Cortico-subthalamic inputs from the motor, limbic, and associative areas in normal and dopamine-depleted rats are not fully segregated

Abstract

The subthalamic nucleus (STN) receives monosynaptic glutamatergic afferents from different areas of the cortex, known as the "hyperdirect" pathway. The STN has been divided into three distinct subdivisions, motor, limbic, and associative parts in line with the concept of parallel information processing. The extent to which the parallel information processing coming from distinct cortical areas overlaps in the different territories of the STN is still a matter of debate and the proposed role of dopaminergic neurons in maintaining the coherence of responses to cortical inputs in each territory is not documented. Using extracellular electrophysiological approaches, we investigated to what degree the motor and non-motor regions in the STN are segregated in control and dopamine (DA) depleted rats. We performed electrical stimulation of different cortical areas and recorded STN neuronal responses. We showed that motor and non-motor cortico-subthalamic pathways are not fully segregated, but partially integrated in the rat. This integration was mostly present through the indirect pathway. The spatial distribution and response latencies were the same in sham and 6-hydroxydopamine lesioned animals. The inhibitory phase was, however, less apparent in the lesioned animals. In conclusion, this study provides the first evidence that motor and non-motor cortico-subthalamic pathways in the rat are not fully segregated, but partially integrated. This integration was mostly present through the indirect pathway. We also show that the inhibitory phase induced by GABAergic inputs from the external segment of the globus pallidus is reduced in the DA-depleted animals.

A glimpse at deep brain stimulation mechanisms using subthalamic nucleus optogenetic manipulations

“…enforces the idea that in rat territories are highly intertwined and the STN represents a site of convergence for numerous cortical projections, as suggested by former studies (42,43).…”

Deep brain stimulation: current challenges and future directions

“…These brain regions are not connected directly, but high-frequency stimulation nevertheless uncovered a high level of functional connectivity. Furthermore, electrical stimulation approaches have demonstrated that individual STN neurons receive input from motor and limbic areas53. In this way, two distinct behavioural modalities, motion and emotion, can converge, which explains some of the mixed clinical effects of DBS.…”

Stimulation of Cortico-Subthalamic Projections Amplifies Resting Motor Circuit Activity and Leads to Increased Locomotion in Dopamine-Depleted Mice

“…The subthalamic nucleus (STN), the sole glutamatergic nucleus in the basal ganglia, is in a unique and powerful position to influence the processing of motor information. The STN receives glutamatergic inputs from multiple areas of the cortex ( Petreanu et al, 2009 ; Janssen et al, 2016 ), and is located at the crux of two primary basal ganglia pathway outputs (indirect and hyperdirect, Smith et al, 1998 ; Nambu et al, 2002 ).…”