Medium spiny neuron

Did You Know?

• A subpopulation of MSNs contain both D1-type and D2-type receptors; in the nucleus accumbens, these mixed-type MSNs are mostly in the NAcc shell.
• Both MSN types express CB1 receptors on their somatodendritic area.
• The direct pathway of the ventral striatum mediates reward-based learning and appetitive incentive salience, while the indirect pathway mediates aversion-based learning and aversive motivational salience.

Appearance and location

Medium spiny neurons are medium-sized projection neurons with extensively branched dendrites. The cell body measures 15–18 μm and gives rise to five primary dendrites that become densely spined after the first branch point, forming nearly spherical dendritic fields 200–300 μm in diameter. About 90% of striatal neurons are MSNs; the remainder are interneurons. Direct-pathway MSNs project to the globus pallidus internal and substantia nigra pars reticulata, while indirect-pathway MSNs reach these targets via the globus pallidus external and ventral pallidum, which connect through the subthalamic nucleus.

Function

MSNs are inhibitory GABAergic neurons, yet direct-pathway MSNs excite basal ganglia output structures (e.g., thalamus) while indirect-pathway MSNs inhibit them. Cortical, thalamic, and brain-stem inputs are glutamatergic and excitatory, converging onto MSNs with vast divergence: each incoming axon contacts many MSNs, and each MSN receives input from many axons. Striatal interneurons regulate MSN excitability. Parvalbumin-expressing fast-spiking interneurons form synapses near the MSN soma, where excitatory postsynaptic potentials from dendrites must be strong enough to trigger an action potential; this proximity allows them to readily control spike generation. Other GABAergic interneurons, including those expressing tyrosine hydroxylase or neuropeptide Y, also connect with MSNs.

Dorsal striatal MSNs

The direct pathway receives excitatory input from cortex, thalamus, and other regions; its MSNs project to the globus pallidus internal or substantia nigra pars reticulata. These nuclei tonically inhibit the thalamus and motor cortex, but transient activity in direct-pathway MSNs disinhibits thalamic projections to the motor cortex, enabling movement. The indirect pathway also receives excitatory input; its MSNs project to the globus pallidus external, which tonically inhibits the subthalamic nucleus. When indirect-pathway MSNs fire, they inhibit the GPe, disinhibiting the STN; the STN then excites SNr/GPi neurons, suppressing thalamus and motor cortex activity.