Biased thalamic innervation onto the distinct subregion where dopamine receptor 1 is dominantly expressed in the caudal striatum

Abstract

In the ventral part of the caudal striatum, the direct and indirect pathway neurons are unevenly distributed, forming zones with a paucity of neurons with dopamine receptor 1 (D1R) or dopamine receptor 2 (D2R), referred as D1R- or D2R-poor zone (D1pz or D2pz, respectively). This contrasts with their uniform distribution in other striatal regions. A key question is whether D1pz and D2pz function as a unit or independently. Since the striatum requires afferent excitatory inputs for activation, investigating biased excitatory inputs to the caudal striatum is essential. Our findings indicate that vesicular glutamate transporter 2 (VGluT2) was concentrated in D2pz, suggesting biased excitatory innervation. Retrograde tracer labeling identified potential sources of subcortical glutamatergic projections. Projection from the paraventricular nucleus of the thalamus (PVT) was visualized using VGluT2-Cre mice. PVT preferentially projected to the ventral caudal region in the striatum. Quantitative analysis of PVT axons revealed preferential localization in the D2pz, with fewer axons in the D1pz. The substantia nigra pars lateralis, innervated by the caudal striatum, did not project to the PVT, suggesting the caudal striatum and PVT may not form a part of the cortico-basal ganglia-thalamic loop. These results imply that D1pz and D2pz may be differentially activated by PVT inputs, selectively recruiting direct pathways.

Keywords: VGluT2; basal ganglia; direct pathway; dopamine receptor; paraventricular nucleus of the thalamus; striatum.