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Theta synchronization between the hippocampus and the nucleus incertus in urethane-anesthetized rats

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Abstract

Oscillatory coupling between distributed areas can constitute a mechanism for neuronal integration. Theta oscillations provide temporal windows for hippocampal processing and only appear during certain active states of animals. Since previous studies have demonstrated that nucleus incertus (NI) contributes to the generation of hippocampal theta activity, in this paper, we evaluated the oscillatory coupling between both structures. We compared hippocampal and NI field potentials that were simultaneously recorded in urethane-anesthetized rats. Electrical and cholinergic stimulations of the reticularis pontis oralis nucleus have been used as hippocampal theta generation models. The spectral analyses reveal that electrical stimulation induced an increase in theta oscillations in both channels, whose frequencies depended on the intensity of stimulation. The intensity range used simultaneously increased the normalized spectral energy in the fast theta band (6–12 Hz) in HPC and NI. Frequencies within the theta range were found to be very similar in both channels. In order to validate coupling, spectral coherence was inspected. The data reveal that coherence in the high theta band also increased while stimuli were applied. Cholinergic activation progressively increased the main frequency in both structures to reach an asymptotic period with stable peak frequency in the low theta range (3–6 Hz), which could be first observed in NI and lasted about 1,500 s. Coherence in this band reached values close to 1. Taken together, these results support an electrophysiological and functional coupling between the hippocampus and the reticular formation, suggesting NI to be part of a distributed network working at theta frequencies.

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References

  • Alonso A, García-Austt E (1987a) Neuronal sources of theta rhythm in the entorhinal cortex of the rat. I. Laminar distribution of theta field potentials. Exp Brain Res 67:493–501

    Article  PubMed  CAS  Google Scholar 

  • Alonso A, García-Austt E (1987b) Neuronal sources of theta rhythm in the entorhinal cortex of the rat. II. Phase relations between unit discharges and theta field potentials. Exp Brain Res 67:502–509

    Article  PubMed  CAS  Google Scholar 

  • Alonso JR, U HS, Amaral DG (1996) Cholinergic innervation of the primate hippocampal formation: II. Effects of fimbria/fornix transection. J Comp Neurol 375:527–551

    Article  PubMed  CAS  Google Scholar 

  • Bassant MH, Poindessous-Jazat F (2001) Ventral tegmental nucleus of Gudden: a pontine hippocampal theta generator? Hippocampus 11:809–813

    Article  PubMed  CAS  Google Scholar 

  • Berman A (1968) The brain stem of the cat: a cytoarchitectonic atlas with stereotaxic coordinates. University of Wisconsin Press, Madison

    Google Scholar 

  • Bland BH (1986) The physiology and pharmacology of hippocampal formation theta rhythms. Prog Neurobiol 26:1–54

    Article  PubMed  CAS  Google Scholar 

  • Bland BH, Colom LV (1993) Extrinsic and intrinsic properties underlying oscillation and synchrony in limbic cortex. Prog Neurobiol 41:157–208

    Article  PubMed  CAS  Google Scholar 

  • Bland BH, Oddie SD (1998) Anatomical, electrophysiological and pharmacological studies of ascending brainstem hippocampal synchronizing pathways. Neurosci Biobehav Rev 22:259–273

    Article  PubMed  CAS  Google Scholar 

  • Bland BH, Oddie SD (2001) Theta band oscillation and synchrony in the hippocampal formation and associated structures: the case for its role in sensorimotor integration. Behav Brain Res 127:119–136

    Article  PubMed  CAS  Google Scholar 

  • Burazin TCD, Bathgate RAD, Macris M, Layfield S, Gundlach AL, Tregear GW (2002) Restricted, but abundant, expression of the novel rat gene-3 (R3) relaxin in the dorsal tegmental region of brain. J Neurochem 82:1553–1557

    Article  PubMed  CAS  Google Scholar 

  • Buzsáki G (1989) Two-stage model of memory trace formation: a role for “noisy” brain states. Neuroscience 31:551–570

    Article  PubMed  Google Scholar 

  • Buzsáki G (2002) Theta oscillations in the hippocampus. Neuron 33:325–340

    Article  PubMed  Google Scholar 

  • Chrobak JJ, Lörincz A, Buzsáki G (2000) Physiological patterns in the hippocampo-entorhinal cortex system. Hippocampus 10:457–465

    Article  PubMed  CAS  Google Scholar 

  • Colgin LL, Moser EI (2009) Hippocampal theta rhythms follow the beat of their own drum. Nat Neurosci 12:1483–1484

    Article  PubMed  CAS  Google Scholar 

  • Faris PD, Sainsbury RS (1990) The role of the pontis oralis in the generation of RSA activity in the hippocampus of the guinea pig. Physiol Behav 47:1193–1199

    Article  PubMed  CAS  Google Scholar 

  • Fenik V, Marchenko V, Janssen P, Davies RO, Kubin L (2002) A5 cells are silenced when REM sleep-like signs are elicited by pontine carbachol. J Appl Physiol 93:1448–1456

    PubMed  Google Scholar 

  • Fenik VB, Ogawa H, Davies RO, Kubin L (2005) Carbachol injections into the ventral pontine reticular formation activate locus coeruleus cells in urethane-anesthetized rats. Sleep 28:551–559

    PubMed  Google Scholar 

  • Fonoff ET, Silva CP, Ballester G, Timo-Iaria C (1999) Electro-oscillographic correlation between dorsal raphe nucleus, neocortex and hippocampus during wakefulness before and after serotoninergic inactivation. Braz J Med Biol Res 32:469–472

    Article  PubMed  CAS  Google Scholar 

  • Gaztelu JM, Buño W (1982) Septo-hippocampal relationships during EEG theta rhythm. Electroencephalogr Clin Neurophysiol 54:375–387

    Article  PubMed  CAS  Google Scholar 

  • Gogolák G, Petsche H, Sterc J, Stumpf C (1967) Septum cell activity in the rabbit under reticular stimulation. Brain Res 5:508–510

    Article  PubMed  Google Scholar 

  • Goto M, Swanson LW, Canteras NS (2001) Connections of the nucleus incertus. J Comp Neurol 438:86–122

    Article  PubMed  CAS  Google Scholar 

  • Green K, Rawlins J (1979) Hippocampal theta in rats under urethane: generators and phase relations. Electroencephalogr Clin Neurophysiol 47(4):420–429

    Article  PubMed  CAS  Google Scholar 

  • Hasselmo ME (2005) What is the function of hippocampal theta rhythm? Linking behavioral data to phasic properties of field potential and unit recording data. Hippocampus 15:936–949

    Article  PubMed  Google Scholar 

  • Huerta PT, Lisman JE (1993) Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature 364:723–725

    Article  PubMed  CAS  Google Scholar 

  • Jackson J, Bland BH (2006) Medial septal modulation of the ascending brainstem hippocampal synchronizing pathways in the anesthetized rat. Hippocampus 16:1–10

    Article  PubMed  Google Scholar 

  • Kinney GG, Vogel GW, Feng P (1998) Brainstem carbachol injections in the urethane anesthetized rat produce hippocampal theta rhythm and cortical desynchronization: a comparison of pedunculopontine tegmental versus nucleus pontis oralis injections. Brain Res 809:307–313

    Article  PubMed  CAS  Google Scholar 

  • Kirk IJ, McNaughton N (1991) Supramammillary cell firing and hippocampal rhythmical slow activity. Neuroreport 2:723–725

    Article  PubMed  CAS  Google Scholar 

  • Kirk IJ, Oddie SD, Konopacki J, Bland BH (1996) Evidence for differential control of posterior hypothalamic, supramammillary, and medial mammillary theta-related cellular discharge by ascending and descending pathways. J Neurosci 16:5547–5554

    PubMed  CAS  Google Scholar 

  • Klemm WR (1972) Effects of electric stimulation of brain stem reticular formation on hippocampal theta rhythm and muscle activity in unanesthetized, cervical- and midbrain-transected rats. Brain Res 41:331–344

    Article  PubMed  CAS  Google Scholar 

  • Kocsis B, Li S (2004) In vivo contribution of h-channels in the septal pacemaker to theta rhythm generation. Eur J Neurosci 20:2149–2158

    Article  PubMed  Google Scholar 

  • Kocsis B, Vertes RP (1992) Dorsal raphe neurons: synchronous discharge with the theta rhythm of the hippocampus in the freely behaving rat. J Neurophysiol 68:1463–1467

    PubMed  CAS  Google Scholar 

  • Kocsis B, Vertes RP (1996) Midbrain raphe cell firing and hippocampal theta rhythm in urethane-anaesthetized rats. Neuroreport 7:2867–2872

    Article  PubMed  CAS  Google Scholar 

  • Kocsis B, Prisco GVD, Vertes RP (2001) Theta synchronization in the limbic system: the role of Gudden’s tegmental nuclei. Eur J Neurosci 13:381–388

    Article  PubMed  CAS  Google Scholar 

  • Kramis R, Vanderwolf CH (1980) Frequency-specific RSA-like hippocampal patterns elicited by septal, hypothalamic, and brain stem electrical stimulation. Brain Res 192:383–398

    Article  PubMed  CAS  Google Scholar 

  • Kramis R, Vanderwolf CH, Bland BH (1975) Two types of hippocampal rhythmical slow activity in both the rabbit and the rat: relations to behavior and effects of atropine, diethyl ether, urethane, and pentobarbital. Exp Neurol 49:58–85

    Article  PubMed  CAS  Google Scholar 

  • Lee MG, Chrobak JJ, Sik A, Wiley RG, Buzsáki G (1994) Hippocampal theta activity following selective lesion of the septal cholinergic system. Neuroscience 62:1033–1047

    Article  PubMed  CAS  Google Scholar 

  • Li S, Topchiy I, Kocsis B (2007) The effect of atropine administered in the medial septum or hippocampus on high- and low-frequency theta rhythms in the hippocampus of urethane anesthetized rats. Synapse 61:412–419

    Article  PubMed  CAS  Google Scholar 

  • Ma S, Bonaventure P, Ferraro T, Shen P, Burazin TCD, Bathgate RAD, Liu C, Tregear GW, Sutton SW, Gundlach AL (2007) Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat. Neuroscience 144:165–190

    Article  PubMed  CAS  Google Scholar 

  • Ma S, Olucha-Bordonau FE, Hossain MA, Lin F, Kuei C, Liu C, Wade JD, Sutton SW, Nunez A, Gundlach AL (2009) Modulation of hippocampal theta oscillations and spatial memory by relaxin-3 neurons of the nucleus incertus. Learn Mem 16:730–742

    Article  PubMed  CAS  Google Scholar 

  • Macadar AW, Chalupa LM, Lindsley DB (1974) Differentiation of brain stem loci which affect hippocampal and neocortical electrical activity. Exp Neurol 43:499–514

    Article  PubMed  CAS  Google Scholar 

  • Mitchell SJ, Ranck JB (1980) Generation of theta rhythm in medial entorhinal cortex of freely moving rats. Brain Res 189:49–66

    Article  PubMed  CAS  Google Scholar 

  • Nuñez A, de Andrés I, García-Austt E (1991) Relationships of nucleus reticularis pontis oralis neuronal discharge with sensory and carbachol evoked hippocampal theta rhythm. Exp Brain Res 87:303–308

    Article  PubMed  Google Scholar 

  • Nuñez A, Cervera-Ferri A, Olucha-Bordonau F, Ruiz-Torner A, Teruel V (2006) Nucleus incertus contribution to hippocampal theta rhythm generation. Eur J Neurosci 23:2731–2738

    Article  PubMed  Google Scholar 

  • O’Keefe J, Recce ML (1993) Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3:317–330

    Article  PubMed  Google Scholar 

  • Oddie SD, Bland BH (1998) Hippocampal formation theta activity and movement selection. Neurosci Biobehav Rev 22:221–231

    Article  PubMed  CAS  Google Scholar 

  • Oddie SD, Bland BH, Colom LV, Vertes RP (1994) The midline posterior hypothalamic region comprises a critical part of the ascending brainstem hippocampal synchronizing pathway. Hippocampus 4:454–473

    Article  PubMed  CAS  Google Scholar 

  • Olucha-Bordonau FE, Teruel V, Barcia-González J, Ruiz-Torner A, Valverde-Navarro AA, Martínez-Soriano F (2003) Cytoarchitecture and efferent projections of the nucleus incertus of the rat. J Comp Neurol 464:62–97

    Article  PubMed  Google Scholar 

  • Pavlides C, Greenstein YJ, Grudman M, Winson J (1988) Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta-rhythm. Brain Res 439:383–387

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain. In: Stereotaxic coordinates, 2nd edn. Academic Press, San Diego

  • Petsche H, Stumpf C, Gogolak G (1962) The significance of the rabbit’s septum as a relay station between the midbrain and the hippocampus. I. The control of hippocampus arousal activity by the septum cells. Electroencephalogr Clin Neurophysiol 14:202–211

    Article  PubMed  CAS  Google Scholar 

  • Reinoso-Suárez F, de Andrés I, Rodrigo-Angulo ML, Garzón M (2001) Brain structures and mechanisms involved in the generation of REM sleep. Sleep Med Rev 5:63–77

    Article  PubMed  Google Scholar 

  • Robinson TE, Vanderwolf CH (1978) Electrical stimulation of the brain stem in freely moving rats: II. Effects on hippocampal and neocortical electrical activity, and relations to behavior. Exp Neurol 61:485–515

    Google Scholar 

  • Sainsbury RS, Heynen A, Montoya CP (1987) Behavioral correlates of hippocampal type 2 theta in the rat. Physiol Behav 39:513–519

    Article  PubMed  CAS  Google Scholar 

  • Simões CA, Valle AC, Timo-Iaria C (1996) Correlation between concomitant theta waves in nucleus reticularis pontis oralis and in hippocampus, thalamus and neocortex during dreaming in rats. Braz J Med Biol Res 29:1645–1650

    PubMed  Google Scholar 

  • Siok CJ, Rogers JA, Kocsis B, Hajós M (2006) Activation of alpha7 acetylcholine receptors augments stimulation-induced hippocampal theta oscillation. Eur J Neurosci 23:570–574

    Article  PubMed  CAS  Google Scholar 

  • Skaggs WE, McNaughton BL (1996) Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience. Science 271:1870–1873

    Article  PubMed  CAS  Google Scholar 

  • Stewart M, Fox SE (1990) Do septal neurons pace the hippocampal theta rhythm? Trends Neurosci 13:163–168

    Article  PubMed  CAS  Google Scholar 

  • Takano Y, Hanada Y (2009) The driving system for hippocampal theta in the brainstem: an examination by single neuron recording in urethane-anesthetized rats. Neurosci Lett 455:65–69

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Iijima N, Miyamoto Y, Fukusumi S (2005) Neurons expressing relaxin 3/INSL 7 in the nucleus incertus respond to stress. Eur J Neurosci 21:1659–1670

    Article  PubMed  Google Scholar 

  • Teruel-Martí V, Cervera-Ferri A, Nuñez A, Valverde-Navarro AA, Olucha-Bordonau FE, Ruiz-Torner A (2008) Anatomical evidence for a ponto-septal pathway via the nucleus incertus in the rat. Brain Res 1218:87–96

    Article  PubMed  Google Scholar 

  • Thinschmidt JS, Kinney GG, Kocsis B (1995) The supramammillary nucleus: is it necessary for the mediation of hippocampal theta rhythm? Neuroscience 67:301–312

    Article  PubMed  CAS  Google Scholar 

  • Vanni-Mercier G, Sakai K, Lin JS, Jouvet M (1989) Mapping of cholinoceptive brainstem structures responsible for the generation of paradoxical sleep in the cat. Arch Ital Biol 127:133–164

    PubMed  CAS  Google Scholar 

  • Vertes RP (1981) An analysis of ascending brain stem systems involved in hippocampal synchronization and desynchronization. J Neurophysiol 46:1140–1159

    PubMed  CAS  Google Scholar 

  • Vertes RP (2005) Hippocampal theta rhythm: a tag for short-term memory. Hippocampus 15:923–935

    Article  PubMed  CAS  Google Scholar 

  • Vertes RP, Kocsis B (1997) Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience 81:893–926

    Article  PubMed  CAS  Google Scholar 

  • Vertes RP, Martin GF (1988) Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat. J Comp Neurol 275:511–541

    Article  PubMed  CAS  Google Scholar 

  • Vertes RP, Colom LV, Fortin WJ, Bland BH (1993) Brainstem sites for the carbachol elicitation of the hippocampal theta rhythm in the rat. Exp Brain Res 96:419–429

    Article  PubMed  CAS  Google Scholar 

  • Vertes RP, Hoover WB, Prisco GVD (2004) Theta rhythm of the hippocampus: subcortical control and functional significance. Behav Cogn Neurosci Rev 3:173–200

    Article  PubMed  Google Scholar 

  • Woodnorth MAA, Kyd RJ, Logan BJ, Long MA, McNaughton N (2003) Multiple hypothalamic sites control the frequency of hippocampal theta rhythm. Hippocampus 13:361–374

    Article  PubMed  Google Scholar 

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Acknowledgments

This research has been supported in part by Fondo de Investigaciones Sanitarias (FIS; ISCIII) Research Program (PI061816) and Universitat de València (UV-AE-10-24219) funds. We wish to thank Mario Sendra, Francisco Montes and Jose Luís Cervera for statistical assistance, and Ana Pérez, Araceli Zorrilla and Helen Warburton for the linguistic correction of the final version. Rocio Muñoz’s skilled technical support is gratefully acknowledged.

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  1. Departament d’Anatomia i Embriologia Humana, Facultat de Medicina, Universitat de València, Avd. Blasco Ibañez, 15, 46010, Valencia, Spain

    Ana Cervera-Ferri, Alida Taberner-Cortes, Joana Martínez-Ricós, Amparo Ruiz-Torner & Vicent Teruel-Martí

  2. Grupo de Procesado Digital de Señales, Departament d’Enginyeria Electrònica Facultat de Física, Universitat de València, Doctor Moliner 50, Burjassot, Valencia, Spain

    Juan Guerrero-Martínez & Manuel Bataller-Mompeán

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  1. Ana Cervera-Ferri
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  2. Juan Guerrero-Martínez
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  4. Alida Taberner-Cortes
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  7. Vicent Teruel-Martí
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Correspondence to Ana Cervera-Ferri.

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Cervera-Ferri, A., Guerrero-Martínez, J., Bataller-Mompeán, M. et al. Theta synchronization between the hippocampus and the nucleus incertus in urethane-anesthetized rats. Exp Brain Res 211, 177–192 (2011). https://doi.org/10.1007/s00221-011-2666-3

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