Afferent projections of the subthalamic nucleus in the rat: emphasis on bilateral and interhemispheric connections

The subthalamic nucleus (STN) is important for normal movement as well as in movement disorders. The STN is a target nuclei in patients with advanced Parkinson's disease (PD). Deep brain stimulation (DBS) is a standard surgical treatment for PD. Although DBS results in a significant reduction in motor disability, several negative side effects have been reported. Thus, to understand the side effects of DBS the connection of the STN should be well known. Therefore, the present study aims to re‑examine the STN with an emphasis on poorly‑ or un‑documented connections. Furthermore, the bilateral and interhemispheric connections of the STN are evaluated. Fifteen male albino rats received injections of Fluoro‑Gold retrograde and biotinylated dextran amine anterograde tracers into the STN. Following a 7-10 day survival period, the animals were processed according to the relevant protocol for each tracer. The present study demonstrates ipsilateral connections of the STN with cortical regions (i.e., infralimbic, cingulate, frontal, piriform, primary motor, primary sensory, insular and retrosplenial cortices), the endopiriform nucleus, basal ganglia related structures (i.e., caudate putamen, globus pallidus, ventral pallidum, nucleus accumbens, claustrum and substantia innominata) and the deep cerebellar nuclei (i.e., lateral, anterior interposed). Bilateral connections of the STN were observed with limbic (amygdala, bed nucleus of stria terminalis), hypothalamic (ventromedial, posterior, anterior, lateral and mammillary) thalamic (thalamic reticular nucleus), epithalamic (habenular nucleus), and brainstem structures (superior colliculus, substantia nigra, spinal nucleus of the trigeminal nerve, red nucleus, dorsal raphe nucleus, pedunculopontine tegmental nuclei). Interhemispheric connections between left and right STN were also observed. The present study fills important gaps in connectivity of the STN. In particular, we report STN connectivity with cortical areas (i.e., piriform, endopiriform and insular), claustrum, hypothalamic, thalamic reticular, cerebellar, habenular, trigeminal, red, cuneate and gracile nuclei and substantia innominate. These connections, which have not been previously described or poorly described, provide new routes that can alter the conceptual architecture of the basal ganglia circuitry and may modify our view of the functional identity of the STN.