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Role of Pre-Synaptic NMDA Receptors in the Modulation of Inhibitory Synaptic Transmission in Sensory-Motor and Visual Cortical Pyramidal Neurons in Brain Slices of Young Epileptic Mice
Che Lah, Muhammad Hanif; Reza, Faruque; Begum, Tahamina & Abdullah, Jafri Malin
Abstract
Background: Previous studies from animal models have shown that pre-synaptic
NMDA receptors (preNMDARs) are present in the cortex, but the role of inhibition mediated by
preNMDARs during epileptogenesis remains unclear. In this study, we wanted to observe the
changes in GABAergic inhibition through preNMDARs in sensory-motor and visual cortical
pyramidal neurons after pilocarpine-induced status epilepticus.
Methods: Using a pilocarpine-induced epileptic mouse model, sensory-motor and visual
cortical slices were prepared, and the whole-cell patch clamp technique was used to record
spontaneous inhibitory post-synaptic currents (sIPSCs).
Results: The primary finding was that the mean amplitude of sIPSC from the sensory-motor
cortex increased significantly in epileptic mice when the recording pipette contained MK-801 compared to control mice, whereas the mean sIPSC frequency was not significantly different,
indicating that post-synaptic mechanisms are involved. However, there was no significant pre-synaptic
inhibition through preNMDARs in the acute brain slices from pilocarpine-induced
epileptic mice.
Conclusion: In the acute case of epilepsy, a compensatory mechanism of post-synaptic
inhibition, possibly from ambient GABA, was observed through changes in the amplitude without
significant changes in the frequency of sIPSC compared to control mice. The role of preNMDAR-mediated
inhibition in epileptogenesis during the chronic condition or in the juvenile stage
warrants further investigation.
Keywords
pre-synaptic NMDA receptors; sensory-motor cortex; visual cortex; epileptogenesis; whole-cell patch clamp recording; brain slice electrophysiology
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