Medium spiny neuron

Medium spiny neurons (MSNs), also known as spiny projection neurons (SPNs), are a special type of GABAergic inhibitory cell representing 95% of neurons within the human striatum, a basal ganglia structure. Medium spiny neurons have two primary phenotypes (characteristic types): D1-type MSNs of the direct pathway and D2-type MSNs of the indirect pathway. Most striatal MSNs contain only D1-type or D2-type dopamine receptors, but a subpopulation of MSNs exhibit both phenotypes.

Direct pathway MSNs excite their ultimate basal ganglia output structure (such as the thalamus) and promote associated behaviors; these neurons express D1-type dopamine receptors, adenosine A1 receptors, dynorphin peptides, and substance P peptides. Indirect pathway MSNs inhibit their output structure and in turn inhibit associated behaviors; these neurons express D2-type dopamine receptors, adenosine A2A receptors (A2A), DRD2–A2A heterotetramers, and enkephalin. Both types express glutamate receptors (NMDAR and AMPAR), cholinergic receptors (M1 and M4) and CB1 receptors are expressed on the somatodendritic area of both MSN types. A subpopulation of MSNs contain both D1-type and D2-type receptors, with approximately 40% of striatal MSNs expressing both DRD1 and DRD2 mRNA. In the nucleus accumbens (NAcc), these mixed-type MSNs that contain both D1-type and D2-type receptors are mostly contained in the NAcc shell.

The dorsal striatal MSNs play a key role in initiating and controlling movements of the body, limbs, and eyes. The ventral striatal MSNs play a key role in motivation, reward, reinforcement, and aversion. Dorsal and ventral medium spiny neuron subtypes (i.e., direct D1-type and indirect D2-type) are identical phenotypes, but their output connections differ.