Compartmental origins of striatal efferent projections in the cat

doi:10.1016/0306-4522(89)90080-8

Neuroscience

Volume 32, Issue 2, 1989, Pages 297-321

https://doi.org/10.1016/0306-4522(89)90080-8 Get rights and content

Abstract

Injections of the retrograde tracer, wheat germ agglutinated-horseradish peroxidase were placed in the substantia nigra, in adjoining dopamine-containing cell groups A8 and A10, and in the internal and external parts of the pallidal complex of 20 cats in order to identify the compartmental origins of striatal efferent projections to the pallidum and midbrain. Patterns of retrograde cell-labeling in the caudate nucleus were analysed with respect to its striosomal architecture as detected in sections stained for acetylcholinesterase. Where possible, a similar compartmental analysis of cell-labeling in the putamen was also carried out. In 15 cats anterograde labeling in the striatum was studied in the sections stained with wheat germ agglutinated-horseradish peroxidase or in autoradiographically treated sections from cases in which [³⁵S]methionine was mixed with the wheat germ agglutinated-horseradish peroxidase in the injection solution.

Predominant labeling of projection neurons lying in striosomes (usually with some labeling of dorso-medial matrix neurons) occurred in a subset of the cases of nigral injection, including all cases (n = 9) in which the injection sites were centered in the densocellular zone of the substantia nigra pars compacta [Jiménez-Castellanos J. and Graybiel A.M. (1987) Neuroscience23, 223–242.] Dense labeling of neurons in the extrastriosomal matrix, with at most sparse labeling of striosomal neurons, occurred in all cases of pallidal injection (n = 8) and in two cases of nigral injection in which the injection sites were lateral and anterior to the densocellular zone. Mixed labeling of striosomal and matrical neurons occurred in a third group of cases in which the injection sites were lateral to the densocellular zone but close to it. In a single case with an injection site situated in the pars lateralis of the substantia nigra, there was preferential labeling of striosomal neurons in the caudal caudate nucleus but widespread labeling of neurons in both striosomes and matrix in the putamen.

A second type of compartmental ordering of projection neurons was found in the extrastriosomal matrix of the striatum. In cases of pallidal and nigral injection, there were gaps in cell labeling that did not match striosomes precisely, and often clusters of labeled cells appeared that did not correspond to acetylcholin-esterase-poor striosomes but, instead, to patches of matrix. Especially prominent were clusters beside striosomes. There was a topographic ordering of striatal projection neurons both in the striosomes and in the extrastriosomal matrix according to their dorsoventral and latitudinal positions.

Intranigral injections of [³⁵S]methionine mixed with wheat germ agglutinated-horseradish peroxidase, and nigral cases in which anterograde and retrograde labeling with wheat germ agglutinated-horseradish peroxidase were differentiable, demonstrated patterns of conjoint anterograde and retrograde labeling of corresponding striosomes or of corresponding extrastriosomal matrix. These findings suggest the presence of reciprocal links between the striatum and the substantia nigra pars compacta, or at least links between the striatum and parts of the pars compacta and pars reticulata lying very close to one another. By contrast, injections centered in cell group A8 elicited very little retrograde labeling in either the dorsal or the ventral striatum, and although injections placed in the ventral tegmental area led to extensive retrograde labeling of parts of the ventral striatum, there was little retrograde labeling of the dorsal striatum. Thus the projections from cell groups A8 and A10 to the dorsal striatum may only be weakly reciprocated, if at all.

We conclude the following:

(1)
Striosomal ordering is followed by each major category of striatal efferent connection, but non-striosornal ordering of striatal projection neurons also occurs.
(2)
The extrastriosomal matrix of the striatum is specialized for conveying information to the two segments of the globus pallidus and the lateral (probably reticular) part of the substantia nigra.
(3)
Within the matrix, neurons projecting to the pallidum and to the substantia nigra are subject to a form of non-striosomal but striosome-like compartmentalization.
(4)
The striosomal system of the striatum is specialized for transmitting information from the striatum to the substantia nigra, though a small striosomal output to the pallidum is not excluded by these findings.
(5)
Cell group A9 may participate in reciprocating striatonigral-nigrostriatal loops, but the projections from cell groups A8 and A10 to the dorsal striatum may lack strong direct return connections.

References (90)

BeachT.G. et al.
The distribution of substance P in the primate basal ganglia: an immunohistochemical study of the baboon and human brain
Neuroscience
(1984)
BecksteadR.M.
Striatal substance P cell clusters coincide with the high density terminal zones of the discontinuous nigrostrial dopaminergic projection system in the cat. A study by combined immunohistochemistry and autoradiographic axon tracing
Neuroscience
(1987)
BecksteadR.M. et al.
Striatal axons to the globus pallidus, entopeduncular nucleus and substantia nigra come mainly from separate cell populations in cat
Neuroscience
(1986)
BessonM.-J. et al.
[3H]-SCH23390 binding to D1 dopamine receptors in the basal ganglia of the cat and primate: delineation of striosomal compartments and pallidal and nigral subdivisions
Neuroscience
(1988)
BolamJ.P. et al.
Cellular substrates of the histochemically-defined striosome/matrix system of the caudate nucleus: a combined Golgi and immunocytochemical study in rat and ferret
Neuroscience
(1988)
ChesseletM.-F. et al.
Striatal neurons expressing somatostatin-like immunoreactivity: evidence for a peptidergic interneuronal system in the cat
Neuroscience
(1986)
CowanW.M. et al.
The autoradiographic demonstration of axonal connections in the central nervous system
Brain Res.
(1972)
FaullR.L.M. et al.
The disturbance of neurotensin receptors and acetylcholinesterase in the human caudate nucleus: evidence for the existence of a third neurochemical compartment
Brain Res.
(1989)
GraybielA.M.
Compartmental organization of the mammalian striatum
GraybielA.M. et al.
Fiber connections of the basal ganglia

HaberS.N. et al.

Correlation between met-enkephalin and substance P immunoreactivity in the primate globus pallidus

Neuroscience

(1981)

HerkenhamM. et al.

Cell clusters in the nucleus accumbens of the rat, and the mosaic relationship of opiate receptors, acetylcholinesterase and subcortical afferent terminals

Neuroscience

(1984)

IllingR.B. et al.

Visualization of the HRP reaction product using the polarization microscope

Neurosci. Lett.

(1979)

Jiménez-CastellanosJ. et al.

Subdivisions of the dopamine-containing A8-A9-A10 complex identified by their differential mesostriatal innervation of striosomes and extrastriosomal matrix

Neuroscience

(1987)

KalilK.

Patch-like termination of thalamic fibres in the putamen of the rhesus monkey: an autoradiographic study

Brain Res.

(1978)

LoopuijtL.D. et al.

Organization of the striatum: collateralization of its efferent axons

Brain Res.

(1985)

NautaW.J.H. et al.

The anatomy of the extrapyramidal system

NautaW.J.H. et al.

Projections of the lentiform nuclei in the monkey

Brain Res.

(1966)

NautaW.J.H. et al.

Efferent connections and nigral afferents of the nucleus accumbens septi in the rat

Neuroscience

(1978)

NiimiK. et al.

Efferent projections of the head of the caudate nucleus in the cat

Brain Res.

(1970)

ParentA. et al.

The striatopallidal and striatonigral projections: two distinct fiber systems in primate

Brain Res.

(1984)

RagsdaleC.W. et al.

The fronto-striatal projection in the cat and monkey and its relationship to inhomogeneities established by acetylcholinesterase histochemistry

Brain Res.

(1981)

RoyceG.J.

Autoradiographic evidence for a discontinuous projection to the caudate nucleus from the centromedian nucleus in the cat

Brain Res.

(1978)

RusschenF.T. et al.

The amygdalostriatal projections in monkey. An anterograde tracing study

Brain Res.

(1985)

SomogyiP. et al.

Monosynaptic input from the nucleus accumbens-ventral striatum region to retrogradely labelled nigrostriatal neurones

Brain Res.

(1981)

SzaboJ.

Topical distribution of the striatal efferents in the monkey

Expl Neurol.

(1962)

SzaboJ.

The efferent projections of the putamen in the monkey

Expl Neurol.

(1967)

Van der KooyD. et al.

Neuronal birthdate underlies the development of striatal compartments

Brain Res.

(1987)

AlexanderG.E. et al.

Parallel organization of functionally segregated circuits linking basal ganglia and cortex

BecksteadR.M. et al.

Immunohistochemical demonstration of differential substance P, metenkephalin, and glutamic acid decarboxylase containing cell body and axon distributions in the corpus striatum of the cat

J. comp. Neurol.

(1985)

BessonM.-J. et al.

Patterns of coexistence of neuropeptides and glutamic acid decarboxylase in neurons of the feline striatum

Soc. Neurosci. Abstr.

(1988)

BessonM.-J. et al.

Patterns of coexistence of neuropeptides: substance P, dynorphin B, and glutamic acid decarboxylase in neurons of the cat caudate nucleus

(1989)

BunneyB.S. et al.

The precise location of nigral afferents in the rat as determined by a retrograde tracing technique

Brain Res.

(1975)

ChesseletM.-F. et al.

In situ hybridization of mRNAs for GAD, tyrosine hyroxylase and tachykinins in the basal ganglia

Soc. Neurosci. Abstr.

(1986)

CowanW.M. et al.

Strio-pallidal projections in the monkey

J. Neurol. Neurosurg. Neuropsychiat.

(1966)

DonoghueJ.P. et al.

Neostriatal projections from individual cortical fields conform to histochemically distinct striatal compartments in the rat

Brain Res.

(1986)

FeigenbaumL.A. et al.

Heterogeneous striatal afferent connections from distinct regions of the dopamine-containing midbrain of the primate

Soc. Neurosci. Abstr.

(1988)

FillouxF.M. et al.

Presynaptic and postsynaptic D1 dopamine receptors in the nigro-striatal system of the rat brain: a quantitative autoradiographic study using the selective Dl antagonist [3H] SCH 23390

Brain Res.

(1987)

FishellG. et al.

Development of the striatonigral pathway reveals a possible mechanism of striatal compartmentalization

Soc. Neurosci. Abstr.

(1985)

FoxC.A. et al.

The spiny neurons in the primate striatum: a Golgi and electron microscopic study

J. Hirnforsch.

(1971)

FoxC.A. et al.

The aspiny neurons and the glia in the primate striatum: a Golgi and electron microscopic study

J. Hirnforsch.

(1971)

Geneser-JensenF.A. et al.

Distribution of acetylcholinesterase in the hippocampal region of the guinea pig

Z. Zellforsch Mikrosk. Anat.

(1971)

GerfenC.R.

The neostriatal mosaic: relationships among striatal input, output and peptidergic system

Nature

(1984)

GerfenC.R.

The neostriatal mosaic. I. Compartmental organization of projections from the striatum to the substantia nigra in the rat

J. comp. Neurol.

(1985)

GerfenC.R. et al.

The neostriatal mosiac: compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey

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Search strategy and selection criteria
References for this article were identified through searches in PubMed with the search terms « dystonia », « dopamine”, « striatum », « basal ganglia », « imaging data », « animal model », « procedural learning », « pathophysiology », and « plasticity » from 1998 until 2018. Articles were also identified through searches of the authors' own files. Only selected papers published in English were reviewed. The final reference list was generated on the basis of originality and relevance to the broad scope of this review.

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