Skip to main content
PMC home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2009 Oct 7;25(5):309. doi: 10.1007/s12264-009-0831-5

Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices: Multi-electrode array recordings

长串与短串θ节律刺激在大鼠前扣带回皮质脑片诱导长时程增强效应的不同作用: 平面微电极阵列记录技术

Ying He 1, Ming-Gang Liu 1, Ke-Rui Gong 1, Jun Chen 1,2,✉
PMCID: PMC5552605  PMID: 19784087

Abstract

Objective

There is substantial evidence supporting the notion that the anterior cingulate cortex (ACC) is an important limbic structure involved in multiple brain functions such as sensory perception, motor conflict monitoring, memory, emotion and cognition. It has been shown that long term potentiation (LTP) is an important synaptic model of neural plasticity in the ACC, however, little is known about the spatiotemporal properties of ACC at network level. The present study was designed to see the LTP induction effects across different layers of the ACC by using different conditioning stimuli (CS) protocols.

Methods

A unique multi-electrode array recording technique was used in the acutely-dissociated ACC slices of rats. Long and short train theta burst stimulation (TBS) paradigms were applied in layer V–VI as the CS and the LTP induction effects were compared across different layers of the ACC. Briefly, both long and short train TBS are composed of bursts (4 pulses at 100 Hz) with a 200 ms interval, however, the former (TBS1) was with 10 trains and the latter (TBS2) was with 5 trains. After test stimulation at layer V–VI in the ACC, network field potentials (FPs) could be simultaneously recorded across all layers of the ACC.

Results

The waveforms of FPs were different across different layers. Namely, positive-going waveforms were recorded in layer I and negative-going waveforms were recorded in layers V–VI, in contrast, complex waveforms were localized mainly in layers II–III. Following application of two CS protocols, the induction rate of LTP was significantly different between TBS1 and TBS2 regardless of the spatial properties. TBS1 had more than 60% success, while TBS2 was less than 25% in induction of LTP. Moreover, both the 2 CS protocols could induce LTP in layers II–III and layers V–VI without layer-related difference. However, no LTP was inducible in layer I.

Conclusion

The present findings indicate that stimulation protocols may, at least in part, account for a large portion of variations among previous LTP studies, and hence highlight the importance of selecting the best LTP induction protocol when designing such experiments. Moreover, the present results demonstrate the prominent superiority of multi-electrode array recording in revealing the network properties of synaptic activities in the ACC, especially in comparing the spatiotemporal characteristics between different layers of this structure.

Key words: long term potentiation, anterior cingulate cortex, theta burst stimulation, multi-electrode array recordings, rat

References

  • [1].Devinsky O., Morrell M.J., Vogt B.A. Contributions of anterior cingulate cortex to behavior. Brain. 1995;118:279–306. doi: 10.1093/brain/118.1.279. [DOI] [PubMed] [Google Scholar]
  • [2].Zhuo M. A synaptic model for pain: long-term potentiation in the anterior cingulate cortex. Mol Cells. 2007;23:259–271. [PubMed] [Google Scholar]
  • [3].Condé F., Audinat E., Maire-Lepoivre E., Crépel F. Afferent connections of the medial frontal cortex of the rat. A study using retrograde transport of fluorescent dyes. I. Thalamic afferents. Brain Res Bull. 1990;24:341–354. doi: 10.1016/0361-9230(90)90088-H. [DOI] [PubMed] [Google Scholar]
  • [4].Pandya D.N., Van Hoesen G.W., Mesulam M.M. Efferent connections of the cingulate gyrus in the rhesus monkey. Exp Brain Res. 1981;42:319–330. doi: 10.1007/BF00237497. [DOI] [PubMed] [Google Scholar]
  • [5].Wang C.C., Shyu B.C. Differential projections from the mediodorsal and centrolateral thalamic nuclei to the frontal cortex in rats. Brain Res. 2004;995:226–235. doi: 10.1016/j.brainres.2003.10.006. [DOI] [PubMed] [Google Scholar]
  • [6].Vogt B.A. Pain and emotion interactions in subregions of the cingulate gyrus. Nat Neurosci. 2005;6:533–544. doi: 10.1038/nrn1704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Zhuo M. Cortical excitation and chronic pain. Trends Neurosci. 2008;31:199–207. doi: 10.1016/j.tins.2008.01.003. [DOI] [PubMed] [Google Scholar]
  • [8].Johansen J.P., Fields H.L. Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal. Nat Neurosci. 2004;7:398–403. doi: 10.1038/nn1207. [DOI] [PubMed] [Google Scholar]
  • [9].Tang J., Ko S., Ding H.K., Qiu C.S., Calejesan A.A., Zhuo M. Pavlovian fear memory induced by activation in the anterior cingulate cortex. Mol Pain. 2005;1:6. doi: 10.1186/1744-8069-1-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Pastoriza L.N., Morrow T.J., Casey K.L. Medial frontal cortex lesions selectively attenuate the hot plate response: possible nocifensive apraxia in the rat. Pain. 1996;64:11–17. doi: 10.1016/0304-3959(95)00070-4. [DOI] [PubMed] [Google Scholar]
  • [11].Ren L.Y., Lu Z.M., Liu M.G., Yu Y.Q., Li Z., Shang G.W., Chen J. Distinct roles of the anterior cingulate cortex in spinal and supraspinal bee venom-induced pain behaviors. Neuroscience. 2008;153:268–278. doi: 10.1016/j.neuroscience.2008.01.067. [DOI] [PubMed] [Google Scholar]
  • [12].Johansen J.P., Fields H.L., Manning B.H. The affective component of pain in rodents: direct evidence for a contribution of the anterior cingulate cortex. Proc Natl Acad Sci USA. 2001;98:8077–8082. doi: 10.1073/pnas.141218998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13].Casey K.L. Forebrain mechanisms of nociception and pain: analysis through imaging. Proc Natl Acad Sci USA. 1999;96:7668–7674. doi: 10.1073/pnas.96.14.7668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Hutchison W.D., Davis K.D., Lozano A.M., Tasker R.R., Dostrovsky J.O. Pain-related neurons in the human cingulate cortex. Nat Neurosci. 1999;2:403–405. doi: 10.1038/8065. [DOI] [PubMed] [Google Scholar]
  • [15].Rainville P., Duncan G.H., Price D.D., Carrier B., Bushnell M.C. Pain affect encoded in human anterior cingulate but not somatosen-sory cortex. Science. 1997;277:968–971. doi: 10.1126/science.277.5328.968. [DOI] [PubMed] [Google Scholar]
  • [16].Sikes R.W., Vogt B.A. Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol. 1992;68:1720–1732. doi: 10.1152/jn.1992.68.5.1720. [DOI] [PubMed] [Google Scholar]
  • [17].Talbot J.D., Marrett S., Evans A.C., Meyer E., Bushnell M.C., Duncan G.H. Multiple representations of pain in human cerebral cortex. Science. 1991;251:1355–1358. doi: 10.1126/science.2003220. [DOI] [PubMed] [Google Scholar]
  • [18].Vogt B.A., Derbyshire S., Jones A.K. Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging. Eur J Neurosci. 1996;8:1461–1473. doi: 10.1111/j.1460-9568.1996.tb01608.x. [DOI] [PubMed] [Google Scholar]
  • [19].Zhuo M. Molecular mechanisms of pain in the anterior cingulate cortex. J Neurosci Res. 2006;84:927–933. doi: 10.1002/jnr.21003. [DOI] [PubMed] [Google Scholar]
  • [20].Zhuo M. Targeting central plasticity: a new direction of finding painkillers. Curr Pharm Des. 2005;11:2797–2807. doi: 10.2174/1381612054546798. [DOI] [PubMed] [Google Scholar]
  • [21].Bliss T.V.P., Collingridge G.L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361:31–39. doi: 10.1038/361031a0. [DOI] [PubMed] [Google Scholar]
  • [22].Malenka R.C., Nicoll R.A. LTP-A decade of progress? Science. 1999;85:1870–1874. doi: 10.1126/science.285.5435.1870. [DOI] [PubMed] [Google Scholar]
  • [23].Wei F., Qiu C.S., Liauw J., Robinson D.A., Ho N., Chatila T., et al. Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat Neurosci. 2002;5:573–579. doi: 10.1038/nn0602-855. [DOI] [PubMed] [Google Scholar]
  • [24].Zhao M.G., Toyoda H., Lee Y.S., Wu L.J., Ko S.W., Zhang X.H., et al. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron. 2005;47:859–872. doi: 10.1016/j.neuron.2005.08.014. [DOI] [PubMed] [Google Scholar]
  • [25].Wei F., Xia X.M., Tang J., Ao H., Ko S., Liauw J., et al. Calmodulin regulates synaptic plasticity in the anterior cingulate cortex and behavioral responses: a microelectroporation study in adult rodents. J Neurosci. 2003;23:8402–8409. doi: 10.1523/JNEUROSCI.23-23-08402.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Sah P., Nicoll R.A. Mechanisms underlying potentiation of synaptic transmission in rat anterior cingulate cortex in vitro. J Physiol. 1991;433:615–630. doi: 10.1113/jphysiol.1991.sp018446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Toyoda H., Zhao M.G., Xu H., Wu L.J., Ren M., Zhuo M. Requirement of extracellular signal-regulated kinase/mitogen-activated protein kinase for long-term potentiation in adult mouse anterior cingulate cortex. Mol Pain. 2007;3:36. doi: 10.1186/1744-8069-3-36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28].Zhao M.G., Toyoda H., Ko S.W., Ding H.K., Wu L.J., Zhuo M. Deficits in trace fear memory and long-term potentiation in a mouse model for fragile X syndrome. J Neurosci. 2005;25:7385–7392. doi: 10.1523/JNEUROSCI.1520-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [29].Wu L.J., Zhang X.H., Fukushima H., Zhang F., Wang H., Toyoda H., et al. Genetic enhancement of trace fear memory and cingulate potentiation in mice overexpressing Ca2+/calmodulin-dependent protein kinase IV. Eur J Neurosci. 2008;27:1923–1932. doi: 10.1111/j.1460-9568.2008.06183.x. [DOI] [PubMed] [Google Scholar]
  • [30].Albensi B.C., Oliver D.R., Toupin J., Odero G. Electrical stimulation protocols for hippocampal synaptic plasticity and neuronal hyper-excitability: are they effective or relevant? Exp Neurol. 2007;204:1–13. doi: 10.1016/j.expneurol.2006.12.009. [DOI] [PubMed] [Google Scholar]
  • [31].Hernandez R.V., Navarro M.M., Rodriguez W.A., Martinez J.L., Jr, LeBaron R.G. Differences in the magnitude of long-term potentiation produced by theta burst and high frequency stimulation protocols matched in stimulus number. Brain Res Protoc. 2005;15:6–13. doi: 10.1016/j.brainresprot.2005.02.003. [DOI] [PubMed] [Google Scholar]
  • [32].Gabbott P.L., Dickie B.G., Vaid R.R., Headlam A.J., Bacon S.J. Localcircuit neurones in the medial prefrontal cortex (areas 25, 32 and 24b) in the rat: morphology and quantitative distribution. J Comp Neurol. 1997;377:465–499. doi: 10.1002/(SICI)1096-9861(19970127)377:4<465::AID-CNE1>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  • [33].Vogt B.A., Vogt L., Farber N.B., Bush G. Architecture and neurocytology of monkey cingulate gyrus. J Comp Neurol. 2005;485:218–239. doi: 10.1002/cne.20512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [34].Oka H., Shimono K., Ogawa R., Sugihara H., Taketani M. A new planar multielectrode array for extracellular recording: application to hippocampal acute slice. J Neurosci Methods. 1999;93:61–67. doi: 10.1016/S0165-0270(99)00113-2. [DOI] [PubMed] [Google Scholar]
  • [35].Shimono K., Brucher F., Granger R., Lynch G., Taketani M. Origins and distribution of cholinergically induced β rhythms in hippocampal slices. J Neurosci. 2000;20:8462–8473. doi: 10.1523/JNEUROSCI.20-22-08462.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Shimono K., Kubota D., Brucher F., Taketani M., Lynch G. Asymmetrical distribution of the Schaffer projections within the apical dendrites of hippocampal field CA1. Brain Res. 2002;950:279–287. doi: 10.1016/S0006-8993(02)03052-4. [DOI] [PubMed] [Google Scholar]
  • [37].Krause M., Jia Y. Serotonergic modulation of carbachol-induced rhythmic activity in hippocampal slices. Neuropharmacology. 2005;48:381–390. doi: 10.1016/j.neuropharm.2004.10.011. [DOI] [PubMed] [Google Scholar]
  • [38].Duport S., Millerin C., Muller D., Corrèges P. A metallic multisite recording system designed for continuous long-term monitoring of electrophysiological activity in slice cultures. Biosens Bioelectron. 1999;14:369–376. doi: 10.1016/S0956-5663(99)00015-9. [DOI] [PubMed] [Google Scholar]
  • [39].Hofmann F., Bading H. Long term recordings with microelectrode arrays: studies of transcription-dependent neuronal plasticity and axonal regeneration. J Physiol (Paris) 2006;99:125–132. doi: 10.1016/j.jphysparis.2005.12.005. [DOI] [PubMed] [Google Scholar]
  • [40].Morin F.O., Takamura Y., Tamiya E. Investigating neuronal activity with planar microelectrode arrays: achievements and new perspectives. J Biosci Bioeng. 2005;100:131–143. doi: 10.1263/jbb.100.131. [DOI] [PubMed] [Google Scholar]
  • [41].Steidl E.M., Neveu E., Bertrand D., Buisson B. The adult rat hippocampal slice revisited with multi-electrode arrays. Brain Res. 2006;1096:70–84. doi: 10.1016/j.brainres.2006.04.034. [DOI] [PubMed] [Google Scholar]
  • [42].Colgin L.L. Investigation of network phenomena in hippocampal slices using multi-electrode recording arrays. In: Taketani M., Baudry M., editors. Advances in network electrophysiology using multi-electrode arrays. Singapore: Springer; 2006. pp. 425–453. [Google Scholar]
  • [43].van Bergen A., Papanikolaou T., Schuker A., Möller A., Schlosshauer B. Long-term stimulation of mouse hippocampal slice culture on microelectrode array. Brain Res Protoc. 2003;11:123–133. doi: 10.1016/S1385-299X(03)00024-2. [DOI] [PubMed] [Google Scholar]
  • [44].Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16:109–110. doi: 10.1016/0304-3959(83)90201-4. [DOI] [PubMed] [Google Scholar]
  • [45].Paxinos G., Watson C.R. The Rat Brain in Stererotaxic Coordinates. 5. Amsterdam: Elsevier Academic Press; 2005. p. 367. [Google Scholar]
  • [46].Yamamura H., Iwata K., Tsuboi Y., Toda K., Kitajima K., Shimizu N., et al. Morphological and electrophysiological properties of ACCx nociceptive neurons in rats. Brain Res. 1996;735:83–92. doi: 10.1016/0006-8993(96)00561-6. [DOI] [PubMed] [Google Scholar]
  • [47].Larson J., Wong D., Lynch G. Patterned stimulation at the theta frequency is optimal for the induction of hippocampal longterm potentiation. Brain Res. 1986;368:347–350. doi: 10.1016/0006-8993(86)90579-2. [DOI] [PubMed] [Google Scholar]
  • [48].Staubli U., Lynch G. Stable hippocampal long-term potentiation elicited by ‘theta’ pattern stimulation. Brain Res. 1987;435:227–234. doi: 10.1016/0006-8993(87)91605-2. [DOI] [PubMed] [Google Scholar]
  • [49].Zhang X.H., Wu L.J., Gong B., Ren M., Li B.M., Zhuo M. Inductionand conditioning-protocol dependent involvement of NR2Bcontaining NMDA receptors in synaptic potentiation and contextual fear memory in the hippocampal CA1 region of rats. Mol Brain. 2008;1:9. doi: 10.1186/1756-6606-1-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [50].Ko S.W., Vadakkan K.I., Ao H., Gallitano-Mendel A., Wei F., Milbrandt J., et al. Selective contribution of Egr1 (zif/268) to persistent inflammatory pain. J Pain. 2005;6:12–20. doi: 10.1016/j.jpain.2004.10.001. [DOI] [PubMed] [Google Scholar]
  • [51].Liauw J., Wu L.J., Zhuo M. Calcium-stimulated adenylyl cyclases required for long-term potentiation in the anterior cingulate cortex. J Neurophysiol. 2005;94:878–882. doi: 10.1152/jn.01205.2004. [DOI] [PubMed] [Google Scholar]
  • [52].Ji R.R., Kohno T., Moore K.A., Woolf C.J. Central sensitization and LTP do pain and memory share similar mechanisms. Trends Neurosci. 2003;26:696–705. doi: 10.1016/j.tins.2003.09.017. [DOI] [PubMed] [Google Scholar]
  • [53].Sandkühler J. Learning and memory in pain pathways. Pain. 2000;88:113–118. doi: 10.1016/S0304-3959(00)00424-3. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES