Striatal astrocytes modulate behavioral flexibility and whole-body metabolism in mice.

Brain circuits in reward-associated behaviors are potent drivers of feeding behavior but also recently emerged as regulator of metabolism. Short or chronic exposures to caloric food alter brain structures and are associated with increased astrocytes reactivity and pro-inflammatory responses in both mice and humans. However, the role of striatal astrocytes in regulating adaptive and maladaptive behavioral and metabolic responses to energy-dense food remains elusive. In this study we reveal that chemogenetic manipulation of the astrocytes in striatal structures can exert a direct effect on peripheral metabolism in male mice, and that manipulation of astrocytes in the dorsal striatum can alter peripheral metabolism and is sufficient to restore cognitive deficit induced by chronic high fat high sucrose (HFHS) diet exposure in obese mice. Altogether, this work reveals a yet unappreciated role for striatal astrocytes as a direct operator of flexible behavior and metabolic control.