AbstractThe excitatory and inhibitory postsynaptic responses ofAplysiaganglion cells were elicited by either stimulating cholinergic afferent fibers or by topically applying acetylcholine (ACh) to the cell under study. The responses were evaluated as an increase in membrane conductance and compared before, during, and after perfusion with Li+‐Ringer. Excitatory postsynaptic responses were significantly depressed during 30–60 min of Li+‐Ringer perfusion. Upon return to normal Ringer, they increased sharply beyond the control, showing post‐Li+augmentation.Inhibitory postsynaptic responses were augmented during 30–60 min of Li+‐Ringer perfusion when the cells were examined before treatment with anticholinesterase. After treatment with neostigmine, however, they were found to be also depressed in Li+‐Ringer. This finding suggested a suppressing effect of Li+‐Ringer on the acetylcholinesterase (AChE) activity.The reversal potential of ACh‐induced depolarizing response was altered from the normal value of –25 mV to –5 mV during 1–2 hr of Li+‐Ringer perfusion and gradually returned to normal value in 2–3 hr after return to normal Ringer. The reversal potential of ACh‐induced hyperpolarizing response remained practically unchanged (–62 mV) during 1–2 hr of Li+‐Ringer perfusion.Post‐Li+augmentation of ACh‐induced depolarizing responses was explained by an increase in driving force for Na+movement resulting from a depletion of intracellular Na+. The systematic shift of the dose‐response curves during Li+‐Ringer perfusion suggested that the affinities of both excitatory and inhibitory receptors to ACh are depressed and the ef