Abstract
Hippocampal theta oscillations are pivotal for hippocampal functions of spatial navigation, learning and memory. In freely behaving animals, hippocampal theta oscillations display bilateral synchronization. Internally generated oscillations in the theta frequency range have also been described in the intact hippocampal preparation in vitro. However, it remains elusive how theta oscillations are synchronized between the left and right hippocampi. We used a preparation of the intact hippocampi interconnected by the ventral hippocampal commissure, prepared from juvenile and adult mice and rats in vitro. Local field potentials and multiunit activity were recorded using extracellular electrodes from the pyramidal cell layer and stratum radiatum of the left and right hippocampi. Neuronal network activity in the left and right hippocampi was found to be organized in theta oscillations, which strongly modulated the firing of CA1 neurons. Both neuronal activity and field potential theta oscillations demonstrated high levels of bilateral synchronization. Theta oscillations persisted on both sides, but their bilateral synchronization was abolished after surgical transection of the ventral hippocampal commissure. Thus, theta oscillations are synchronized in the left and right hippocampi in vitro, and their bilateral synchronization is provided by the ventral commissural connections.
REFERENCES
Suzuki SS, Smith GK (1987) Spontaneous EEG spikes in the normal hippocampus. I. Behavioral correlates, laminar profiles and bilateral synchrony. Electroencephalogr Clin Neurophysiol 67(4): 348–359. https://doi.org/10.1016/0013-4694(87)90123-4
Buzsaki G (1989) Two-stage model of memory trace formation: a role for “noisy” brain states. Neuroscience 31(3): 551–570. https://doi.org/10.1016/0306-4522(89)90423-5
Buzsaki G, Buhl DL, Harris KD, Csicsvari J, Czeh B, Morozov A (2003) Hippocampal network patterns of activity in the mouse. Neuroscience 116(1): 201–211. https://doi.org/10.1016/S0306-4522(02)00669-3
Buzsaki G (2015) Hippocampal sharp wave-ripple: A cognitive biomarker for episodic memory and planning. Hippocampus 25(10): 1073–1188. https://doi.org/10.1002/hipo.22488
Carr MF, Karlsson MP, Frank LM (2012) Transient slow gamma synchrony underlies hippocampal memory replay. Neuron 75(4): 700–713. https://doi.org/10.1016/j.neuron.2012.06.014
Shinohara Y, Hosoya A, Hirase H (2013) Experience enhances gamma oscillations and interhemispheric asymmetry in the hippocampus. Nat Commun 4: 1652. https://doi.org/10.1038/ncomms2658
Pfeiffer BE, Foster DJ (2015) PLACE CELLS. Autoassociative dynamics in the generation of sequences of hippocampal place cells. Science 349(6244): 180–183. https://doi.org/10.1126/science.aaa9633
Wang Y, Toprani S, Tang Y, Vrabec T, Durand DM (2014) Mechanism of highly synchronized bilateral hippocampal activity. Exp Neurol 251: 101–111. https://doi.org/10.1016/j.expneurol.2013.11.014
Benito N, Martin-Vazquez G, Makarova J, Makarov VA, Herreras O (2016) The right hippocampus leads the bilateral integration of gamma-parsed lateralized information. Elife 5: e16658. https://doi.org/10.7554/eLife.16658
Tanaka M, Wang X, Mikoshiba K, Hirase H, Shinohara Y (2017) Rearing-environment-dependent hippocampal local field potential differences in wild-type and inositol trisphosphate receptor type 2 knockout mice. J Physiol 595(20): 6557–6568. https://doi.org/10.1113/JP274573
Valeeva G, Nasretdinov A, Rychkova V, Khazipov R (2019) Bilateral Synchronization of Hippocampal Early Sharp Waves in Neonatal Rats. Front Cell Neurosci 13: 29. https://doi.org/10.3389/fncel.2019.00029
Khazipov R, Holmes GL (2003) Synchronization of kainate-induced epileptic activity via GABAergic inhibition in the superfused rat hippocampus in vivo. J Neurosci 23(12): 5337–5341. https://doi.org/10.1523/JNEUROSCI.23-12-05337.2003
Buzsaki G (2002) Theta Oscillations in the hippocampus. Neuron 33: 325–340. https://doi.org/10.1016/s0896-6273(02)00586-x
Buzsaki G, Moser EI (2013) Memory, navigation and theta rhythm in the hippocampal-entorhinal system. Nat Neurosci 16(2): 130–138. https://doi.org/10.1038/nn.3304
Colgin LL (2013) Mechanisms and functions of theta rhythms. Annu Rev Neurosci 36: 295–312. https://doi.org/10.1146/annurev-neuro-062012-170330
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(7): 936–949. https://doi.org/10.1002/hipo.20116.
Mizuseki K, Sirota A, Pastalkova E, Buzsaki G (2009) Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop. Neuron 64(2): 267–80. https://doi.org/10.1016/j.neuron.2009.08.037
Shinohara Y, Hosoya A, Yahagi K, Ferecsko AS, Yaguchi K, Sik A, Itakura M, Takahashi M, Hirase H (2012) Hippocampal CA3 and CA2 have distinct bilateral innervation patterns to CA1 in rodents. Eur J Neurosci 35(5): 702–710. https://doi.org/10.1111/j.1460-9568.2012.07993.x
Fernandez-Ruiz A, Oliva A, Nagy GA, Maurer AP, Berenyi A, Buzsaki G (2017) Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling. Neuron 93: 1213–1226. https://doi.org/10.1016/j.neuron.2017.02.017
Buzsaki G, Eidelberg E (1982) Convergence of associational and commissural pathways on CA1 pyramidal cells of the rat hippocampus. Brain Res 237(2): 283–295. https://doi.org/10.1016/0006-8993(82)90442-5
Goutagny R, Jackson J, Williams S (2009) Self-generated theta oscillations in the hippocampus. Nature Neuroscience 12(12): 1491–1493. https://doi.org/10.1038/nn.2440
Ducharme G, Lowe GC, Goutagny R, Williams S (2012) Early Alterations in Hippocampal Circuitry and Theta Rhythm Generation in a Mouse Model of Prenatal Infection: Implications for Schizophrenia. Plos One 7(1): 8. https://doi.org/10.1371/journal.pone.0029754
Jackson J, Amilhon B, Goutagny R, Bott JB, Manseau F, Kortleven C, Bressler SL, Williams S (2014) Reversal of theta rhythm flow through intact hippocampal circuits. Nature Neuroscience 17(10): 1362–1370. https://doi.org/10.1038/nn.3803
Amilhon B, Huh CYL, Manseau F, Ducharme G, Nichol H, Adamantidis A, Williams S (2015) Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency. Neuron 86(5): 1277–1289. https://doi.org/10.1016/j.neuron.2015.05.027
Khalilov I, Dzhala V, Medina I, Leinekugel X, Melyan Z, Lamsa K, Khazipov R, Ben-Ari Y (1999) Maturation of kainate-induced epileptiform activities in interconnected intact neonatal limbic structures in vitro. Eur J Neurosci 11(10): 3468–3480. https://doi.org/10.1046/j.1460-9568.1999.00768.x
Khalilov I, Esclapez M, Medina I, Aggoun D, Lamsa K, Leinekugle X, Khazipov R, Ben-Ari Y (1997) A novel in vitro preparation: the intact hippocampal formation. Neuron 19(4): 743–749. https://doi.org/10.1016/s0896-6273(00)80956-3
Khazipov R, Desfreres L, Khalilov I, Ben-Ari Y (1999) Three-independent-compartment chamber to study in vitro commissural synapses. J Neurophysiol 81(2): 921–924. https://doi.org/10.1152/jn.1999.81.2.921
Leinekugel X, Khalilov I, Ben-Ari Y, Khazipov R (1998) Giant depolarizing potentials: the septal pole of the hippocampus paces the activity of the developing intact septohippocampal complex in vitro. J Neurosci 18(16): 6349–6357. https://doi.org/10.1523/JNEUROSCI.18-16-06349.1998
Khalilov I, Holmes GL, Ben Ari Y (2003) In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures. Nat Neurosci 6(10): 1079–1085. https://doi.org/10.1038/nn1125
Khalilov I, Le Van QM, Gozlan H, Ben Ari Y (2005) Epileptogenic Actions of GABA and Fast Oscillations in the Developing Hippocampus. Neuron 48(5): 787–796. https://doi.org/10.1016/j.neuron.2005.09.026
Nardou R, Ben-Ari Y, Khalilov I (2009) Bumetanide, an NKCC1 antagonist, does not prevent formation of epileptogenic focus but blocks epileptic focus seizures in immature rat hippocampus. J Neurophysiol 101(6): 2878–2888. https://doi.org/10.1152/jn.90761.2008
Ylinen A, Soltesz I, Bragin A, Penttonen M, Sik A, Buzsaki G (1995) Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells. Hippocampus 5(1): 78–90. https://doi.org/10.1002/hipo.450050110
Buzsaki G, Czopf J, Kondakor I, Kellenyi L (1986) Laminar distribution of hippocampal rhythmic slow activity (RSA) in the behaving rat: current-source density analysis, effects of urethane and atropine. Brain Res 365(1): 125–137. https://doi.org/10.1016/0006-8993(86)90729-8
Kamondi A, Acsady L, Wang XJ, Buzsaki G (1998) Theta oscillations in somata and dendrites of hippocampal pyramidal cells in vivo: activity-dependent phase-precession of action potentials. Hippocampus 8(3): 244–261. https://doi.org/10.1002/(SICI)1098-1063(1998)8:3<244::AID-HIPO7>3.0.CO;2-J
Funding
This work was supported by the National Research Agency (Project No. ANR-21-CE16-0005-01 “DevHippo”), and as part of the Priority 2030 research program at Kazan Federal University.
Author information
Authors and Affiliations
Contributions
Conceptualization and experimental design (R.Kh.), data collection (I.Kh.), data processing (A.G.), writing and editing the manuscript (R.Kh., A.G., I.Kh.).
Corresponding author
Ethics declarations
COMPLIANCE WITH ETHICAL STANDARDS
All procedures performed with the involvement of animals complied with ethical standards approved by legal acts of the Russian Federation, the principles of the Basel Declaration, and recommendations of the Directive 2010/63/EU for animal experiments. All animal use protocols were approved by the French National Institute of Health and Medical Research (APAFIS #16992- 2020070612319346 v2) and Local Ethics Committee of Kazan Federal University (#24/ 22.09.2020).
CONFLICT OF INTEREST
The authors declare that they have neither evident nor potential conflict of interest related to the publication of this article.
Additional information
Translated by A. Polyanovsky
Russian Text © The Author(s), 2023, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2023, Vol. 59, No. 3, pp. 207–214https://doi.org/10.31857/S004445292303004X.
Rights and permissions
About this article
Cite this article
Khalilov, I., Gainutdinov, A. & Khazipov, R. Bilateral Synchronization of Hippocampal Theta Oscillations in vitro. J Evol Biochem Phys 59, 719–726 (2023). https://doi.org/10.1134/S0022093023030067
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0022093023030067