Glycolysis inhibition partially resets epilepsy-induced alterations in the dorsal hippocampus-basolateral amygdala circuit involved in anxiety-like behavior.

Pharmacoresistant temporal lobe epilepsy affects millions of people around the world with uncontrolled seizures and comorbidities, like anxiety, being the most problematic aspects calling for novel therapies. The intrahippocampal kainic acid model of temporal lobe epilepsy is an appropriate rodent model to evaluate the effects of novel interventions, including glycolysis inhibition, on epilepsy-induced alterations. Here, we investigated kainic acid-induced changes in the dorsal hippocampus (dHPC) and basolateral amygdala (BLA) circuit and the efficiency of a glycolysis inhibitor, 2-deoxy D-glucose (2-DG), in resetting such alterations using simultaneous local field potentials (LFP) recording and elevated zero-maze test. dHPC theta and gamma powers were lower in epileptic groups, both in the baseline and anxiogenic conditions. BLA theta power was higher in baseline condition while it was lower in anxiogenic condition in epileptic animals and 2-DG could reverse it. dHPC-BLA coherence was altered only in anxiogenic condition and 2-DG could reverse it only in gamma frequency. This coherence was significantly correlated with the time in which the animals exposed themselves to the anxiogenic condition. Further, theta-gamma phase-locking was lower in epileptic groups in the dHPC-BLA circuit and 2-DG could considerably increase it.