Intracellular recordings of jejunal myenteric neurons with an afterspike hyperpolarization (AH) fromTrichinella spiralis-infected animals showed enhanced excitability on days 3, 6, and 10postinfection (PI) compared with uninfected animals. Lower membrane potential, increased membrane input resistance, decreased threshold for action potential discharge, decreased AH amplitude and duration, and increased fast excitatory postsynaptic potential amplitude and duration were characteristic of neuronal recordings from infected animals. Concurrent with electrophysiological changes duringT. spiralis infection, increased cytochrome oxidase activity, a marker of neuronal metabolic activity, and the expression of nuclear c-Fos immunoreactivity, an indicator of transcriptional-translational activity, were also observed in myenteric ganglion cells. Double-labeling for calbindin-immunoreactive myenteric neurons revealed that ∼50% of these neurons also expressed increased c-Fos immunoreactivity duringT. spiralis infection. Myeloperoxidase activity was significantly higher in the jejunum of T. spiralis-infected guinea pigs on days 3, 6, and 10 PI vs. uninfected counterparts. The expression of c-Fos in calbindin-immunoreactive neurons together with enhanced neuronal electrical and metabolic activity during nematode-induced intestinal inflammation suggests the onset of excitation-transcription coupled changes in enteric neural microcircuits.