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Brain Structure and Function

, Volume 223, Issue 9, pp 3959–3973 | Cite as

Single-axon tracing of the corticosubthalamic hyperdirect pathway in primates

  • Dymka Coudé
  • André Parent
  • Martin ParentEmail author
Original Article
  • 1.2k Downloads

Abstract

Individual axons that form the hyperdirect pathway in Macaca fascicularis were visualized following microiontophoretic injections of biotinylated dextran amine in layer V of the primary motor cortex (M1). Twenty-eight singly labeled axons were reconstructed in 3D from serial sections. The M1 innervation of the subthalamic nucleus (STN) arises essentially from collaterals of long-ranged corticofugal axons en route to lower brainstem regions. Typically, after leaving M1, these large caliber axons (2–3 µm) enter the internal capsule and travel between caudate nucleus and putamen without providing any collateral to the striatum. More ventrally, they emit a thin collateral (0.5–1.5 µm) that runs lateromedially within the dorsal region of the STN, providing boutons en passant in the sensorimotor territory of the nucleus. In some cases, the medial tip of the collateral enters the lenticular fasciculus dorsally and yields a few beaded axonal branches in the zona incerta. In other cases, the collateral runs caudally and innervates the ventrolateral region of the red nucleus where large axon varicosities (up to 1.7 µm in diameter) are observed, many displaying perisomatic arrangements. Our ultrastructural analysis reveals a high synaptic incidence (141%) of cortical VGluT1-immunoreactive axon varicosities on distal dendrites of STN neurons, and on various afferent axons. Our single-axon reconstructions demonstrate that the so-called hyperdirect pathway derives essentially from collaterals of long-ranged corticofugal axons that are rarely exclusively devoted to the STN, as they also innervate the red nucleus and/or the zona incerta.

Keywords

Basal ganglia Subthalamic nucleus Primary motor cortex Single-axon reconstruction Corticosubthalamic projection Monkey 

Abbreviations

ABC

Avidine–biotin complex

AS

Associative

av

Axon varicosity

BDA

Biotinylated dextran amine

BG

Basal ganglia

bs

Brainstem

Cd

Caudate nucleus

d

Dendrite

DAB

Diaminobenzidine

DBS

Deep brain stimulation

GABA

Gamma-aminobutyric acid

Glu

Glutamate

GP

Globus pallidus

GPe

External segment of the globus pallidus (external pallidum)

GPi

Internal segment of the globus pallidus (internal pallidum)

H1

Forel’s field H1 (thalamic fasciculus)

H2

Forel’s field H2 (lenticular fasciculus)

ic

Internal capsule

LI

Limbic

M1

Primary motor cortex

PB

Phosphate buffer

PBS

Phosphate buffer saline

PD

Parkinson’s disease

PFA

Paraformaldehyde

Put

Putamen

RN

Red nucleus

rt

Reticular thalamic nucleus

SM

Sensorimotor

SN

Substantia nigra

SNr

Substantia nigra pars reticulata

SPN

Superior pontine nucleus

STN

Subthalamic nucleus

Th

Thalamus

Notes

Funding

The study was supported by research grants from the Canadian Institutes of Health Research (CIHR MOP-153068) and the Natural Sciences and Engineering Research Council of Canada (NSERC 2018-06264 and 2018-522690) to M.P. who also benefited from a Junior II career award from the Fonds de Recherche du Québec-Santé (FRQ-S). D.C. was the recipient of MSc fellowship from FRQ-S.

Compliance with ethical standards

Ethical approval

All experimental procedures were approved by the Comité de Protection des Animaux de l’Université Laval, in accordance with the Canadian Council on Animal Care’s Guide to the Care and Use of Experimental Animals (Ed2). Maximum efforts were made to minimize the number of animals used.

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.CERVO Brain Research Centre, Department of Psychiatry and Neuroscience, Faculty of MedicineUniversité LavalQuebec CityCanada

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