Skip to main content
Log in

Stimulus-dependent, reciprocal up- and downregulation of glutamic acid decarboxylase and Ca2+/calmodulin-dependent protein kinase II gene expression in rat cerebral cortex

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Long-train tetanic stimulation of the cerebral cortex induces long-term changes in the excitability of cortical neurons, while short-train electrical stimulation does not. In the present study, we show that both forms of stimulation when applied to rat motor cortex for 4 h enhance c-fos expression, but only tetanic stimulation, when imposed upon short-train stimulation, modulates gene expression for 67-kDa glutamic acid decarboxylase (GAD) and alpha Ca2+/calmodulin-dependent protein kinase II (CaMKIIα). Gene expression for beta Ca2+/calmodulin-dependent protein kinase II is not affected by either stimulation mode. GAD messenger RNA (mRNA) is increased from 1 h after the end of tetanization to the longest poststimulus survival time investigated (14 h). CaMKIIα mRNA is decreased 1–3 h after the end of tetanization but thereafter returns to prestimulus levels. These results imply not only that mechanisms underlying neocortical plasticity are stimulus-dependent but also that they involve reciprocal changes in molecules regulating the balance of excitation and inhibition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adamec RE (1991) Partial kindling of the ventral hippocampus: identification of changes in limbic physiology which accompany changes in feline aggression and defense. Physiol Behav 49:443–453

    Google Scholar 

  • Asanuma H, Sakata H (1967) Functional organization of a cortical efferent system examined with focal depth stimulation in cats. J Neurophysiol 30:35–54

    Google Scholar 

  • Ascher P, Nowak L (1988) The role of divalent cations in the N- methyl-d-aspartate responses of mouse central neurons in culture. J Physiol (Lond) 399:247–266

    Google Scholar 

  • Ballarín M, Ernfors P, Lindefors N, Persson H (1991) Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain. Exp Neurol 114:35–43

    Google Scholar 

  • Bennett MK, Kennedy MB (1987) Deduced primary structure of the β subunit of brain type II Ca2+/calmodulin-dependent protein kinase determined by molecular cloning. Proc Natl Acad Sci USA 84:1794–1798

    Google Scholar 

  • Benson DL, Isackson PJ, Gall CM, Jones EG (1991a) Differential effects of monocular deprivation on glutamic acid decarboxylase and type II calcium-calmodulin-dependent protein kinase gene expression in the adult monkey visual cortex. J Neurosci 11:31–47

    Google Scholar 

  • Benson DL, Isackson PJ, Hendry SHC, Jones EG (1991b) Differential gene expression for glutamic acid decarboxylase and type II calcium-calmodulin-dependent protein kinase in basal ganglia, thalamus, and hypothalamus of the monkey. J Neurosci 11:1540–1564

    Google Scholar 

  • Benson DL, Isackson PJ, Gall CM, Jones EG (1992) Contrasting patterns in the localization of glutamic acid decarboxylase and Ca2+/calmodulin protein kinase gene expression in the rat central nervous system. Neuroscience 46:825–849

    Google Scholar 

  • Benson DL, Huntsman MM, Jones EG (1994) Activity-dependent changes in GAD and preprotachykinin mRNAs in visual cortex of adult monkeys. Cereb Cortex 4:40–51

    Google Scholar 

  • Berry RL, Teyler TJ, Taizhen H (1989) Induction of LTP in rat primary visual cortex: tetanus parameters. Brain Res 481:221–227

    Google Scholar 

  • Bindman LJ, Murphy KPSJ (1990) Delayed onset of potentiation in neocortical EPSPs during long-term potentiation (LTP) — a postsynaptic mechanism or heterogeneous synaptic inputs? Adv Exp Med Biol 268:307–312

    Google Scholar 

  • Bindman LJ, Murphy KPSJ, Pockett S (1988) Postsynaptic control of the induction of long-term changes in efficacy of transmission at neocortical synapses in slices of rat brain. J Neurophysiol 60:1053–1065

    Google Scholar 

  • Bliss TVP, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  CAS  PubMed  Google Scholar 

  • Bronstein JM, Farber DB, Micevych PE, Lasher R, Wasterlain CG (1990) Kindling induced changes in calmodulin kinase II immunoreactivity. Brain Res 524:49–53

    Google Scholar 

  • Bronstein JM, Micevich P, Popper P, Huez G, Farber DB, Wasterlain CG (1992) Long-lasting decreases of type II calmodulin kinase expression in kindled rat brains. Brain Res 584: 257–260

    Google Scholar 

  • Bronstein JM, Farber DB, Wasterlain CG (1993) Regulation of type-II calmodulin kinase: functional implications. Brain Res Brain Res Rev 18:135–147

    Google Scholar 

  • Cole AJ, Saffen DW, Baraban JM, Worley PF (1989) Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 340:474–476

    Google Scholar 

  • Collingridge GL, Herron CE, Lester RA (1988) Frequency-dependent N-methyl-d-aspartate receptor-mediated synaptic transmission in rat hippocampus. J Physiol (Lond) 399:301–312

    Google Scholar 

  • Davies CH, Starkey SJ, Pozza MF, Collingridge GL (1991) GABAB autoreceptors regulate the induction of LTP. Nature 349:609–611

    Google Scholar 

  • Dawson TM, Snyder SH (1994) Gases as biological messengers: nitric oxide and carbob monoxide in the brain. J Neurosci 14: 5147–5159

    Google Scholar 

  • Demmer J, Dragunow M, Lawlor PA, Mason SE, Leah JD, Abraham WC, Tate WP (1993) Differential expression of immediate early genes after hippocampal long-term potentiation in awake rats. Brain Res Mol Brain Res 17:279–286

    Google Scholar 

  • Donoghue JP, Wise SP (1982) The motor cortex of the rat: cytoarchitecture and microstimulation mapping. J Comp Neurol 212:76–82

    Google Scholar 

  • Dragunow M, Faull R (1989) The use of c-fos as a metabolic marker in neuronal pathway tracing. J Neurosci Methods 29:261–265

    Google Scholar 

  • Fukunaga K, Stoppini L, Miyamoto E, Muller D (1993) Long-term potentiation is associated with a increased activity of Ca2+/calmodulin-dependent protein kinase II. J Biol Chem 268:7863–7867

    Google Scholar 

  • Grant SGN, Silva AJ (1994) Targeting learning. Trends Neurosci 17:71–75

    Google Scholar 

  • Hall RD, Lindholm EP (1974) Organization of motor and somato-sensory neocortex in the albino rat. Brain Res 66:23–38

    Google Scholar 

  • Hendry SHC, Jones EG (1986) Reduction in number of GABA immunostained neurons in deprived-eye dominance columns in area 17. Nature 320:750–753

    Google Scholar 

  • Hendry SHC, Jones EG (1988) Activity dependent regulation of GABA expression in the visual cortex of adult monkeys. Neuron 1:701–712

    Google Scholar 

  • Hendry SHC, Kennedy MB (1986) Immunoreactivity for a calmodulin-dependent protein kinase is selectively increased in macaque striate cortex after monocular deprivation. Proc Natl Acad Sci USA 83:1536–1540

    Google Scholar 

  • Hess G, Donoghue JP (1994) Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical motor maps. J Neurophysiol 71:2543–2547

    Google Scholar 

  • Honkaniemi J, Sagar SM, Pyykönen I, Hicks KJ, Sharp FR (1995) Focal brain injury induces multiple immediate early genes encoding zinc finger transcription factors. Brain Res Mol Brain Res 28:157–163

    Article  CAS  PubMed  Google Scholar 

  • Iriki A, Pavlides C, Keller A, Asanuma H (1991) Long-term potentiation of thalamic input to the motor cortex induced by co-activation of thalamocortical and corticocortical afferents. J Neurophysiol 65:1435–1441

    Google Scholar 

  • Jeffery KJ, Abraham WC, Dragunow M, Mason SE (1990) Induction of fos-like immunoreactivity and the maintenance of long-term potentiation in the dentate gyrus of unanesthetized rats. Brain Res Mol Brain Res 8:267–274

    Google Scholar 

  • Jones EG (1993) GABAergic neurons and their role in cortical plasticity in primates. Cereb Cortex 3:361–372

    Google Scholar 

  • Jones EG, Huntley GW, Benson DL (1994) Alpha calcium/calmodulin-dependent protein kinase II selectively expressed in a subpopulation of excitatory neurons in monkey sensory-motor cortex: comparison with GAD-67 expression. J Neurosci 14: 611–629

    Google Scholar 

  • Keller A, Iriki A, Asanuma H (1990) Identification of neurons producing long-term potentiation in the cat motor cortex: intracellular recordings and labeling. J Comp Neurol 300:47–60

    Google Scholar 

  • Keller A, Miyashita E, Asanuma H (1991) Minimal stimulus parameters and the effects of hyperpolarization on the induction of long-term potentiation in the cat motor cortex. Exp Brain Res 87:295–302

    Google Scholar 

  • Komatsu Y, Fujii K, Maeda J, Sakaguchi H (1988) Long-term potentiation of synaptic transmission in kitten visual cortex. J Neurophysiol 59:124–141

    Google Scholar 

  • Liang F, Rouiller EM, Wiesendanger M (1993) Modulation of sustained electromyographic activity by single intracortical microstimuli: comparison of two forelimb motor cortical areas of the rat. Somatosens Mot Res 10:51–61

    Google Scholar 

  • Mackler SA, Brooks BP, Eberwine JH (1992) Stimulus-induced coordinate changes in mRNA abundance in single postsynaptic hippocampal CA1 neurons. Neuron 9:539–548

    Google Scholar 

  • Malenka RC (1994) Synaptic plasticity in the hippocampus: LTP and LTD. Cell 78:535–538

    Google Scholar 

  • Malenka RC, Kauer JA, Perkel DJ, Mauk MD, Kelly PT, Nicoll RA, Waxham MN (1989) An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation. Nature 340:554–557

    Google Scholar 

  • Malinow R, Madison DV, Tsien R (1988) Persistent protein kinase activity underlying long-term potentiation. Nature 335:820–824

    Google Scholar 

  • Malinow R, Schulman H, Tsien RW (1989) Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. Science 245:862–866

    Google Scholar 

  • Mayer ML, Westbrook GL (1985) The action of N-methyl-d-aspartic acid on mouse spinal neurons in culture. J Physiol (Lond) 361:65–90

    Google Scholar 

  • McGuinness TL, Lai Y, Greengard P (1985) Ca2+/calmodulin-dependent protein kinase II. Isozymic forms from rat forebrain and cerebellum. J Biol Chem 260:1696–1704

    Google Scholar 

  • Merlin LR, Wong RK (1993) Synaptic modifications accompanying epileptogenesis in vitro: long-term depression of GABA-mediated inhibition. Brain Res 627:330–340

    Google Scholar 

  • Miller SG, Kennedy MB (1985) Distinct forebrain and cerebellar isozymes of type II Ca2+/calmodulin-dependent protein kinase associate differently with the postsynaptic density fraction. J Biol Chem 260:9039–9046

    Google Scholar 

  • Morgan JI, Curran T (1991) Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci 14:421–451

    Google Scholar 

  • Murray KD, Gall CM, Benson DL, Jones EG, Isackson PJ (1995) Decreased expression of the alpha subunit of Ca2+/calmodulin-dependent protein kinase type II mRNA in the adult rat CNS following recurrent limbic seizures. Brain Res Mol Brain Res 32:221–232

    Google Scholar 

  • Neafsey EJ, Sievert C (1982) A second forelimb motor area exists in rat frontal cortex. Brain Res 232:151–156

    Google Scholar 

  • Neafsey EJ, Bold EL, Haas G, Hurley-Gius KM, Quirk G, Sievert CF, Terreberry RR (1986) The organization of the rat motor cortex: a microstimulation mapping study. Brain Res Brain Res Rev 11:77–96

    Google Scholar 

  • Perlin JB, Churn SB, Lothman EW, DeLorenzo RJ (1992) Loss of type II calcium/calmodulin-dependent kinase activity correlates with stages of development of electrographic seizures in status epilepticus in rat. Epilepsy Res 11:111–118

    Google Scholar 

  • Rajsman G (1994) Plasticity of adult central fibre tracts. Prog Brain Res 100:195–201

    Google Scholar 

  • Richardson CL, Tate WE, Mason SE, Lawlor PA, Dragunow M, Abraham WC (1992) Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus. Brain Res 580:147–154

    Google Scholar 

  • Rouiller EM, Moret V, Liang F (1993) Comparison of the connectional properties of the two forelimb areas of the rat sensorimotor cortex: support for the presence of a premotor or supplementary motor cortical area. Somatosens Mot Res 10:269–289

    Google Scholar 

  • Sakamoto T, Porter LL, Asanuma H (1987) Long lasting potentiation of synaptic potentials in the motor cortex produced by stimulation of the sensory cortex in the cat: a basis of motor learning. Brain Res 413:360–364

    Google Scholar 

  • Schulman H, Hanson PI (1993) Multifunctional Ca2+/calmodulin-dependent protein kinase. Neurochem Res 18:65–77

    Google Scholar 

  • Schuman EM, Madison DV (1994) Nitric oxide and synaptic function. Annu Rev Neurosci 17:153–183

    Google Scholar 

  • Sharp JW, Sagar SM, Hisanaga K, Jasper P, Sharp FR (1990) The NMDA receptor mediates cortical induction of fos and fos related antigens following cortical injury. Exp Neurol 109:323–332

    Google Scholar 

  • Shaw CA, Lanius RA, Doel K van den (1994) The origin of synaptic plasticity: crucial molecules or a dynamical cascade? Brain Res Brain Res Rev 19:241–263

    Google Scholar 

  • Sheng M, Greenberg ME (1990) The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron 4:477–485

    Google Scholar 

  • Silva AJ, Giese KP (1994) Plastic genes are in! Curr Opin Neurobiol 4:413–420

    Google Scholar 

  • Soderling TR (1993) Calcium/calmodulin-dependent protein kinase II: role in learning and memory. Mol Cell Biochem 127/128:93–101

    Google Scholar 

  • Weiler IJ, Wang X, Greenough WT (1994) Synapse-activated protein synthesis as a possible mechanism of plastic neural change. Prog Brain Res 100:189–194

    Google Scholar 

  • Wisden W, Errington ML, Williams S, Dunnett SB, Waters C, Hitchcock D, Evan G, Bliss TV, Hunt SP (1990) Differential expression of immediate early genes in the hippocampus and spinal cord. Neuron 4:603–614

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liang, F., Isackson, P.J. & Jones, E.G. Stimulus-dependent, reciprocal up- and downregulation of glutamic acid decarboxylase and Ca2+/calmodulin-dependent protein kinase II gene expression in rat cerebral cortex. Exp Brain Res 110, 163–174 (1996). https://doi.org/10.1007/BF00228548

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00228548

Key words

Navigation