NMDAR-independent hippocampal long-term depression impairment after status epilepticus in a lithium-pilocarpine model of temporal lobe epilepsy.

Temporal lobe epilepsy is usually associated with cognitive decline and memory deficits. Despite numerous existing studies on various animal models, the mechanisms of these deficits remain largely unclear. A specific form of long-term synaptic efficacy changes-long-term depression (LTD)-is thought to play an important role in memory formation and learning. However, extremely little is known about the possible alteration of LTD induction and dynamics after a status epilepticus (SE). In this work, we investigated the acute and delayed effects of lithium-pilocarpine-induced SE on NMDAR-dependent and NMDAR-independent hippocampal LTD in vitro. We found that SE affected the NMDAR-dependent and NMDAR-independent forms of LTD in different manners. The NMDAR-dependent form of LTD was almost intact 3 days after SE, but it switched from a predominantly presynaptic to a more postsynaptic locus of expression. In contrast, the NMDAR-independent LTD in the hippocampal Schaffer collaterals-CA1 synapses was fully abolished 3 days after SE. Our results emphasize the role of non-NMDA-dependent synaptic plasticity changes in the processes of epileptogenesis and the potential for therapy development.