Compartmentalization of excitatory amino acid receptors in human striatum.

Abstract

Division of the mammalian neostriatum into two intermingled compartments called striosomes and matrix has been established by analysis of enzyme activity, neuropeptide distribution, nucleic acid hybridization, and neurotransmitter receptor binding. Striosomes and matrix are distinct with respect to afferent and efferent connections, and these regions provide the potential for modulation and integration of information flow within basal ganglia circuitry. The primary neurotransmitters of corticostriatal afferents are excitatory amino acids, but to date no correlation of excitatory amino acid receptors and striatal compartments has been described. We examined binding to the three pharmacologically distinct ionotropic excitatory amino acid receptors, N-methyl-D-aspartate, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and kainate, in human striatum using in vitro receptor autoradiography and compared the binding to striosomes and matrix histochemically dermed by acetylcholinesterase activity. Our findings reveal increased binding to N-methyl-D-aspartate receptors and a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in matrix relative to striosomes and increased kainate receptor binding in striosomes relative to matrix. These results suggest that afferent input to the two striatal compartments may be mediated by pharmacoloically distinct excitatory amino acid receptor subtypes.The mammalian neostriatum, composed of the caudate nucleus and putamen, participates in the modulation ofneuronal activity associated with cognitive, affective, and performance aspects of motor function. Abundant corticostriatal afferents from frontal, limbic, and primary sensorimotor cortex subserve these distinct but interrelated functions. Striatal efferents projecting to globus pallidus (GP) and substantia nigra (SN) integrate and modulate motor activities via direct and indirect pallidal motor circuits that ultimately project back to cerebral cortex. Recent evidence suggests that the neostriatum is able to maintain segregated information flow due to compartmentalization in mammalian caudate and putamen (1-11). Distinct regions within caudate and putamen have been defined in several species with histochemical techniques, in situ hybridization, and neurotransmitter receptor binding studies in rat (1,(12)(13)(14)(15), cat (10, 14, 16-20), primate (12, 14, 19-22), and human (20,(23)(24)(25)(26). These compartments, termed striosomes and matrix, exhibit distinct afferent and efferent connections. In rat, cat, and primate, striosomes receive input primarily from prefrontal cortex, insular cortex, and amygdala, whereas the major projection to matrix is from association and sensorimotor cortex (2,27,28). Within the feline and rat neostriatum, interneurons may function to allow striosomal/matrix interactions (29-31).Separate striatal circuitry is preserved for efferent connections of striatum, with striosomal neurons projecting mainly to the substantia nigra pars compacta (SNc) and the majority of matrix neurons projec...

Kainate Receptors in the Striatum: Implications for Excitotoxicity in Huntington's Disease

“…Overall, the whole human striatum is quite enriched in AMPA receptor binding sites but a slightly higher density is found in the matrix compartment (Dure et al, 1992). Analysis of striatal AMPA binding sites in various pathological conditions revealed: (1) either no significant differences (Healy et al, 1998) or increases (Noga et al, 1997) in AMPA binding sites in schizophrenics, (2) significant reductions in AMPA receptor bindings in the putamen of girls with Rett syndrome (Blue et al, 1999) and (3) significant decreases of AMPA binding sites in the caudate nucleus of Huntington's patients (Dure et al, 1991).…”

“…The localization of AMPA receptors in the human striatum has been studied in normal and pathological conditions by means of autoradiographic ligand binding (Dure et al, 1991(Dure et al, , 1992Lee and Choi, 1992;Ball et al, 1994;Noga et al, 1997;Healy et al, 1998;Blue et al, 1999), in situ hybridization (Bernard et al, 1996;Tomiyama et al, 1997;Healy et al, 1998) and light microscopic immunohistochemistry (Meng et al, 1997;Cicchetti et al, 1999). Overall, the whole human striatum is quite enriched in AMPA receptor binding sites but a slightly higher density is found in the matrix compartment (Dure et al, 1992).…”

Kainate Receptors in the Striatum: Implications for Excitoxicity in Huntington's Disease

“…Overall, the whole human striatum is quite enriched in AMPA receptor binding sites but a slightly higher density is found in the matrix compartment (Dure et al, 1992). Analysis of striatal AMPA binding sites in various pathological conditions revealed: (1) either no significant differences (Healy et al, 1998) or increases (Noga et al, 1997) in AMPA binding sites in schizophrenics, (2) significant reductions in AMPA receptor bindings in the PUT of girls with Rett syndrome (Blue et al, 1999) and (3) significant decreases of AMPA binding sites in the CD of Huntington's patients (Dure et al, 1991).…”

“…Ligand binding studies show dense NMDA binding sites throughout the whole extent of the CD, PUT and Ace, with a tendency to be slightly higher in the matrix than the patch compartment (Dure et al, 1992;Lee and Choi, 1992). As discussed above for the AMPA receptors, NMDA binding is affected in various brain diseases (Dure et al, 1991;Ulas et al, 1994;Noga et al, 1997;Blue et al, 1999).…”

“…The localization of AMPA receptors in the human striatum has been studied in normal and pathological conditions by means of autoradiographic ligand binding (Dure et al, 1991(Dure et al, , 1992Lee and Choi, 1992;Ball et al, 1994;Noga et al, 1997;Healy et al, 1998;Blue et al, 1999), in situ hybridization (Bernard et al, 1996;Tomiyama et al, 1997;Healy et al, 1998) and light microscopic immunohistochemistry (Meng et al, 1997;Cicchetti et al, 1999). Overall, the whole human striatum is quite enriched in AMPA receptor binding sites but a slightly higher density is found in the matrix compartment (Dure et al, 1992).…”