Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum.
Activation of adenosine A2A receptors (A2AR) has been shown to antagonize the function of D2 dopaminergic regulation of striatal gamma-aminobutyric acid (GABA)-ergic output and, thus, locomotor activity. Adenosine A2A receptor immunoreactivity (A2A-LI) has been localized to rat striatum by light microscopy by using a previously characterized human A2AR monoclonal antibody. In this study, we evaluated the localization of A2A-LI and its colocalization with GABA immunoreactivity (GABA-LI) in dorsolateral rat striatum by immunoelectron microscopy to further characterize the potential mechanism of purinergic control of striatal output. Ultrastructural analysis demonstrated A2A-LI associated with the plasma membrane and cytoplasmic membranous structures of striatal neurons. A2A-LI was prevalent in dendrites and dendritic spines ( approximately 70% of total A2A-profiles counted) and less prevalent in axons and axon terminals (23%), soma (3%), and glia (3%). Cellular elements exhibiting both A2A-LI and GABA-LI comprised 23% of the total profiles counted; colabeling was most common in dendrites. A2A-LI was observed primarily at asymmetric synapses (n = 70) (both pre- and postsynaptically but predominantly in the postsynaptic element) and less frequently at symmetric synapses (n = 17). Of the 714 A2A-immunoreactive profiles examined, 37% were apposed to GABA-labeled profiles. The most common appositions were A2A-labeled dendrites apposed to GABA-immunoreactive dendrites (n = 132), axon terminals (n = 28), and somata (n = 22) and A2A-labeled axons apposed to GABA-labeled dendrites (n = 58), axon terminals (n = 14), and somata (n = 9). Our findings suggest that adenosine may play an important role in modulating excitatory input to striatal neurons and that A2AR may modulate GABAergic signaling at several cellular sites within the rat striatum.
Hettinger
B D
BD
Department of Cardiovascular Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Lee
A
A
Linden
J
J
Rosin
D L
DL
D000818:Animals; D000906:Antibodies; D001369:Axons / Q000737:chemistry / Q000648:ultrastructure; D003342:Corpus Striatum / Q000737:chemistry / Q000166:cytology*; D003712:Dendrites / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000033:anatomy & histology*; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000032:analysis* / Q000276:immunology; D013569:Synapses / Q000737:chemistry / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000032:analysis* / Q000276:immunology
D000906:Antibodies; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D005680:gamma-Aminobutyric Acid