Increased Dentate Gyrus Excitability in the Intrahippocampal Kainic Acid Mouse Model for Temporal Lobe Epilepsy.
Marijke VergaelenSimona ManzellaKristl VonckErine CraeyJeroen SpanogheMathieu SprengersEvelien CarretteWytse Jan WadmanJean DelbekePaul BoonLars Emil LarsenRobrecht RaedtPublished in: International journal of molecular sciences (2024)
The intrahippocampal kainic acid (IHKA) mouse model is an extensively used in vivo model to investigate the pathophysiology of mesial temporal lobe epilepsy (mTLE) and to develop novel therapies for drug-resistant epilepsy. It is characterized by profound hippocampal sclerosis and spontaneously occurring seizures with a major role for the injected damaged hippocampus, but little is known about the excitability of specific subregions. The purpose of this study was to electrophysiologically characterize the excitability of hippocampal subregions in the chronic phase of the induced epilepsy in the IHKA mouse model. We recorded field postsynaptic potentials (fPSPs) after electrical stimulation in the CA1 region and in the dentate gyrus (DG) of hippocampal slices of IHKA and healthy mice using a multielectrode array (MEA). In the DG, a significantly steeper fPSP slope was found, reflecting higher synaptic strength. Population spikes were more prevalent with a larger spatial distribution in the IHKA group, reflecting a higher degree of granule cell output. Only minor differences were found in the CA1 region. These results point to increased neuronal excitability in the DG but not in the CA1 region of the hippocampus of IHKA mice. This method, in which the excitability of hippocampal slices from IHKA mice is investigated using a MEA, can now be further explored as a potential new model to screen for new interventions that can restore DG function and potentially lead to novel therapies for mTLE.
Keyphrases
- temporal lobe epilepsy
- mouse model
- drug resistant
- transcranial direct current stimulation
- multidrug resistant
- high fat diet induced
- acinetobacter baumannii
- cerebral ischemia
- high throughput
- prefrontal cortex
- spinal cord injury
- single cell
- physical activity
- high glucose
- cognitive impairment
- autism spectrum disorder
- insulin resistance
- wild type
- drug induced
- metabolic syndrome
- risk assessment
- climate change
- human health
- working memory
- mass spectrometry
- intellectual disability
- mesenchymal stem cells
- cystic fibrosis
- subarachnoid hemorrhage