Hippocampal LTP shifts from NMDAR dependence to mGluR/VGCC-supported mechanisms following juvenile status epilepticus in rats.

Hippocampal long-term potentiation (LTP) can persist in the chronic epileptic state, but the mechanisms supporting this residual plasticity remain poorly understood. In particular, it is unclear whether LTP retains canonical N-methyl-D-aspartate receptor (NMDAR) dependence or shifts to alternative induction mechanisms. We addressed this question in male rats during the chronic phase following juvenile lithium-pilocarpine status epilepticus by combining behavioral assessment with field and whole-cell recordings at CA3-CA1 synapses. Despite spontaneous recurrent seizures and altered exploratory behavior, no spatial-memory impairment was detected in the Barnes maze. At CA3-CA1 synapses, LTP was reduced in magnitude but remained reliably inducible, with a markedly altered pharmacological profile. In control animals, NMDAR blockade abolished LTP, whereas combined blockade of mGluR1, mGluR5, and L-type voltage-gated calcium channels had no significant effect. After juvenile status epilepticus, by contrast, NMDAR blockade no longer affected LTP, whereas simultaneous blockade of mGluR1, mGluR5, and L-type calcium channels abolished potentiation despite unblocked NMDARs. Whole-cell recordings showed preserved voltage-dependent properties and macroscopic decay kinetics of NMDAR-mediated responses, whereas peak responses were reduced and charge transfer showed an altered pattern during repeated high-frequency stimulation after juvenile status epilepticus. Together, these findings demonstrate a persistent reorganization of hippocampal LTP induction requirements after juvenile status epilepticus and support a disease-associated metaplastic shift toward mGluR/VGCC-supported plasticity.