Introduction: Mechanical ventilation is a life-saving intervention in critically ill patients. However, mechanical ventilation can lead to cognitive dysfunction specially memory impairment. To explore the changes occurring in the hippocampus at the cellular level after mechanical ventilation, we assessed the synaptic currents in the CA1 region of the rat brain using the whole-cell patch clamp technique. Methodsand Materials: Male Wistar rats (250-300 gr) were divided into three study groups: 1) Control group, which did not receive any medication; 2) Anesthesia group, exposed to isoflurane for 6 hours; 3) Mechanical ventilation group, in which the rats were intubated, connected to animal ventilator, and exposed to isoflurane for 6 hours. 24 hours later, the electrophysiological characteristics of CA1 pyramidal neurons including the excitatory and inhibitory post-synaptic currents (EPSCs and IPSCs) were evaluated using the whole-cell patch clamp technique. Results: Mechanical ventilation, compared to anesthesia and control groups, reduced amplitude of evoked EPSCs (p=0.0237) and enhanced evoked IPSCs (p=0.0342) of pyramidal neurons in CA1 compared to control and anesthesia groups. Moreover, excitation/inhibition ratio across pyramidal neurons was diminished in Mechanical ventilation group compared to anesthesia and control groups (p=0.0041). No significant differences were observed in synaptic current between anesthesia and control groups. Conclusion: Our findings propose that the synaptic currents of hippocampal neurons undergo changes when mechanical ventilation is employed. This effect may potentially play a role in the development of cognitive disorders, particularly memory impairment, which are frequently observed following mechanical ventilation. Furthermore, it is important to note that these alterations are not associated with anesthesia but rather attributable to the mechanical ventilation process.