Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Short-term Epileptiform Activity Potentiates Excitatory Synapses but does not Affect Intrinsic Membrane Properties of Pyramidal Neurons in the Rat Hippocampus in Vitro

Version 1 : Received: 16 September 2021 / Approved: 17 September 2021 / Online: 17 September 2021 (12:45:31 CEST)

A peer-reviewed article of this Preprint also exists.

Ergina, J.L.; Amakhin, D.V.; Postnikova, T.Y.; Soboleva, E.B.; Zaitsev, A.V. Short-term Epileptiform Activity Potentiates Excitatory Synapses but Does Not Affect Intrinsic Membrane Properties of Pyramidal Neurons in the Rat Hippocampus In Vitro. Biomedicines 2021, 9, 1374. Ergina, J.L.; Amakhin, D.V.; Postnikova, T.Y.; Soboleva, E.B.; Zaitsev, A.V. Short-term Epileptiform Activity Potentiates Excitatory Synapses but Does Not Affect Intrinsic Membrane Properties of Pyramidal Neurons in the Rat Hippocampus In Vitro. Biomedicines 2021, 9, 1374.

Abstract

Even brief epileptic seizures can lead to activity-dependent structural remodeling of neural circuitry. Animal models show that the functional plasticity of synapses and changes in the intrinsic excitability of neurons can be crucial for epileptogenesis. However, the exact mechanisms underlying epileptogenesis remain unclear. We induced epileptiform activity in rat hippocampal slices for 15 min using a 4-aminopyridine (4-AP) in vitro model and observed hippocampal hyperexcitability for at least 1 hour. We tested several possible mechanisms of this hyperexcitability, including changes in intrinsic membrane properties of neurons, presynaptic and postsynaptic alterations. Neither input resistance nor other essential biophysical properties of hippocampal CA1 pyramidal neurons were affected by epileptiform activity. The glutamate release probability also remained unchanged, as the frequency of miniature EPSCs and the paired amplitude ratio of evoked responses did not change after epileptiform activity. However, we found an increase in the AMPA/NMDA ratio, suggesting alterations in the properties of postsynaptic glutamatergic receptors. Thus, the increase in excitability of hippocampal neural networks is realized through postsynaptic mechanisms. In contrast, the intrinsic membrane properties of neurons and the probability of glutamate release from presynaptic terminals are not affected in a 4-AP model.

Keywords

temporal lobe epilepsy; hippocampus; 4-aminopyridine; epilepsy model; long-term potentiation; AMPA receptor.

Subject

Biology and Life Sciences, Anatomy and Physiology

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