Long-term exposure to different types of chemicals is hazardous to human health. Di(2-ethylhexyl)
phthalate (
DEHP) could exert pleiotropic deleterious effects on nervous systems. Mono(2-ethylhexyl)
phthalate (
MEHP), as one of the most toxic metabolites of
DEHP, may have similar effects on nervous systems. However, no effects of
MEHP on neural circuits have been reported. To uncover the regulation of
MEHP on neural transmission, the functional changes of neural excitability and synaptic plasticity of projection neurons (PNs) have been assessed. In the current study, we recorded the action potentials (APs), stimulate action potentials (
sti-APs), mini excitement postsynaptic current (mEPSC),
calcium currents, and
sodium currents from PNs of isolated whole brain of Drosophila model utilizing patch clamp recordings. We found that MEHP-300 (at the concentration of 300 μM), but not MHEP-100 (at the concentration of 100 μM), significantly decreased the frequency and amplitude of APs. Besides, the amplitude and anti-amplitude of
sti-APs were reduced with the application of MEHP-300. Meanwhile, MEHP-300 reduced the frequency of mEPSC, but not the amplitude. Furthermore, MEHP-300 reduced the peak current densities of
sodium and
calcium channels. Therefore, our results indicated that
MEHP could alter the neural excitability and synaptic plasticity of PNs by inhibiting the
ion channels activities, revealing the potential modulation of
MEHP on neural transmission of PNs.