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Single-axon tracing of the corticosubthalamic hyperdirect pathway in primates

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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.

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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

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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.

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  1. CERVO Brain Research Centre, Department of Psychiatry and Neuroscience, Faculty of Medicine, Université Laval, 2601, Canardière, Room F-6500, Quebec City, QC, G1J 2G3, Canada

    Dymka Coudé, André Parent & Martin Parent

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  1. Dymka Coudé
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  2. André Parent
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  3. Martin Parent
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Correspondence to Martin Parent.

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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.

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Coudé, D., Parent, A. & Parent, M. Single-axon tracing of the corticosubthalamic hyperdirect pathway in primates. Brain Struct Funct 223, 3959–3973 (2018). https://doi.org/10.1007/s00429-018-1726-x

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