Diabetic encephalopathy causes the imbalance of neural activities between hippocampal glutamatergic neurons and GABAergic neurons in mice

•We studied the hyperglycemia-induced imbalance of two different types of hippocampal neurons in brain during diabetic encephalopathy.•We used a single high-dose intraperitoneal injection of STZ to induce diabetes mice model.•We used C57 Thy1-YFP/GAD67-GFP mice to analyze cell-specific mechanisms of diabetic encephalopathy underlying.•Diabetes mellitus (DM) mice exhibited significantly impaired in spatial learning and memory with MWM training.•The influences on spike encoding were different at glutamatergic and GABAergic neurons, moreover the function of GABAergic synapses decreased and glutamatergic synapses increased during DM. Diabetic encephalopathy is a severe diabetes-related complication in the central nervous system (CNS) that is characterized by the impairment of neurochemical and structural changes leading to cognitive dysfunction. Its cellular and molecular mechanisms are still unclear and clinical approaches are still lacking of promising therapies. In this study, we have investigated the changes of different hippocampal neurons during diabetic encephalopathy in mouse models of diabetes by simultaneously analyzing the activities and synaptic transmission of glutamatergic neurons and GABAergic neurons in brain slices. Compared with the data from a group of control, diabetic encephalopathy permanently impairs the excitability of GABAergic neurons and synaptic transmission mediated by γ-aminobutyric acid (GABA). However, glutamatergic neurons appear to be more excited. Our findings highlight the critical role of the dysfunction of GABAergic neurons and glutamatergic neurons during diabetic encephalopathy in hippocampus to neural impairment as well as a strategy to prevent the function of progress of diabetic encephalopathy by protecting central neurons.