Actions and Consequences of Insulin in the Striatum

Insulin crosses the blood-brain barrier to enter the brain from the periphery. In the brain, insulin has well-established actions in the hypothalamus, as well as at the level of mesolimbic dopamine neurons in the midbrain. Notably, insulin also acts in the striatum, which shows abundant expression of insulin receptors (InsRs) throughout. These receptors are found on interneurons and striatal projections neurons, as well as on glial cells and dopamine axons. A striking functional consequence of insulin elevation in the striatum is promoting an increase in stimulated dopamine release. This boosting of dopamine release involves InsRs on cholinergic interneurons, and requires activation of nicotinic acetylcholine receptors on dopamine axons. Opposing this dopamine-enhancing effect, insulin also increases dopamine uptake through the action of insulin at InsRs on dopamine axons. Insulin acts on other striatal cells as well, including striatal projection neurons and astrocytes that also influence dopaminergic transmission and striatal function. Linking these cellular findings to behavior, striatal insulin signaling is required for the development of flavor-nutrient learning, implicating insulin as a reward signal in the brain. In this review, we discuss these and other actions of insulin in the striatum, including how they are influenced by diet and other physiological states.

Automated summary

Insulin can enter the brain from the periphery by crossing the blood-brain barrier, and it has established actions in the hypothalamus and the midbrain's mesolimbic dopamine neurons. Insulin receptors (InsRs) are abundantly expressed in the striatum, found on interneurons, striatal projection neurons, glial cells, and dopamine axons. Insulin elevation in the striatum promotes an increase in stimulated dopamine release through InsRs on cholinergic interneurons, but it also increases dopamine uptake through InsRs on dopamine axons. This striatal insulin signaling is crucial for flavor-nutrient learning and can influence dopaminergic transmission and striatal function.