett.3329–34. [DOI] [PubMed] [Google Scholar]
  20. Finley, J. C. W., Maderdrut, J. L., Roger, L. J., and Petrusz, P. (1981). The immunocytochemical localization of somatostatin-containing neurons in the rat central nervous system.Neuroscience62173–2192. [DOI] [PubMed] [Google Scholar]
  21. Gray, T. S. (1983). The morphology of somatostatin-immunoreactive neurons in the lateral nucleus of the rat amygdala.Peptides4663–668. [DOI] [PubMed] [Google Scholar]
  22. Hendrickson, A. E., Hunt, S. P., and Wu, J.-Y. (1981). Immunocytochemical localization of glutamic acid decarboxylase in monkey striate cortex.Nature292605–607. [DOI] [PubMed] [Google Scholar]
  23. Hotson, J. R., Prince, D. A., and Schwartzkroin, P. A. (1979). Anomalous inward rectification in hippocampal neurons.J. Neurophysiol.42889–895. [DOI] [PubMed] [Google Scholar]
  24. Ioffe, S., Havlicek, V., Friesen, H., and Chernick, V. (1977). The excitatory effect of iontophoretically applied somatostatin (SRIF) on cortical neurons in awake unanesthetized animals.Fed. Proc.36364. [Google Scholar]
  25. Ioffe, S., Havlicek, V., Friesen, H., and Chernick, V. (1978). Effect of somatostatin (SRIF) and L-glutamate on neurons of the sensorimotor cortex in awake habituated rabbits.Brain Res.153414–418. [DOI] [PubMed] [Google Scholar]
  26. Iversen, L. L., Iversen, S. D., Bloom, F., Douglas, C., Brown, M., and Vale, W. (1978). Calcium-dependent release of somatostatin and neurotensin from rat brainin vitro.Nature273161–163. [DOI] [PubMed] [Google Scholar]
  27. Katayama, Y., and North, R. A. (1980). The action of somatostatin on neurons of the myenteric plexus of the guinea pig ileum.J. Physiol. Lond.303315–323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kobayashi, R. M., Brown, M., and Vale, W. (1977). Regional distribution of neurotensin and somatostatin in rat brain.Brain Res.126584–588. [DOI] [PubMed] [Google Scholar]
  29. Kohler, C., and Chan-Palay, V. (1982). Somatostatin-like immunoreactive neurons in the hippocampus: An immunocytochemical study in the rat.Neurosci. Lett.34259–264. [DOI] [PubMed] [Google Scholar]
  30. Kondo, H., Katayama, Y., and Yui, R. (1982). On the occurrence and physiological effect of somatostatin in the ciliary ganglion of cats.Brain Res.247141–144. [DOI] [PubMed] [Google Scholar]
  31. Kunkel, D. D., Schwartzkroin, P. A., and Hendrickson, A. E. (1983). Immunocytochemistry of somatostatin in CA1 of rabbit hippocampus.Soc. Neurosci. Abstr.9218. [Google Scholar]
  32. Kunkel, D. D., Hendrickson, A. E., Wu, J.-Y., and Schwartzkroin, P. A. (1986). Glutamic acid decarboxylase (GAD) immunocytochemistry of developing rabbit hippocampus.J. Neurosci.6541–552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lee, S. L., Havlicek, V., Panerai, A. E., and Friesen, H. G. (1978). High K+-induced release of somatostatin from the cortical preparation of rat brain.Experientia35351–352. [DOI] [PubMed] [Google Scholar]
  34. Leroux, P., and Peletier, G. (1984). Radioautographic localization of somatostatin-14 and somatostatin-28 binding sites in the rat brain.Peptides5503–506. [DOI] [PubMed] [Google Scholar]
  35. Lomo, T. (1971). Patterns of activation in a monosynaptic cortical pathway: The perforant path input to the dentate area of the hippocampal formation.Exp. Brain Res.1218–45. [PubMed] [Google Scholar]
  36. Mancillas, J. R., Siggins, G. R., and Bloom, P. E. (1985). Somatostatin-14 directly depresses neuronal discharge but enhances excitatory responses to acetylcholine in the rat cortex and hippocampus.Soc. Neurosci. Abstr.11341. [Google Scholar]
  37. McCaman, R. E., McKenna, D. G., and Ono, J. K. (1977). A pressure system for intracellular and extracellular ejections of picoliter volumes.Brain Res.136141–147. [DOI] [PubMed] [Google Scholar]
  38. Morrison, J. H., Benoit, R., Magistretti, P. J., Ling, N., and Bloom, F. E. (1982). Immunohistochemical distribution of pro-somatostatin-related peptides in hippocampus.Neurosci. Lett.3417–142. [DOI] [PubMed] [Google Scholar]
  39. Morrison, J. H., Benoit, R., Magistretti, P. J., and Bloom, F. E. (1983). Immunohistochemical distribution of pro-somatostatin-related peptides in cerebral cortex.Brain Res.262344–351. [DOI] [PubMed] [Google Scholar]
  40. Mueller, A. L., Taube, J. S., and Schwartzkroin, P. A. (1984). Development of hyperpolarizing inhibitory postsynaptic potentials and hyperpolarizing response to gamma-aminobutyric acid in rabbit hippocampus studiedin vitro.J. Neurosci.4860–867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Nemeth, E. F., and Cooper, J. R. (1979). Effect of somatostatin on acetylcholine release from rat hippocampal synaptosomes.Brain Res.165166–170. [DOI] [PubMed] [Google Scholar]
  42. Olpe, H.-R., Balcar, V. J., Bittiger, H., Rink, H., and Sieber, P. (1980). Central actions of somatostatin.Eur. J. Pharmacol.63127–133. [DOI] [PubMed] [Google Scholar]
  43. Palkovits, M., Brownstein, M. J., Eiden, L. E., Beinfeld, M. C., Russell, J., Arimura, A., and Szabo, S. (1982). Selective depletion of somatostatin in rat brain by cysteamine.Brain Res.240178–180. [DOI] [PubMed] [Google Scholar]
  44. Petrusz, P., Sar, M., Grossman, G. H., and Kizer, J. S. (1977). Synaptic terminals with somatostatin-like immunoreactivity in the rat brain.Brain Res.137181–187. [DOI] [PubMed] [Google Scholar]
  45. Pittman, Q.J., and Siggins, G. R. (1981). Somatostatin hyperpolarizes hippocampal pyramidal cellsin vitro.Brain Res.221402–408. [DOI] [PubMed] [Google Scholar]
  46. Renaud, L. P., Martin, J. B., and Brazeau, P. (1975). Depressant action of TRH, LH-RH, and somatostatin on actitivy of central neurons.Nature255233–235. [DOI] [PubMed] [Google Scholar]
  47. Reubi, J.-C., Perrin, M. H., Rivier, J. E., and Vale, W. (1981). High affinity binding sites for a somatostatin-28 analog in rat brain.Life Sci.282191–2198. [DOI] [PubMed] [Google Scholar]
  48. Roberts, G. W., Woodhams, P. L., Polak, J. M., and Crow, T. J. (1984). Distribution of neuropeptides in the limbic system of the rat: The hippocampus.Neuroscience1135–77. [DOI] [PubMed] [Google Scholar]
  49. Sagar, S. M., Landry, D., Millard, W. J., Badger, T. M., Arnold, M. A., and Martin, J. B. (1982). Depletion of somatostatin-like immunoreactivity in the rat central nervous system by cysteamine.J. Neurosci.2225–231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Schwartzkroin, P. A. (1975). Characteristics of CA1 neurons recorded intracellularly in the hippocampalin vitro slice preparation.Brain Res.85423–436. [DOI] [PubMed] [Google Scholar]
  51. Schwartzkroin, P. A. (1977). Further characteristics of hippocampal CA1 cellsin vitro.Brain Res.12853–68. [DOI] [PubMed] [Google Scholar]
  52. Schwartzkroin, P. A. (1982). Development of rabbit hippocampus: Physiology.Dev. Brain Res.2469–486. [DOI] [PubMed] [Google Scholar]
  53. Schwartzkroin, P. A., and Mathers, L. H. (1978). Physiological and morphological identification of a nonpyramidal hippocampal cell type.Brain Res.1571–10. [DOI] [PubMed] [Google Scholar]
  54. Schwartzkroin, P. A., and Mueller, A. L. (1986). Electrophysiology of hippocampal neurons. InCerebral Cortex (Isaacson, R. L., and Pribram, K. H., Eds.), Plenum Press, New York (in press). [Google Scholar]
  55. Siggins, G. R., and French, E. D. (1984). Pro-somatostatin-related peptides alter the discharge rate of rat cortical and hippocampal neuronsin vivo: An iontophoretic study.Soc. Neurosci. Abstr.10810. [Google Scholar]
  56. Siggins, G. R., McGinty, J. F., Morrison, J. H., Pittman, Q. J., Zeiglgansberger, W., Magistretti, P. J., and Gruol, D. L. (1982). The role of neuropeptides in the hippocampal formation. InRegulatory Peptides: From Molecular Biology to Function (Costa, E., and Trabucchi, M., Eds.), Raven Press, New York, pp. 413–422. [PubMed] [Google Scholar]
  57. Somogyi, P., Hodgson, A. J., Smith, A. D., Nunzi, M. G., Gorio, A., and Wu, J.-Y. (1984). Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin-or cholecystokinin-immunoreactive material.J. Neurosci.42590–2603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Srikant, C. B., and Patel, Y. C. (1981). Somatostatin receptors: Identification and chracterization in rat brain membranes.Proc. Natl. Acad. Sci.783930–3934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Sternberger, L. A. (1979).Immunocytochemistry, Wiley, New York. [Google Scholar]
  60. Tan, A. T., Tsang, D., Renaud, L. P., and Martin, J. B. (1977). Effect of somatostatin on calcium transport in guinea pig cortex synaptosomes.Brain Res.123193–196. [DOI] [PubMed] [Google Scholar]
  61. Tanaka, S., and Tsujimoto, A. (1981). Somatostatin facilitates the serotonin release from rat cerebral cortex, hippocampus, and hypothalamus slices.Brain Res.208219–222. [DOI] [PubMed] [Google Scholar]
  62. Tornquist, K., Uddman, R., Sundler, F., and Ehinger, B. (1982). Somatostatin and VIP neurons in the retinae of different species.Histochemistry76137–146. [DOI] [PubMed] [Google Scholar]

Articles from Cellular and Molecular Neurobiology are provided here courtesy of Springer

RESOURCES