The Impact of Febrile Seizures on Synaptic Transmission in the Hippocampus of Rats with Freezing-Induced Focal Cortical Dysplasia

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Abstract

Febrile seizures (FS) in early childhood can lead to the development of epilepsy; however, in most cases, they resolve without consequences. The neurophysiological mechanisms that protect the brain from the effects of FS remain poorly understood. It is also known that the risk of epilepsy significantly increases if a child has congenital abnormalities in the structure of the cerebral cortex. In this study, we examined functional changes in the hippocampus of young rats subjected to FS on the 10th postnatal day (P10) with freezing-induced focal cortical dysplasia (FCD) on P0. Experiments were conducted on three groups of animals: 1) control group (Ctrl) – rats without FS and FCD; 2) FS group – rats subjected to hyperthermia-induced FS on P10; 3) FS+FCD group – rats with cortical freezing on P0 and FS on P10. Using recordings of local synaptic potentials in the CA1 region of the hippocampus, we found that FS led to significant changes in synaptic transmission. In the FS group, there was an increase in the threshold for population spike generation, a decrease in the synaptic transmission efficacy ratio, and an increase in the paired-pulse ratio. These changes indicate reduced activity of CA3-CA1 glutamatergic synapses, which may represent a compensatory response preventing epileptogenesis. However, in the FS+FCD group, such compensatory changes were absent: synaptic transmission parameters did not differ from those in the control group. This suggests that FCD impedes the activation of protective mechanisms in the hippocampus in response to FS. Thus, the presence of cortical dysplasia may increase the risk of epilepsy following FS by 20 blocking natural compensatory processes. Our results highlight the importance of studying the interaction between congenital cortical developmental abnormalities and the consequences of FS for understanding the mechanisms of epileptogenesis.

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About the authors

T. Y. Postnikova

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Author for correspondence.
Email: tapost2@mail.ru
Russian Federation, St. Petersburg

A. V. Zaitsev

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: tapost2@mail.ru
Russian Federation, St. Petersburg

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2. Fig. 1. Freeze-induced cortical malformation. (a) - Representative example of a rat brain (P21) that sustained a freezing-induced lesion at age P0, resulting in a longitudinal microvillus in the left sensorimotor cortex, indicated by arrows. (b) - Representative example of a Nissl stained coronal slice through a dysplastic lesion in the rat cerebral cortex. The image clearly shows the formed four-layered microvillus. The location of the freezing focus is indicated by the arrow. (c) - Schematic representation of the freeze-induced microvillus.

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3. Fig. 2. Thresholds for the occurrence of postsynaptic population spikes in the rat hippocampus. (a) - Schematic representation of electrode locations in a hippocampal slice. (b) - Representative examples of field responses in three groups. The recording where postsynaptic population spike is first seen is highlighted in red. (c) - Diagram showing the magnitude of the threshold for the occurrence of postsynaptic population spikes. * - p < 0.05; ** - p < 0.01 (Mann-Whitney posterior test).

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4. Fig. 3. Input-output (I/O) relationships for pVPSP amplitudes (a) and presynaptic prPS amplitudes (b) recorded from the hippocampus in the CA1 region in control (Ctrl) and FS rats. (c) - Representative examples of I/O relationships between pVPSP and prPS amplitudes in hippocampal slices from control and FS rats. (d) - Maximum I/O slopes were smaller in rats with FS than in control animals. * - p < 0.05 (Tukey's posterior test).

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5. Fig. 4. The magnitude of short-term synaptic facilitation is increased in FS-treated rats. (a) - Representative examples of evoked field responses in the CA1 field of the hippocampus of control (Ctrl) and experimental (FS and FS+FCD) groups at an interstimulus interval of 50 ms. (b) - Magnitude of short-term synaptic facilitation at 50 ms interstimulus interval in control and experimental groups. * p < 0.05, *** p < 0.001 (Tukey's posterior test).

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