Differential expression of GABA_BR1 and GABA_BR2 receptor immunoreactivity in neurochemically identified neurons of the rat neostriatum

Abstract

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the neostriatum. Functions of GABA are known to mediate GABA(A) and GABA(B) receptors. A functional GABA(B) receptor is known to compose of heteromeric subunits, namely the GABA(B)R1 and GABA(B)R2 subunits. Our previous report (Yung et al. [1999] Brain Res. 830:345-352) has demonstrated that all major subpopulations of striatal neurons express GABA(B)R1 immunoreactivity. The cellular localization of the second subunit of GABA(B) receptor protein, i.e., GABA(B)R2 immunoreactivity, in the rat neostriatum is not yet known. By using a new commercially available specific antibody against GABA(B)R2, immunofluorescence was performed to investigate the cellular expression of GABA(B)R2 in neurochemically identified subpopulations of neurons in the rat neostriatum. Immunoreactivity for GABA(B)R2 was primarily found in the neuropil of the rat neostriatum. Double labeling revealed that those perikarya that expressed immunoreactivity for parvalbumin, choline acetyltransferase, nitric oxide synthase, glutamate receptor two, N-methyl-D-aspartate receptor one, or GABA(A)alpha1 receptor, respectively, did not express GABA(B)R2 immunoreactivity. In addition, perikarya and most of the neuropilar elements in the neostriatum that expressed glutamic acid decarboxylase 67 immunoreactivity were found to be GABA(B)R2-negative. In contrast, immunoreactivity for GABA(B)R1 was found to be expressed by all of the above neuronal subpopulations. Moreover, a vast number of SV2-immunoreactive profiles and a number of tyrosine hydroxylase-immunoreactive profiles in the neuropil of the neostriatum were found to display GABA(B)R2 immunoreactivity. The present results indicate that there is a differential expression of GABA(B)R2 and GABA(B)R1 immunoreactivity in different subpopulations of striatal neurons that are identified by their specific neurochemical markers. Immunoreactivity for GABA(B)R2 is likely to localize in neuropilar elements of the neostriatum that may belong to non-GABAergic elements. These findings provide anatomical evidence of GABA(B)R2 receptor localization in the neostriatum that may have an important functional implication of the GABA(B)-mediated functions in neurons of the neostriatum.

Distribution and Function of GABABReceptors in Spider Peripheral Mechanosensilla

“…3D) originates most probably from the sensory axons and the glial cells. Similar difference in the R1 and R2 subunit immunoreactivity has been demonstrated in the rodent nervous system (Ng and Yung 2001;Yung et al 1999). The anti-GABA B R1 also produced some staining in the hypodermis membrane, but this staining was significantly sparser than that seen in the sensory neurons and may be unspecific staining.…”

“…Some of the anti-GABA B R1 staining may represent nonfunctional precursor molecules. Similar findings have been made with the same antibodies in human and rodent CNS and this has led to speculation that additional receptor subtypes may exist that could also dimerize with GABA B R1 to form functional receptors Ng and Yung 2001;Yung et al 1999). However, the significant amount of the anti-GABA B R1 staining did not coincide with the antisynapsin staining, suggesting that this receptor subtype in the spider peripheral tissue is expressed extrasynaptically as well as synaptically.…”

Redistribution of GABAB(1)Protein and Atypical GABABResponses in GABAB(2)-Deficient Mice

“…An increasing number of studies suggest that various cellular populations in the nervous system express GABA B(1) without GABA B(2) (Billinton et al, 2000;Calver et al, 2000;Clark et al, 2000;Ng and Yung, 2001;Burman et al, 2003;Kim et al, 2003;Kulik et al, 2003;Li et al, 2003;Straessle et al, 2003). Our results imply that neurons that naturally lack a GABA B(2) subunit nevertheless have the potential to express functional GABA B receptors.…”

“…However, no in vivo experiment addressed whether GABA B(1) can assemble functional GABA B receptors by itself or in association with a protein other than GABA B(2) . In support of a separate role, GABA B(1) exhibits a more widespread cellular distribution than does GABA B(2) Clark et al, 2000;Ng and Yung, 2001;Burman et al, 2003;Kim et al, 2003;Kulik et al, 2003;Li et al, 2003). Furthermore, at odds with a strict requirement of GABA B(2) for plasma membrane delivery, GABA B(1) was originally cloned by surface expression in mammalian cells (Kaupmann et al, 1997).…”

Differential Expression of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole-Propionate Glutamate Receptors in the Rat Striatum during Postnatal Development

“…Immunoreactivity for ChAT was employed as another specific neurochemical marker for striatal cholinergic interneurons, another major subpopulation of striatal interneurons [see 26]. In rats at PND7, no ChAT immunoreactivity was detected [21] (fig.…”