ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
This article is part of the Research TopicThe Role of Cellular Subtypes in Striatal ActivityView all 5 articles
Matrix-biased excitatory and inhibitory inputs to the striatum involving external segment of the globus pallidus
Provisionally accepted
- 1Hokkaido University, Sapporo, Japan
- 2Hokkaido Daigaku, Sapporo, Japan
- 3National Institute for physiological sciences, Okazaki, Japan
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In the basal ganglia, the external segment of the globus pallidus (GPe) interconnects with the subthalamic nucleus (STN), forming the indirect pathway. In addition, a subpopulation of GPe neurons projects exclusively to the striatum. Here, we demonstrated that GPe axons within the striatum exhibit a strong bias toward the matrix compartment in rats. Using a combination of retrograde adeno-associated viral (AAV) vectors and Cre-dependent fluorescent protein expression, we found that this biased projection arises from both GPe neurons targeting the STN and those projecting to the striatum. In contrast, striatal projections to the GPe originate from both matrix and striosome compartments. Whole-cell patch-clamp recordings revealed that optogenetic stimulation of GPe axons elicited inhibitory postsynaptic currents (IPSCs) in both medium spiny neurons (MSNs) and cholinergic interneurons (CINs) within the matrix. Recordings using cesium-based pipette solution showed increased connection probability in MSNs compared to potassium-based solution, suggesting distal synaptic contacts. In contrast, anatomical observation revealed that GPe axons frequently formed proximal appositions to the somata and proximal dendrites of CINs. For excitatory inputs, motor cortical areas and ventral thalamic nuclei—components of the basal ganglia motor loop— also preferentially targeted the matrix compartment. Moreover, these thalamic nuclei elicited EPSCs in GPe neurons, indicating functional synaptic connections. Finally, intersectional labeling of striatal neurons and GPe neurons innervated by ventral thalamic nuclei revealed a spatial overlap between striatal neurons and GPe axons within the striatal subregions. These findings suggest that convergent cortical and thalamic excitation of both the striatum and GPe may trigger feedforward inhibition within the striatal matrix compartment, particularly onto CINs. This mechanism may contribute to the fine-tuning of striatal output in motor-related basal ganglia circuits.
Keywords: external segment of globus pallidus (GPe), Striatum, cholinergic interneurons, Matrix, striosome
Received: 16 Sep 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Karube, Kobayashi and Fujiyama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Fuyuki Karube, karube@med.hokudai.ac.jp
Fumino Fujiyama, fujiyama@pop.med.hokudai.ac.jp
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