Intranasal Administration of Rotenone Reduces GABAergic Inhibition in the Mouse Insular Cortex Leading to Impairment of LTD and Conditioned Taste Aversion Memory

Abstract

The pesticide rotenone inhibits mitochondrial complex I and is thought to cause neurological disorders such as Parkinson’s disease and cognitive disorders. However, little is known about the effects of rotenone on conditioned taste aversion memory. In the present study, we investigated whether intranasal administration of rotenone affects conditioned taste aversion memory in mice. We also examined how the intranasal administration of rotenone modulates synaptic transmission and plasticity in layer V pyramidal neurons of the mouse insular cortex that is critical for conditioned taste aversion memory. We found that the intranasal administration of rotenone impaired conditioned taste aversion memory to bitter taste. Regarding its cellular mechanisms, long-term depression (LTD) but not long-term potentiation (LTP) was impaired in rotenone-treated mice. Furthermore, spontaneous inhibitory synaptic currents and tonic GABA currents were decreased in layer V pyramidal neurons of rotenone-treated mice compared to the control mice. The impaired LTD observed in pyramidal neurons of rotenone-treated mice was restored by a GABAA receptor agonist muscimol. These results suggest that intranasal administration of rotenone decreases GABAergic synaptic transmission in layer V pyramidal neurons of the mouse insular cortex, the result of which leads to impairment of LTD and conditioned taste aversion memory.