The subthalamic nucleus (STN) is a critical excitatory signaling center within the basal ganglia circuitry. The activity of subthalamic neurons is tightly controlled by upstream inhibitory signaling centers in the basal ganglia. In this study, we used immunohistochemical techniques to firstly, visualize and quantify the STN neurochemical organization based on neuronal markers including parvalbumin (PV), calretinin (CR), SMI-32, and GAD . Secondly, we characterized the detailed regional, cellular and subcellular expression of GABA (α , α , α , β , and γ ) and GABA (R1 and R2) receptor subunits within the normal human STN. Overall, we found seven neurochemically distinct populations of principal neurons in the human STN. The three main populations detected were: (a) triple-labeled PV /CR /SMI32 ; (b) double-labeled PV /CR ; and (c) single-labeled CR neurons. Subthalamic principal neurons were found to express GABA receptor subunits α , α , β , γ , and GABA receptor subunits R1 and R2. However, no expression of GABA receptor α subunit was detected. We also found a trend of increasing regional staining intensity for all positive GABA receptor subunits from the dorsolateral pole to ventromedial extremities. The GAD interneurons showed relatively low expression of GABA receptor subunits. These results provide the morphological basis of GABAergic transmission within the normal human subthalamic nucleus and evidence of GABA innervation through both GABA and GABA receptors on subthalamic principal neurons.

The cover image, by Xi Hua Wu et al., is based on the Research Article GABAA and GABAB receptor subunit localization on neurochemically identified neurons of the human subthalamic nucleus, DOI: .