The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems

Abstract

Mesostriatal projections, which arise from dopaminergic and non- dopaminergic neurons in the ventral tegmental area, substantia nigra, and retrorubral area, are compartmentally organized in the striatum. Anterograde axonal tract tracing with Phaseolus vulgaris- leucoagglutinin (PHA-L), combined with immunohistochemical localization of tyrosine hydroxylase (TH) and autoradiographic localization of mu- opiate receptor binding sites, shows that midbrain projections to the striatum are distributed to either the mu-opiate receptor-rich “patch” or the receptor-poor “matrix” striatal compartments. Three morphologically distinct mesostriatal afferent fiber types are labeled. The first type, type A, forms a plexus of relatively thin (0.1–0.4 micron), smooth fibers with small varicosities (0.3–0.6 micron). A second type, type B, is similar to the first in forming a plexus of fibers, but is slightly thicker (0.2–0.6 micron), with more frequent varicosities (0.4–1.0 micron) that give this fiber type a crinkled appearance. The third type, type C, constitutes a minority of striatal afferents and is characterized by its large caliber (0.4–0.7 micron) with large bulbous varicosities (1.2–2.0 micron). Projections of the ventral tegmental area (A10 cell group) are primarily dopaminergic type A fibers directed to the matrix of the ventromedial striatum, including the nucleus accumbens. The retrorubral area (A8 cell group) also provides predominantly dopaminergic type A fibers to the striatal matrix, but these are distributed dorsally. The substantia nigra contains a mixed population of neurons that project to the striatum. Some, located in the dorsal tier of the pars compacta (dorsal A9 cell group), provide dopaminergic type A fibers to the striatal matrix. Others, in the ventral tier of the pars compacta (ventral A9 cell group) and in the ventral tier of the pars reticulata (displaced A9 cells), provide dopaminergic type B fibers to the striatal patches. An additional set of substantia nigra neurons that are non-dopaminergic is the source of type C fibers to the striatal matrix. Thus, distinct dorsal and ventral sets of midbrain dopaminergic neurons project, respectively, to striatal matrix and patches, and there is a non- dopaminergic mesostriatal projection to the matrix.

Nicotinic receptors as CNS targets for Parkinson's disease

“…The α6α4β2β3 subtype may thus provide a unique marker for dopamine nerve terminals that are particularly sensitive to nigrostriatal degeneration. This possibility is consistent with previous work indicating that dopaminergic afferents from the nigra to the striatum are variably susceptible to nigrostriatal insults [114,115]. Studies to understand the molecular basis for this enhanced vulnerability have linked calbindin to nigrostriatal dopamine neuron survival [116][117][118] while neuromelanin has been negatively associated [119][120][121][122].…”

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

“…These dopaminergic cell groups have slightly different characteristics and projection patterns, innervating the striatum in a topographic manner (Figure 1). Dopaminergic neurons of the ventral tier of the SNpc projects to the patch compartment of the dorsolateral striatum (mainly putamen), through the nigrostriatal pathway (3,31), and is involved in in motor control (42). The dorsal part of the SNpc projects to the matrix of the ventromedial striatum (mainly caudate nucleus) through the mesocortical pathway and is associated with cognition, whereas the VTA projects to the matrix of the ventral striatum (nucleus accumbens) and is involved in reward (43,44).…”

“…Clustered dopaminergic neurons of the dorsal tier of the SNpr mainly target the striatal patch compartment. Moreover, the matrix-directed dopaminergic neurons express calbindin immunoreactivity, whereas dopaminergic neurons projecting to the patches do not (3). The remaining 10% of dopaminergic cells are located in the hypothalamus (A11-A15) (35) and the olfactory bulb (A16), involved in autonomic and endocrine functions, and olfaction, respectively (45).…”

“…It has been shown that the sensorimotor striatum located in the dorso-lateral striatum receives input both from the ventral tier of the SNpc and the scarce population of dopaminergic neurons in the SNpr (3,426,427) (Figure 1). This striatal region corresponds to our site of injection and may thus induce cell death in these neurons through DAT and/or AQP9, potentially reflecting a PD-specific pattern.…”

Pallidal control of substantia nigra dopaminergic neuron firing pattern and its relation to extracellular neostriatal dopamine levels

“…Both pars reticulata GABAergic projection neurons as well as pars compacta dopaminergic neurons receive innervation from striatonigral neurons. The two cell populations are unlikely to receive the same set of afferent information from the striatum, however, as the major input to the GABAergic neurons comes from the striatal matrix compartment whereas that to the dopaminergic neurons, at least to their somata, arises from the patch compartment (Gerfen, 1985;Gerfen et al, 1987).…”