Abstract <p>Temporal lobe epilepsy (TLE) is associated with cognitivedecline and pharmacoresistance, processes believed to stem frommaladaptive synaptic plasticity in the hippocampus. However, whethersuch maladaptation depletes the synaptic plasticity reserve in chronicepilepsy, leading to neural network rigidity, remains unclear. Here,we used the lithium-pilocarpine model in rats to study excitatorytransmission at hippocampal CA3-CA1 synapses during the chronic phase(30–34 days post-status epilepticus). Field potential recordingsfrom brain slices of epileptic rats revealed a marked impairment(~50% reduction) in basal synaptic transmission compared to controls. Despitethis deficit, an initial challenge with an epileptogenic solution(elevated [K⁺]_o,low [Mg²⁺]_o, 100µM 4-aminopyridine) induced robust synaptic potentiation of similarmagnitude in both groups, evidenced by large effect sizes (Control:Cohen’s <i>d</i> ≈ 2.20; Epilepsy: <i>d</i> ≈ 1.70). A second epileptiform challengefurther potentiated control slices (<i>d</i> ≈0.71) but failed to do so in slices from epileptic rats (<i>d</i> ≈ 0.14). These results demonstratethat the chronic epileptic hippocampus retains a capacity for synaptic potentiationagainst a background of low baseline transmission, yet this plasticityreserve is rapidly depleted. The failure to potentiate upon recurrent challengesindicates a depletion of the synaptic plasticity reserve in chronicTLE, suggesting a mechanism underlying network rigidity and disease progression.</p>