The hippocampus and medial entorhinal cortex (MEC) interact by means of bidirectional connections and play an important role in the processing, memorization, and reproduction of information. Data obtained in healthy animals show that the θ and γ oscillations are critical activities necessary for the interaction of the hippocampus and the MEC in signal processing. At the same time, these structures are among the most vulnerable parts of the brain to hyperactivation leading to excitotoxic damage and neuron death. In the present study toxicity was provoked by systemic administration of kainic acid (KA), inducing the development of status epilepticus. In control rats given physiological saline and rats given injections of KA, local field potentials were recorded simultaneously in hippocampal field CA1 and the MEC during exploratory behavior in an open field. A clearly apparent θ rhythm (4–10 Hz) was observed, along with a slow γ rhythm (25–50 Hz) and a fast γ rhythm (55–100 Hz) in the hippocampus and MEC of animals of both groups. Movement of control animals to the center of the open field was accompanied by an increase in the frequency of the θ rhythm and a decrease in the frequency of the fast γ rhythm in the hippocampus; the MEC showed a decrease in the power of the slow γ rhythm. This was not seen in rats given KA. This group also showed impairment to the phase-amplitude modulation of MEC activity by the hippocampal θ rhythm: changes in this modulation on movement of animals from the peripheral zones to the center of the open field were significantly less marked than in controls. There was also a significant increase in θ coherence between the hippocampus and MEC for all locations of the animal in the open field. Changes in the characteristics of rhythms in hippocampus-entorhinal interactions are potential biomarkers for impairments to the coding of spatial information and its retrieval from memory due to status epilepticus and often leading to the development of a convulsive focus in the temporal structures of the brain.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Axmacher, N., Henseler, M. M., Jensen, O., et al., “Cross-frequency coupling supports multi-item working memory in the human hippocampus,” Proc. Natl. Acad. Sci. USA, 107, 3228–3233 (2010).
Bastos, A. M., Vezol, J., and Fries, P., “Communication through coherence with inter-areal delays,” Curr. Opin. Neurobiol., 31, 173–180 (2015).
Belluscio, M. A., Mizuseki, K., Schmidt, R., et al., “Cross-frequency phase–phase coupling between theta and gamma oscillations in the hippocampus,” J. Neurosci., 32, 423–435 (2012).
Benchenane, K., Peyrache, A., Khamassi, M., et al., “Coherent theta oscillations and reorganization of spike timing in the hippocampal-prefrontal network upon learning,” Neuron, 66, No. 6, 921–936 (2010).
Betjemann, J. P. and Lowenstein, D. H., “Status epilepticus in adults,” Lancet Neurol., 14, No. 6, 615–624 (2015).
Bland, B. H., “The physiology and pharmacology of hippocampal formation theta rhythms,” Prog. Neurobiol., 26, 1–54 (1986).
Bouyer, J., Montaron, M., and Rougeul, A., “Fast fronto-parietal rhythms during combined focused attentive behaviour and immobility in cat: cortical and thalamic localizations,” Electroencephalogr. Clin. Neurophysiol., 51, 244–252 (1981).
Bragin, A., Engel, J., Jr., Wilson, C. L., et al., “Electrophysiologic analysis of a chronic seizure model after unilateral hippocampal KA injection,” Epilepsia, 40, 1210–1221 (1999).
Bragin, A., Jandó, G., Nádasdy, Z., et al., “Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat,” J. Neurosci., 15, 47–60 (1995).
Brun, V. H., Otnass, M. K., Molden, S., et al., “Place cells and place recognition maintained by direct entorhinal-hippocampal circuitry,” Science, 296, 2243–2246 (2002).
Buzsáki, G. and Moser, E. I., “Memory, navigation and theta rhythm in the hippocampal-entorhinal system,” Nat. Neurosci., 16, 130–138 (2013).
Buzsáki, G. and Wang, X. J., “Mechanisms of gamma oscillations,” Annu. Rev. Neurosci., 35, 203–225 (2010).
Buzsáki, G., “Theta oscillations in the hippocampus,” Neuron, 33, 325–340 (2002).
Buzsáki, G., Rhythms of the Brain, Oxford University Press, New York (2006).
Canolty, R. T. and Knight, R. T., “The functional role of cross-frequency coupling,” Trends Cogn. Sci., 14, 506–515 (2010).
Canolty, R. T., Edwards, E., Dalal, S. S., et al., “Oscillatory phase coupling coordinates anatomically dispersed functional cell assemblies,” Proc. Natl. Acad. Sci. USA, 107, No. 40, 17356–17361 (2010).
Canolty, R., Edwards, E., Dalal, S., et al., “High gamma power is phaselocked to theta oscillations in human neocortex,” Science, 313, 1626–1628 (2006).
Cavanagh, J. F., Cohen, M. X., and Allen, J. J., “Prelude to and resolution of an error: EEG phase synchrony reveals cognitive control dynamics during action monitoring,” J. Neurosci., 29, 98–105 (2009).
Chauvière, L., Rafrafi, N., Thinus-Blanc, C., et al., “Early deficits in spatial memory and theta rhythm in experimental temporal lobe epilepsy,” J. Neurosci., 29, No. 17, 5402–5410 (2009).
Colgin, L. L. and Moser, E. I., “Gamma oscillations in the hippocampus,” Physiology (Bethesda), 25, 319–329 (2010).
Colgin, L. L., “Do slow and fast gamma rhythms correspond to distinct functional states in the hippocampal network?” Brain Res., 1621, 309–315. (2015a).
Colgin, L. L., “Mechanisms and functions of theta rhythms,” Annu. Rev. Neurosci., 36, 295–312 (2013).
Colgin, L. L., “Rhythms of the hippocampal network,” Nat. Rev. Neurosci., 17, No. 4, 239–249 (2016).
Colgin, L. L., “Theta-gamma coupling in the entorhinal-hippocampal system,” Curr. Opin. Neurobiol., 31, 45–50 (2015b).
Colgin, L. L., Denninger, T., Fyhn, M., et al., “Frequency of gamma oscillations routes flow of information in the hippocampus,” Nature, 462, No. 7271, 353–357 (2009).
Dupont, S., Van de Moortele, P., Samson, S., et al., “Episodic memory in left temporal lobe epilepsy: a functional MRI study,” Brain, 123, 1722 (2000).
Fell, J. and Axmacher, N., “The role of phase synchronization in memory processes,” Nat. Rev. Neurosci., 12, 105–118 (2011).
Fell, J., Klave, P., Lehnert, K., et al., “Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling,” Nat. Neurosci., 4, 1259–1264 (2001).
Fell, J., Ludowig, E., Rosburg, T., et al., “Phase-locking within human mediotemporal lobe predicts memory formation,” Neuroimage, 43, 410–419 (2008).
Freund, T. F. and Buzsaki, G., “Interneurons of the hippocampus,” Hippocampus, 6, 347–470 (1996).
Fries, P., “Neuronal gamma-band synchronization as a fundamental process in cortical computation,” Annu. Rev. Neurosci., 32, 209–224 (2009).0
Froriep, U. P., Kumar, A., Cosandier-Rimélé, D., et al., “Altered theta coupling between medial entorhinal cortex and dentate gyrus in temporal lobe epilepsy,” Epilepsia, 53, 1937–1947 (2012).
Green, J. D. and Arduini, A. A., “Hippocampal electrical activity in arousal,” J. Neurophysiol, 17, No. 6, 533–557 (1954).
Gregoriou, G. G., Gotts, S. J., Zhou, H., and Desimone, R., “Highfrequency, long-range coupling between prefrontal and visual cortex during attention,” Science, 324, 1207–1210 (2009).
Hafting, T., Fyhn, M., Bonnevie, T., et al., “Hippocampus-independent phase precession in entorhinal grid cells,” Nature, 453, 1248–1252 (2008).
Hafting, T., Fyhn, M., Molden, S., et al., “Microstructure of a spatial map in the entorhinal cortex,” Nature, 436, 801–806 (2005).
Hasselmo, M. E. and Stern, C. E., “Theta rhythm and the encoding and retrieval of space and time,” Neuroimage, 85, No. Part 2, 656–666 (2014).
Hellier, J. L., Patrylo, P. R., Buckmaster, P. S., et al., “Recurrent spontaneous motor seizures after repeated low-dose systemic treatment with kainate: assessment of a rat model of temporal lobe epilepsy,” Epilepsy Res., 31, 73–84 (1998).
Helmstaedter, C., “Effects of chronic epilepsy on declarative memory systems,” Prog. Brain Res., 135, 439–453 (2002).
Hurtado, J. M., Rubchinsky, L. L., and Sigvardt, K. A., “Statistical method for detection of phase-locking episodes in neural oscillations,” J. Neurophysiol, 91, 1883–1898 (2004).
Inostroza, M., Brotons-Mas, J. R., Laurent, F., et al., “Specific impairment of ‘what-where-when’ episodic-like memory in experimental models of temporal lobe epilepsy,” J. Neurosci., 33, 17749–17762 (2013).
Jensen, O. and Lisman, J. E., “Hippocampal sequence-encoding driven by a cortical multi-item working memory buffer,” Trends Neurosci., 28, 67–72 (2005).
Kemere, C., Carr, M. F., Karlsson, M. P., and Frank, L. M., “Rapid and continuous modulation of hippocampal network state during exploration of new places,” PLoS One, 8, e73114 (2013).
Kloosterman, F., Van Haeften, T., Witter, M. P., and Lopes Da Silva, F. H., “Electrophysiological characterization of interlaminar entorhinal connections: an essential link for re-entrance in the hippocampal-entorhinal system,” Eur. J. Neurosci., 18, 3037–3052 (2003).
Kuniishi, H., Ichisaka, S., Yamamoto, M., et al., “Early deprivation increases high-leaning behavior, a novel anxiety-like behavior, in the open field test in rats,” Neurosci. Res., 123, 27–35 (2017).
Lega, B., Burke, J., Jacobs, J., and Kahana, M. J., “Slow-theta-to-gamma phase amplitude coupling in human hippocampus supports the formation of new episodic memories,” Cereb. Cortex, 26, 268–278 (2016).
Lemesle, B., Planton, M., Pagès, B., and Pariente, J., “Accelerated long-term forgetting and autobiographical memory disorders in temporal lobe epilepsy: One entity or two?” Rev. Neurol. (Paris), 173, No. 7–8, 498–505 (2017).
Lin, D. Q., Cai, X. Y., Wang, C. H., et al., “Optimal concentration of necrostatin-1 for protecting against hippocampal neuronal damage in mice with status epilepticus,” Neural Regen. Res., 15, No. 5, 936–943 (2020).
Livanov, M. N., Krylov V. Yu., Ostrjakova, T. V., and Shulgina, G. I., “Slow field potential oscillations as one of the basic mechanisms of integrative activity of neurons [proceedings],” Act. Nerv. Super. (Praha), 19, 43–44 (1977).
Lothman, E. W., Bertram, E. H., Kapur, J., and Stringer, J. L., “Recurrent spontaneous hippocampal seizures in the rats as a chronic sequela to limbic status epilepticus,” Epilepsy Res., 6, 110–118 (1990).
Malkov, A. E., Shubina, L. V., and Kitchigina, V. F., “Effects of endocannabinoid-related compounds on the activity of septal and hippocampal neurons in a model of kainic neurotoxicity: study ex vivo,” Opera Med. Physiol., 4, No. 1, 23–34 (2018).
Mazarati, A., Bragin, A., Baldwin, R., et al., “Epileptogenesis after selfsustaining status epilepticus,” Epilepsia, 43, Suppl. 5, 74–80 (2002).
Montgomery, S. M., Sirota, A., and Buzsáki, G., “Theta and gamma coordination of hippocampal networks during waking and rapid eye movement sleep,” J. Neurosci., 28, 6731–6741 (2008).
Moser, E. I., Roudi, Y., Witter, M., et al., “Grid cells and cortical representation,” Nat. Rev. Neurosci., 15, 466–481 (2014).
Nácher, V., Ledberg, A., Deco, G., and Romo, R., “Coherent delta-band oscillations between cortical areas correlate with decision making,” Proc. Natl. Acad. Sci. USA, 110, 15,085–15,090 (2013).
Newman, E. L., Gillet, S. N., Climer, J. R., and Hasselmo, M. E., “Cholinergic blockade reduces theta-gamma phase amplitude coupling and speed modulation of theta frequency consistent with behavioral effects on encoding,” J. Neurosci., 33, 19635–19646 (2013).
O’Keefe, J. and Conway, D. H., “Hippocampal place units in the freely moving rat: why they fire where they fire,” Exp. Brain Res., 31, No. 4, 573–590. (1978).
O’Keefe, J. and Recce, M. L., “Phase relationship between hippocampal place units and the EEG theta rhythm,” Hippocampus, 3, No. 3, 317–330 (1993).
O’Keefe, J., “Place units in the hippocampus of the freely moving rat,” Exp. Neurol., 51, 78–109 (1976).
Paxinos, G. and Watson, C., The Rat Brain in Stereotaxic Coordinates, Academic Press, Sydney (1998).
Petsche, H. and Stumpf, C., “The origin of theta-rhythm in the rabbit hippocampus,” Wien. Klin. Wochenschr., 74, 696–700 (1962).
Prut, L. and Belzung, C., “The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review,” Eur. J. Pharmacol., 463, No. 1–3, 3–33 (2003).
Rodriguez, E., George, N., Lachaux, J. P., et al., “Perception’s shadow: long-distance synchronization of human brain activity,” Nature, 397, 430–433 (1999).
Schomburg, E. W., Fernández-Ruiz, A., Mizuseki, K., et al., “Theta phase segregation of input-specific gamma patterns in entorhinal-hippocampal networks,” Neuron, 84, 470–485 (2014).
Siegel, M., Warden, M. R., and Mille, E. K., “Phase-dependent neuronal coding of objects in short-term memory,” Proc. Natl. Acad. Sci. USA, 106, 21341–21346 (2009).
Steffenach, H. A., Sloviter, R. S., Mose, E. I., and Moser, M. B., “Impaired retention of spatial memory after transection of longitudinally oriented axons of hippocampal CA3 pyramidal cells,” Proc. Natl. Acad. Sci. USA, 99, 3194–3198 (2002).
Steward, O., “Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat,” J. Comp. Neurol., 167, 285–314 (1976).
Strogatz, S. H., Nonlinear Dynamics and Chaos: With Applications to Physics, Biology, Chemistry and Engineering, Perseus Books, Cambridge, MA (2003).
Stumpf, C., Petsche, H., and Gogolak, G., “The significance of the rabbit’s septum as a relay station between the midbrain and the hippocampus. II. The differential influence of drugs upon both the septal cell firing pattern and the hippocampus theta activity,” Electroencephalogr. Clin. Neurophysiol., 14, 212–219 (1962).
Sutherland, R. J., Whishaw, I. Q., and Kolb, B., “A behavioural analysis of spatial localization following electrolytic, kainate- or colchicine-induced damage to the hippocampal formation in the rat,” Behav. Brain Res., 7, No. 2, 133–153 (1983).
Tan, H. M., Wills, T. J., and Cacucci, F., “The development of spatial and memory circuits in the rat,” Wiley Interdisc. Rev. Cogn. Sci., 8, No. 3, (2017).
Taube, J. S., Muller, R. U., and Ranck, J. B., “Head-direction cells recorded from the postsubiculum in freely moving rats. II. Effects of environmental manipulations,” J. Neurosci., 10, 36–447 (1990).
Tort, A. B. L., Komorowski, R. W., Manns, J. R., et al., “Theta-gamma coupling increases during the learning of item-context associations,” Proc. Natl. Acad. Sci. USA, 106, 20,942–20,947 (2009).
Tramoni-Negre, E., Lambert, I., Bartolomei, F., and Felician, O., “Longterm memory deficits in temporal lobe epilepsy,” Rev. Neurol. (Paris), 73, No. 7–8, 490–497 (2017).
Treves, A. and Rolls, E. T., “Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network,” Hippocampus, 2, 189–199 (1992).
Vanderwolf, C., “Hippocampal electrical activity and voluntary movement in the rat,” Electroencephalogr. Clin. Neurophysiol., 26, 407–418 (1969).
Vinogradova, O. S., “Expression, control, and probable functional significance of the neuronal theta-rhythm,” Prog. Neurobiol., 45, 523–583 (1995).
Vinogradova, O. S., “Hippocampus as comparator: role of the two input and two output systems of the hippocampus in selection and registration of information,” Hippocampus, 11, 578–598 (2001).
Vinogradova, O. S., Kitchigina, V. F., Kudina, T. A., and Kutyreva, E. V., “Oscillatory θ processes in neurons in the septohippocampal system and their modulation by stem structures,” Usp. Sovr. Biol., 120, 103–112 (2000).
Womelsdorf, T., Fries, P., Mitra, P. P., and Desimone, R., “Gamma-band synchronization in visual cortex predicts speed of change detection,” Nature, 439, 733–736 (2006).
Wulff, P., Ponomarenko, A. A., Bartos, M., et al., “Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons,” Proc. Natl. Acad. Sci. USA, 106, 3561–3566 (2009).
Zheng, C., Bieri, K. W., Hwaun, E., and Colgin, L. L., “Fast gamma rhythms in the hippocampus promote encoding of novel object-place pairings,” eNeuro, 3, No. 2, pii: ENEURO.0001-16.2016 (2016).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 70, No. 3, pp. 394–410, May–June, 2020.
Rights and permissions
About this article
Cite this article
Malkov, A.E., Shevkova, L.V., Latyshkova, A.A. et al. Rhythmic Activity in the Hippocampus and Entorhinal Cortex is Impaired in a Model of Kainate Neurotoxicity in Rats in Free Behavior. Neurosci Behav Physi 51, 73–84 (2021). https://doi.org/10.1007/s11055-020-01041-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-020-01041-7