Abstract: Objective To investigate the influences of extracellular acidosis on spike encoding and synaptic transmission of cortical GABAergic neurons in mice. Methods Twenty mice aged 27-30 d mice were selected to prepare coronary cortical slices and then divided into control group and extracellular acidosis group. In control group, the coronal slices were perfused with artificial cerebrospinal fluid at pH7.4, the action potential threshold potential, absolute refractory period and action potential peak spacing were recorded with the patch-clamp all-cell current clamp mode; the spontaneous excitatory postsynaptic current was recorded with the voltage clamp mode extracellular acidosis group, the artificial cerebrospinal fluid was adjusted at pH6.5, mimicking extracellular acidosis. Recorded neurons action potential and spontaneous excitatory postsynaptic currents again, comparing the difference of the above indexes between the two groups. Results Compared with the control group, the extracellular acidosis significantly prolonged the inter-spike intervals and absolute refractory periods (P<0.01)， increased the voltage of threshold potentials and the amplitude and frequency of spontaneous excitatory postsynaptic currents (P<0.01). Conclusion Extracellular acidosis leads to the dysfunction of cortical GABAergic neurons by breaking the inter-characteristics and synaptic transmission, contributing one of the possible mechanisms to acidosis-induced brain damage.