Astrocyte-Derived Lactate Modulates the Passive Coping Response to Behavioral Challenge in Male Mice

AbstractEvery organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism ’s actions fail to overcome the challenge. The occurrence of inactive behavior may indicate that struggling would most likely be fruitless. Repeated serious stress has been associated with mood disorders such as depression. The modulation of passive coping response patterns has been explored with a focus on the circuit level. However, the cellular and molecular mechanisms are largely uncharacterized. Here, we report that lactate is a key factor in the astrocytic modulation of the passive coping response to behavioral challenge in adult mice. We found increased extracellular lactate in the me dial prefrontal cortex (mPFC) when mice experienced the forced swimming test (FST). Furthermore, we discovered that disturbing astrocytic glycogenolysis, which is a key step for lactate production in the mPFC, decreased the duration of immobility in the FST. Knocking down monocarboxylate transporter 4 (MCT4), which is expressed exclusively in astrocytes and transports lactate from astrocytes to the extracellular space, caused similar results in the FST. The behavioral effect of both the pharmacological disturbance of astrocytic glycogenolysis and viral disruption of MCT4 expression was rescuedvia the administration ofL-lactate. Moreover, we found that both pharmacological and viral modulation of astrocyte-derived lactate in mPFC slices incr...
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research