Anterograde Tracing From the Göttingen Minipig Motor and Prefrontal Cortex Displays a Topographic Subthalamic and Striatal Axonal Termination Pattern Comparable to Previous Findings in Primates

Background: Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) is a validated neurosurgical treatment of Parkinson’s Disease (PD). To investigate the mechanism of action, including potential DBS induced neuroplasticity, we have previously used a minipig model of Parkinson’s Disease...

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Autores principales: Johannes Bech Steinmüller, Carsten Reidies Bjarkam, Dariusz Orlowski, Jens Christian Hedemann Sørensen, Andreas Nørgaard Glud
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:53e9f92bfc2742bf82b5c2697e3870b72021-12-01T07:02:38ZAnterograde Tracing From the Göttingen Minipig Motor and Prefrontal Cortex Displays a Topographic Subthalamic and Striatal Axonal Termination Pattern Comparable to Previous Findings in Primates1662-511010.3389/fncir.2021.716145https://doaj.org/article/53e9f92bfc2742bf82b5c2697e3870b72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncir.2021.716145/fullhttps://doaj.org/toc/1662-5110Background: Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) is a validated neurosurgical treatment of Parkinson’s Disease (PD). To investigate the mechanism of action, including potential DBS induced neuroplasticity, we have previously used a minipig model of Parkinson’s Disease, although the basal ganglia circuitry was not elucidated in detail.Aim: To describe the cortical projections from the primary motor cortex (M1) to the basal ganglia and confirm the presence of a cortico-striatal pathway and a hyperdirect pathway to the subthalamic nucleus, respectively, which is known to exist in primates.Materials and Methods: Five female Göttingen minipigs were injected into the primary motor cortex (n = 4) and adjacent prefrontal cortex (n = 1) with the anterograde neuronal tracer, Biotinylated Dextran Amine (BDA). 4 weeks later the animals were sacrificed and the brains cryosectioned into 30 μm thick coronal sections for subsequent microscopic analysis.Results: The hyperdirect axonal connections from the primary motor cortex were seen to terminate in the dorsolateral STN, whereas the axonal projections from the prefrontal cortex terminated medially in the STN. Furthermore, striatal tracing from the motor cortex was especially prominent in the dorsolateral putamen and less so in the dorsolateral caudate nucleus. The prefrontal efferents were concentrated mainly in the caudate nucleus and to a smaller degree in the juxtacapsular dorsal putamen, but they were also found in the nucleus accumbens and ventral prefrontal cortex.Discussion: The organization of the Göttingen minipig basal ganglia circuitry is in accordance with previous descriptions in primates. The existence of a cortico-striatal and hyperdirect basal ganglia pathway in this non-primate, large animal model may accordingly permit further translational studies on STN-DBS induced neuroplasticity of major relevance for future DBS treatments.Johannes Bech SteinmüllerJohannes Bech SteinmüllerJohannes Bech SteinmüllerCarsten Reidies BjarkamDariusz OrlowskiDariusz OrlowskiJens Christian Hedemann SørensenJens Christian Hedemann SørensenAndreas Nørgaard GludAndreas Nørgaard GludFrontiers Media S.A.articlebasal gangliahyperdirect pathwaymotor cortexneuronal tracingprefrontal cortexstriatumNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neural Circuits, Vol 15 (2021)
institution DOAJ
collection DOAJ
language EN
topic basal ganglia
hyperdirect pathway
motor cortex
neuronal tracing
prefrontal cortex
striatum
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle basal ganglia
hyperdirect pathway
motor cortex
neuronal tracing
prefrontal cortex
striatum
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Johannes Bech Steinmüller
Johannes Bech Steinmüller
Johannes Bech Steinmüller
Carsten Reidies Bjarkam
Dariusz Orlowski
Dariusz Orlowski
Jens Christian Hedemann Sørensen
Jens Christian Hedemann Sørensen
Andreas Nørgaard Glud
Andreas Nørgaard Glud
Anterograde Tracing From the Göttingen Minipig Motor and Prefrontal Cortex Displays a Topographic Subthalamic and Striatal Axonal Termination Pattern Comparable to Previous Findings in Primates
description Background: Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) is a validated neurosurgical treatment of Parkinson’s Disease (PD). To investigate the mechanism of action, including potential DBS induced neuroplasticity, we have previously used a minipig model of Parkinson’s Disease, although the basal ganglia circuitry was not elucidated in detail.Aim: To describe the cortical projections from the primary motor cortex (M1) to the basal ganglia and confirm the presence of a cortico-striatal pathway and a hyperdirect pathway to the subthalamic nucleus, respectively, which is known to exist in primates.Materials and Methods: Five female Göttingen minipigs were injected into the primary motor cortex (n = 4) and adjacent prefrontal cortex (n = 1) with the anterograde neuronal tracer, Biotinylated Dextran Amine (BDA). 4 weeks later the animals were sacrificed and the brains cryosectioned into 30 μm thick coronal sections for subsequent microscopic analysis.Results: The hyperdirect axonal connections from the primary motor cortex were seen to terminate in the dorsolateral STN, whereas the axonal projections from the prefrontal cortex terminated medially in the STN. Furthermore, striatal tracing from the motor cortex was especially prominent in the dorsolateral putamen and less so in the dorsolateral caudate nucleus. The prefrontal efferents were concentrated mainly in the caudate nucleus and to a smaller degree in the juxtacapsular dorsal putamen, but they were also found in the nucleus accumbens and ventral prefrontal cortex.Discussion: The organization of the Göttingen minipig basal ganglia circuitry is in accordance with previous descriptions in primates. The existence of a cortico-striatal and hyperdirect basal ganglia pathway in this non-primate, large animal model may accordingly permit further translational studies on STN-DBS induced neuroplasticity of major relevance for future DBS treatments.
format article
author Johannes Bech Steinmüller
Johannes Bech Steinmüller
Johannes Bech Steinmüller
Carsten Reidies Bjarkam
Dariusz Orlowski
Dariusz Orlowski
Jens Christian Hedemann Sørensen
Jens Christian Hedemann Sørensen
Andreas Nørgaard Glud
Andreas Nørgaard Glud
author_facet Johannes Bech Steinmüller
Johannes Bech Steinmüller
Johannes Bech Steinmüller
Carsten Reidies Bjarkam
Dariusz Orlowski
Dariusz Orlowski
Jens Christian Hedemann Sørensen
Jens Christian Hedemann Sørensen
Andreas Nørgaard Glud
Andreas Nørgaard Glud
author_sort Johannes Bech Steinmüller
title Anterograde Tracing From the Göttingen Minipig Motor and Prefrontal Cortex Displays a Topographic Subthalamic and Striatal Axonal Termination Pattern Comparable to Previous Findings in Primates
title_short Anterograde Tracing From the Göttingen Minipig Motor and Prefrontal Cortex Displays a Topographic Subthalamic and Striatal Axonal Termination Pattern Comparable to Previous Findings in Primates
title_full Anterograde Tracing From the Göttingen Minipig Motor and Prefrontal Cortex Displays a Topographic Subthalamic and Striatal Axonal Termination Pattern Comparable to Previous Findings in Primates
title_fullStr Anterograde Tracing From the Göttingen Minipig Motor and Prefrontal Cortex Displays a Topographic Subthalamic and Striatal Axonal Termination Pattern Comparable to Previous Findings in Primates
title_full_unstemmed Anterograde Tracing From the Göttingen Minipig Motor and Prefrontal Cortex Displays a Topographic Subthalamic and Striatal Axonal Termination Pattern Comparable to Previous Findings in Primates
title_sort anterograde tracing from the göttingen minipig motor and prefrontal cortex displays a topographic subthalamic and striatal axonal termination pattern comparable to previous findings in primates
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/53e9f92bfc2742bf82b5c2697e3870b7
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