Striatal Medium Spiny Neurons Terminate in a Distinct Region in the Lateral Hypothalamic Area and Do Not Directly Innervate Orexin/Hypocretin- or Melanin-Concentrating Hormone-Containing Neurons

Neuronal circuits including medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and melanin-concentrating hormone (MCH)-containing neurons in the lateral hypothalamic area (LHA) are hypothesized to play an important role in hedonic feeding. A reciprocal connection between NAc MSNs and MCH-containing neurons is proposed to form a neuronal circuit that is involved in hedonic feeding. Although NAc MSNs have been shown to receive projection from MCH-containing neurons, it is not known whether MCH-containing neurons in the LHA also receive direct inputs from NAc MSNs. Here, we developed a genetic approach that allows us to visualize almost all striatal MSNs including NAc MSNs. We demonstrate that striatal MSNs terminate in a distinct region within the anterior LHA, and that the terminal area of striatal MSNs in this region contains glutamatergic neurons and is distinctly separate from orexin/hypocretin- or MCH-containing neurons. These observations suggest that NAc MSNs do not directly innervate MCH-containing neurons, but may indirectly signal MCH-containing neurons via glutamatergic neurons in the anterior LHA.