Serotonin regulation of subthalamic neurons

The subthalamic nucleus (STN) is a key component of the basal ganglia. As the only basal ganglia nucleus comprised of mostly glutamatergic neurons, STN neurons provide a key driving force to their target neurons. Thus, regulation of STN neuron activity is important. One STN regulator is the serotonin (5-HT) system. The STN receives a dense 5-HT innervation. 5-HT1A, 5-HT1B, 5-HT2C, and 5-HT4 receptors are expressed in the STN. 5-HT may regulate the STN via several mechanisms. First, 5-HT may affect STN neuron excitability directly by either inhibiting a subpopulation of STN neurons via activation of 5-HT1A receptors or exciting STN neurons through activation of 5-HT2C and 5-HT4 receptors. Second, 5-HT may affect synaptic inputs to the STN. Via activation of 5-HT1B receptors on the afferent terminals, 5-HT inhibits glutamatergic input to the STN, but the inhibitory effect on GABAergic input is smaller. Third, 5-HT may regulate the STN glutamatergic output by activating presynaptic 5-HT1B receptors, thus reducing burst firing in target neurons. Last, 5-HT may affect glutamate release at the intra-STN axon collaterals and regulate the recurrent excitation. These mechanisms may work in concert to fine-tune the intensity and pattern of STN activity and reduce STN output bursts.