Rhythmic Activity in the Hippocampus and Entorhinal Cortex is Impaired in a Model of Kainate Neurotoxicity in Rats in Fr

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Rhythmic Activity in the Hippocampus and Entorhinal Cortex Is Impaired in a Model of Kainate Neurotoxicity in Rats in Free Behavior A. E. Malkov, L. V. Shevkova, A. A. Latyshkova, and V. F. Kitchigina

UDC 612.821.6+612.822.3

Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 70, No. 3, pp. 394–410, May–June, 2020. Original article received September 9, 2019. Revised version received December 3, 2019. Accepted December 16, 2019. 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. Keywords: open field, free behavior, exploratory activity, hippocampus, medial entorhinal cortex, oscillation, θ rhythm, γ rhythm, phase-amplitude modulation, intrafrequency coherence, kainate neurotoxicity.

The hippocampus and entorhinal cortex, which form the navigation system of the brain [Buzsáki and Moser, 2013], interact with each other via bidirectional connections [Steward, 1976; Kloosterman et al., 2003]. The medial part of the entorhinal cortex (MEC), like the hippocampus, contains neurons whose activity depends on the animal’s loca