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570313 
Journal Article 
GABAB receptors at glutamatergic synapses in the rat striatum 
Lacey, CJ; Boyes, J; Gerlach, O; Chen, L; Magill, PJ; Bolam, JP 
2005 
1 
Neuroscience
ISSN: 0306-4522
EISSN: 1873-7544 
136 
4 
1083-1095 
Although multiple effects of GABAB receptor activation on synaptic transmission in the striatum have been described, the precise locations of the receptors mediating these effects have not been determined. To address this issue, we carried out pre-embedding immunogold electron microscopy in the rat using antibodies against the GABAB receptor subunits, GABAB1 and GABAB2. In addition, to investigate the relationship between GABAB receptors and glutamatergic striatal afferents, we used antibodies against the vesicular glutamate transporters, vesicular glutamate transporter 1 and vesicular glutamate transporter 2, as markers for glutamatergic terminals. Immunolabeling for GABAB1 and GABAB2 was widely and similarly distributed in the striatum, with immunogold particles localized at both presynaptic and postsynaptic sites. The most commonly labeled structures were dendritic shafts and spines, as well as terminals forming asymmetric and symmetric synapses. In postsynaptic structures, the majority of labeling associated with the plasma membrane was localized at extrasynaptic sites, although immunogold particles were also found at the postsynaptic specialization of some symmetric, putative GABAergic synapses. Labeling in axon terminals was located within, or at the edge of, the presynaptic active zone, as well as at extrasynaptic sites. Double labeling for GABAB receptor subunits and vesicular glutamate transporters revealed that labeling for both GABAB1 and GABAB2 was localized on glutamatergic axon terminals that expressed either vesicular glutamate transporter 1 or vesicular glutamate transporter 2. The patterns of innervation of striatal neurons by the vesicular glutamate transporter 1- and vesicular glutamate transporter 2-positive terminals suggest that they are selective markers of corticostriatal and thalamostriatal afferents, respectively. These results thus provide evidence that presynaptic GABAB heteroreceptors are in a position to modulate the two major excitatory inputs to striatal spiny projection neurons arising in the cortex and thalamus. In addition, presynaptic GABAB autoreceptors are present on the terminals of spiny projection neurons and/or striatal GABAergic interneurons. Furthermore, the data indicate that GABA may also affect the excitability of striatal neurons via postsynaptic GABAB receptors. 
basal ganglia; vesicular glutamate transporters; VGLUT1; VGLUT2; corticostriatal; thalamostriatal