Journal of Neural Transmission

, Volume 114, Issue 7, pp 893–898

Deficits in parvalbumin and calbindin immunoreactive cells in the hippocampus of isolation reared rats

  • M. K. Harte
  • S. B. Powell
  • N. R. Swerdlow
  • M. A. Geyer
  • G. P. Reynolds
Article

Summary

Post-mortem studies have provided evidence for abnormalities of the γ-aminobutyric acid (GABA)-ergic system in schizophrenia. The calcium-binding proteins (CBPs), parvalbumin (PV), calbindin (CB) and calretinin (CR) can be used as markers for specific subpopulations of GABAergic neurons in the brain.

Isolation rearing of rats is a non-pharmacological, non-lesion manipulation that leads to deficits in prepulse inhibition of the startle reflex (PPI) and other behavioural and neurochemical alterations reminiscent of schizophrenia.

Female rats were reared in social housing (groups of three) or singly for 11 weeks post weaning and PPI was measured. Brains were removed and hippocampal CBP – containing neurons determined following immunocytochemical staining.

Compared to socially housed rats, isolated rats exhibited PPI deficits and reductions in PV and CB-immunoreactive cells in the hippocampus, with no significant change in CR. These findings demonstrate selective abnormalities of sub-populations of GABAergic interneurons in the hippocampus of isolation reared rats, which resemble the neuronal deficits seen in this region in schizophrenia.

Keywords: Schizophrenia, isolation rearing, hippocampus, GABA, calcium binding proteins 

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References

  1. Abdul-Monim Z, Neill JC, Reynolds GP (2006) Sub-chronic psychotomimetic phencyclidine induces deficits in reversal learning and alterations in parvalbumin-immunoreactive expression in the rat. J Psychopharmacol [Epub ahead of print]Google Scholar
  2. Bakshi, VP, Swerdlow, NR, Braff, DL, Geyer, MA 1998Reversal of isolation rearing-induced deficits in prepulse inhibition by Seroquel and olanzapineBiol Psychiatry43436445PubMedCrossRefGoogle Scholar
  3. Beasley, CL, Reynolds, GP 1997Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenicsSchizophr Res24349355PubMedCrossRefGoogle Scholar
  4. Beasley, CL, Zhang, ZJ, Patten, I, Reynolds, GP 2002Selective deficits in prefrontal cortical GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteinsBiol Psychiatry52708715PubMedCrossRefGoogle Scholar
  5. Benes, FM 1999Evidence for altered trisynaptic circuitry in schizophrenic hippocampusBiol Psychiatry46589599PubMedCrossRefGoogle Scholar
  6. Benes, FM, Lange, N 2001Two-dimensional versus three-dimensional cell counting: a practical perspectiveTrends Neurosci241117PubMedCrossRefGoogle Scholar
  7. Benes, FM, Khan, Y, Vincent, SL, Wickramasinghe, R 1996Differences in the subregional and cellular distribution of GABAA receptor binding in the hippocampal formation of schizophrenic brainSynapse22338349PubMedCrossRefGoogle Scholar
  8. Benes, FM, Kwok, EW, Vincent, SL, Todtenkopf, MS 1998A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressivesBiol Psychiatry448897PubMedCrossRefGoogle Scholar
  9. Braff, DL, Stone, C, Callaway, E, Geyer, MA, Glick, I, Bali, L 1978Prestimulus effects on human startle reflex in normals and schizophrenicsPsychophysiology15339343PubMedCrossRefGoogle Scholar
  10. Braff, DL, Grillon, C, Geyer, MA 1992Gating and habituation of the startle reflex in schizophrenic patientsArch Gen Psychiatry49206215PubMedGoogle Scholar
  11. Braff, DL, Geyer, MA, Swerdlow, NR 2001Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studiesPsychopharmacology156234258PubMedCrossRefGoogle Scholar
  12. Cahir, M, Costello, I, King, DJ, Reynolds, GP 2005Chronic haloperidol or clozapine treatment does not alter parvalbumin immunoreactivity in the rat frontal cortex or hippocampusNeurosci Lett3735760PubMedCrossRefGoogle Scholar
  13. Caine, SB, Geyer, MA, Swerdlow, NR 1991Carbachol infusion into the dentate gyrus disrupts sensorimotor gating of startle in the ratPsychopharmacology105347354PubMedCrossRefGoogle Scholar
  14. Caine, SB, Geyer, MA, Swerdlow, NR 1992Hippocampal modulation of acoustic startle and prepulse inhibition in the ratPharmacol Biochem Behav4312011208PubMedCrossRefGoogle Scholar
  15. Cilia, J, Reavill, C, Hagan, JJ, Jones, DN 2001Long-term evaluation of isolation-rearing induced prepulse inhibition deficits in ratsPsychopharmacology (Berl)156327337CrossRefGoogle Scholar
  16. Cochran, SM, Kennedy, M, McKerchar, CE, Steward, LJ, Pratt, JA, Morris, BJ 2003Induction of metabolic hypofunction and neurochemical deficits after chronic intermittent exposure to phencyclidine: differential modulation by antipsychotic drugsNeuropsychopharmacology28265275PubMedCrossRefGoogle Scholar
  17. Cotter, D, Landau, S, Beasley, C, Stevenson, R, Chana, G, MacMillan, L, Everall, I 2002The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophreniaBiol Psychiatry57377386CrossRefGoogle Scholar
  18. Daviss, SR, Lewis, DA 1995Local circuit neurons of the prefrontal cortex in schizophrenia: selective increase in the density of calbindin-immunoreactive neuronsPsychiatry Res598196PubMedCrossRefGoogle Scholar
  19. Freund, TF, Buzsaki, G 1996Interneurons of the hippocampusHippocampus6347470PubMedCrossRefGoogle Scholar
  20. Geyer, MA, Swerdlow, NR 1998

    Measurement of startle response, prepulse inhibition, and habituation

    Crawley, JNGerfen, CRMcKay, RRogawski, MASibley, DRSkolnick, P eds. Current protocols in neuroscienceJ WileyNew York8.7.18.7.15
    Google Scholar
  21. Geyer, MA, Wilkinson, LS, Humby, T, Robbins, TW 1993Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophreniaBiol Psychiatry34361372PubMedCrossRefGoogle Scholar
  22. Graham, F 1975The more or less startling effects of weak prestimulationPsychophysiology12238248PubMedCrossRefGoogle Scholar
  23. Grateron, L, Cebada-Sanchez, S, Marcos, P, Mohedano-Moriano, A, Insausti, AM, Muñoz, M,  et al. 2003Postnatal development of calcium-binding proteins immunoreactivity (parvalbumin, calbindin, calretinin) in the human entorhinal cortexJ Chem Neuroanatom26311316CrossRefGoogle Scholar
  24. Greene, JRT, Kerkhoff, JE, Guiver, L, Totterdell, S 2001Structural and functional abnormalities of the hippocampal formation in rats with environmentally induced reductions in prepulse inhibition of acoustic startleNeuroscience103315323PubMedCrossRefGoogle Scholar
  25. Halasy, K, Miettinen, R, Szabat, E, Freund, TF 1992GABAergic interneurons are the major postsynaptic targets of median raphe afferents in the rat dentate gyrusEur J Neurosci4144153PubMedCrossRefGoogle Scholar
  26. Hall, FS, Wilkinson, LS, Humby, T, Inglis, W, Kendall, DA, Marsden, CA, Robbins, TW 1998Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systemsPharmacol Biochem Behav59859872PubMedCrossRefGoogle Scholar
  27. Heizmann, CW 1992Changes in Ca2+-binding proteins in human neurodegenerative disordersTrends Neurosci15259264PubMedCrossRefGoogle Scholar
  28. Iritani, S, Kuroki, N, Ikeda, K, Kazamatsuri, H 1999Calbindin immunoreactivity in the hippocampal formation and neocortex of schizophrenicsProg Neuropsychopharmacol23409421CrossRefGoogle Scholar
  29. Jones, GH, Hernandez, TD, Kendall, DA, Marsden, CA, Robbins, TW 1992Dopaminergic and serotonergic function following isolation-rearing in rats: A study of behavioural responses and post-mortem and in vivo neurochemistryPharmacol Biochem Behav431735PubMedCrossRefGoogle Scholar
  30. Koch, M 1999The neurobiology of startleProg Neurobiol59107128PubMedCrossRefGoogle Scholar
  31. Mansbach, RS, Geyer, MA, Braff, DL 1988Dopaminergic stimulation disrupts sensorimotor gating in the ratPsychopharmacology94507514PubMedCrossRefGoogle Scholar
  32. Paxinos, G, Watson, C 1998The rat brain in stereotaxic coordinates4Academic PressOrlando, FLGoogle Scholar
  33. Porebski, A, Buslei, R, Bayer, TA, Vogeley, K, Bogerts, B, Majtenyi, B, Honer, WG, Falkai, P 1999Analysis of the ratio of calretinin-expressing interneurons and pyramidal neurons in the hippocampus of patients with schizophreniaJ Neur Psychiatr Brain Res7143146Google Scholar
  34. Powell, SB, Swerdlow, NR, Pitcher, LK, Geyer, MA 2002Isolation rearing induced deficits in prepulse inhibition and locomotor habituation are not potentiated by water deprivationPhysiol Behav775564PubMedCrossRefGoogle Scholar
  35. Powell, SB, Geyer, MA, Preece, MA, Pitcher, LK, Reynolds, GP, Swerdlow, NR 2003Dopamine depletion of the nucleus accumbens reverses isolation-induced deficits in prepulse inhibition in ratsNeuroscience119233240PubMedCrossRefGoogle Scholar
  36. Reynolds, GP, Beasley, CL 2001GABAergic neuronal subtypes in human frontal cortex – development and deficits in schizophreniaJ Chem Neuroanat2295100PubMedCrossRefGoogle Scholar
  37. Reynolds, GP, Czudek, C, Andrews, HB 1990Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophreniaBiol Psychiatry2710381044PubMedCrossRefGoogle Scholar
  38. Ribak, CE, Nitsch, R, Seress, L 1990Proportion of parvalbumin-positive basket cells in the GABAergic innervation of pyramidal and granule cells of the rat hippocampal formationJ Compar Neurol300449461CrossRefGoogle Scholar
  39. Sahakian, BJ, Robbins, TW, Iversen, SD 1977The effects of isolation rearing on exploration in the ratAnim Learn Behav5193198Google Scholar
  40. Seress, L, Gulyás, I, Ferrer, T, Tunon, E, Soriano, Freund TF 1993Distribution, morphological features, and synaptic connections of parvalbumin-immunoreactive and calbindin-d(28k)-immunoreactive neurons in the human hippocampal formationJ Compar Neurol337208230CrossRefGoogle Scholar
  41. Solbach, S, Celio, MR 1991Ontogeny of the calcium binding protein parvalbumin in the rat nervous systemAnatom Embryol184103124CrossRefGoogle Scholar
  42. Swerdlow, NR, Caine, SB, Braff, DL, Geyer, MA 1992Neural substrates of sensorimotor gating of the startle reflex: preclinical findings and their implicationsJ Psychopharmacol6176190CrossRefGoogle Scholar
  43. Swerdlow, NR, Geyer, MA, Braff, DL 2001Neural circuit regulation of prepuolse inhibition of startle in the rat: current knowledge and future challengesPsychopharmacology156194215PubMedCrossRefGoogle Scholar
  44. Varty, GB, Higgins, GA 1995Examination of drug-induced and isolation-induced disruptions of prepulse inhibition as models to screen antipsychotic drugsPsychopharmacology1221526PubMedCrossRefGoogle Scholar
  45. Varty, GB, Marsden, CA, Higgins, GA 1999Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared ratsBrain Res824197203PubMedCrossRefGoogle Scholar
  46. Weiss, IC, Feldon, J 2001Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a reviewPsychopharmacology156305326PubMedCrossRefGoogle Scholar
  47. Wilkinson, LS, Killcross, SS, Humby, T, Hall, FS, Geyer, MA, Robbins, TW 1994Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibitionNeuropsychopharmacology106172PubMedGoogle Scholar
  48. Zhang, ZJ, Reynolds, GP 2002A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophreniaSchizophr Res55110PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • M. K. Harte
    • 1
  • S. B. Powell
    • 2
  • N. R. Swerdlow
    • 2
  • M. A. Geyer
    • 2
  • G. P. Reynolds
    • 1
  1. 1.Division of Psychiatry and NeuroscienceWhitla Medical Building, Queen’s UniversityBelfastU.K.
  2. 2.Department of PsychiatryUniversity of CaliforniaSan Diego, La JollaU.S.A.

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