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Updated: Jul 16, 2026
Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays
Published on: May 15, 2018
Synaptic responses in superficial layers of medial entorhinal cortex from rats with kainate-induced epilepsy
Else A Tolner1, Christiane Frahm, Robert Metzger
1Johannes-Müller-Institute of Physiology at the Charité, Humboldt University Berlin, Tucholskystr. 2, 10117 Berlin, Germany. else.tolner@helsinki.fi
Abstract:
Mesial temporal lobe epilepsy patients often display shrinkage of the entorhinal cortex, which has been attributed to neuronal loss in medial entorhinal cortex layer III (MEC-III). MEC-III neuronal loss is reproduced in chronic epileptic rats after kainate-induced (KA) status epilepticus. Here we examined, in vitro, functional changes in superficial entorhinal cortex layers. Alterations in superficial layer circuitry were suggested by showing that presubiculum, parasubiculum and deep MEC stimulation evoked 100-300 Hz field potential transients and prolonged EPSPs (superimposed on IPSPs) in superficial MEC which were partially blocked by APV (in contrast to control) and fully blocked by CNQX. Contrary to controls, bicuculline (5 and 30 microM) had minor effects on evoked field potentials in KA rats. GAD65/67 in situ hybridization revealed preserved interneurons in MEC-III. In conclusion, hyperexcitability in superficial MEC neurons is not due to loss of GABAergic interneurons and probably results from alterations in synaptic connectivity within superficial MEC.
Insights
Mesial temporal lobe epilepsy involves entorhinal cortex changes. In epileptic rats, superficial entorhinal cortex hyperexcitability arises from altered synaptic connections, not GABAergic interneuron loss.
Area of Science:
- Neuroscience
- Epilepsy Research
- Computational Neuroscience
Background:
- Mesial temporal lobe epilepsy (MTLE) is associated with entorhinal cortex (EC) atrophy.
- Neuronal loss in medial entorhinal cortex layer III (MEC-III) is a key pathological feature in MTLE.
- Kainate-induced (KA) status epilepticus in rats models MEC-III neuronal loss seen in chronic epilepsy.
Purpose of the Study:
- To investigate functional changes in superficial entorhinal cortex layers in a rat model of chronic epilepsy.
- To determine the mechanisms underlying hyperexcitability in the superficial EC following KA-induced status epilepticus.
- To assess the role of GABAergic interneurons in observed functional alterations.
Main Methods:
- In vitro electrophysiological recordings from superficial entorhinal cortex slices.
- Stimulation of afferent pathways (presubiculum, parasubiculum, deep MEC) to evoke field potentials.
- Pharmacological manipulations using APV, CNQX, and bicuculline to probe synaptic mechanisms.
- In situ hybridization for GAD65/67 to assess GABAergic interneuron integrity.
Main Results:
- KA rats exhibited altered evoked field potentials in superficial MEC, including prolonged excitatory postsynaptic potentials (EPSPs).
- These alterations were partially blocked by APV (NMDA receptor antagonist) and fully blocked by CNQX (AMPA receptor antagonist).
- Bicuculline (GABA antagonist) had minimal effects on evoked potentials in KA rats, unlike in controls.
- GAD65/67 expression indicated preserved interneuron populations in MEC-III.
Conclusions:
- Superficial MEC neurons in KA rats display hyperexcitability.
- This hyperexcitability is not caused by a loss of GABAergic interneurons.
- The findings suggest that altered synaptic connectivity within the superficial MEC contributes to hyperexcitability in epilepsy.
