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Journal of Neuroscience, Vol 10, 720-733, Copyright © 1990 by Society for Neuroscience
Patterns of cell and fiber vulnerability in the mesostriatal system of the mutant mouse weaver. I. Gradients and compartments
AM Graybiel, K Ohta and S Roffler-Tarlov
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
In mice carrying the autosomal recessive gene weaver, there is a massive
postnatal loss of dopamine in the caudoputamen, the target of the
nigrostriatal system, with relative (though not complete) preservation of
dopamine in the ventral striatum, a target of the mesolimbic system. There
is concomitant death of catecholaminergic neurons in the substantia nigra,
with much less cell death in the limbic midbrain area. In the study
reported here, we have reexamined the mesostriatal system of weaver mice by
means of tyrosine hydroxylase (TH) immunohistochemistry in order to
determine the local architecture of the defect within the striatum and
substantia nigra. For the dorsal striatum, the most striking finding was
the appearance in the weaver caudoputamen of small pockets of especially
weak immunostaining within a larger dorsal zone of generally reduced
TH-positive neuropil. These pockets were identified as striosomes by
calbindin28k and met- enkephalin immunohistochemistry carried out on
adjacent sections. In dorsal, central, and caudal sectors of the
caudoputamen, there was also more generalized depletion of
TH-immunoreactive neuropil. In the mid- brains of the mutants, the patterns
of loss of TH-positive neurons appeared to correspond to these
distributions of reduced immunostaining in the striatum. In the substantia
nigra pars compacta, ventrally situated TH-positive neurons were especially
affected, suggesting preferential depletion of TH-positive neurons
projecting to striosomes. In addition, there was a central sector of nearly
complete loss of TH- positive neurons in the substantia nigra para compacta
and a marked depletion of TH-positive neurons in cell group A8 that,
together, may have accounted for the diminution of TH-positive innervation
of the striatal matrix. We conclude that the effects of the weaver gene
discriminate among mesostriatal subsystems not only according to the
regional affiliations of these subsystems within the dorsal and ventral
striatum, but also according to the preferential association of the
subsystems for the striosomal and matrical compartments of the
caudoputamen. The depletion of TH-positive innervation was not confined to
the dorsal striatum proper. The defect extended into the adjoining nucleus
accumbens, where it appeared to affect the lateral "core" division, and
included also a lateral part of the olfactory tubercle. Thus, as in the
dorsal striatum, the defect in the TH-positive innervation of the ventral
striatum closely follows the local architecture of this striatal region.
Neuronal loss in the ventral tegmental area was not evident on qualitative
analysis, but at the border between lateral cell group A 10 and medial cell
group A9 there was obvious loss of immunostained neurons.(ABSTRACT
TRUNCATED AT 400 WORDS)
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