Abstract <p>Impaired synaptic plasticity is a hallmark of a number ofneurological disorders successfully reproduced in animal models.Short-term forms of plasticity provide dynamic regulation of synaptic efficacyin response to various patterns of neuronal activity and largelydepend on maintaining optimal conditions of the neuronal microenvironment,the key regulator of which is the blood–brain barrier (BBB). Inrecent years, the BBB has been considered an active participantin central nervous system homeostasis, and its dysfunction is recognizedas a trigger for many neurological pathologies. We have developedan in vitro protocol that mimics the early consequences of BBB dysfunctionby adapting the ionic composition of the incubation solution toblood plasma with the addition of thrombin. In the present study,we analyzed short-term synaptic plasticity in the hippocampal CA3-to-CA1networks during the early phase following modeled BBB breakdown.Data obtained reveals significant alterations in short-term synapticplasticity in the hippocampus under conditions of BBB dysfunction.We observed enhanced paired-pulse facilitation (PPF) at interstimulusintervals of 25 and 50 ms, suggesting a presynaptic locus for thechanges in neurotransmitter release. Furthermore, a significantincrease in the amplitude of post-tetanic potentiation (PTP) wasrecorded, indicating an increased reactivity of the CA3-to-CA1 neuralnetworks. The selective enhancement of the early, activity-dependentphase of plasticity following high-frequency stimulation, in theabsence of changes in the overall temporal dynamics, suggests aspecific modulation of pattern-dependent short-term plasticity inBBB pathology. Induction of seizure-like activity of hippocampalneural networks has previously been demonstrated under identicalconditions. Therefore, the present study characterizes specificalterations in synaptic properties due pathological condition formationthat may ultimately lead to long-term consequences.</p>