The coexistence of multiple receptors in a single nerve terminal provides evidence for pre-synaptic integration |
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Authors: | Ladera Carolina Godino María Del Carmen Martín Ricardo Luján Rafael Shigemoto Ryuichi Ciruela Francisco Torres Magdalena Sánchez-Prieto José |
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Affiliation: | Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain; Centro Regional de Investigaciones Biomédicas, Facultad de Medicina, Universidad Castilla –La Mancha, Albacete, Spain; Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan; Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain |
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Abstract: | Excitatory synaptic transmission is inhibited by G protein coupled receptors, including the adenosine A1, GABAB, and metabotropic glutamate receptor 7. These receptors are present in nerve terminals where they reduce the release of glutamate through activating signaling pathways negatively coupled to Ca2+ channels and adenylyl cyclase. However, it is not clear whether these receptors operate in distinct subpopulations of nerve terminals or if they are co-expressed in the same nerve terminals, despite the functional consequences that such distributions may have on synaptic transmission. Applying Ca2+ imaging and immunocytochemistry, we show that these three G protein coupled receptors coexist in a subpopulation of cerebrocortical nerve terminals. The three receptors share an intracellular signaling pathway through which their inhibitory responses are integrated and coactivation of these receptors produced an integrated response. Indeed, this response was highly variable, from a synergistic response at subthreshold agonist concentrations to an occluded response at high agonist concentrations. The presence of multiple receptors in a nerve terminal could be responsible for the physiological effects of neurotransmitter spillover from neighboring synapses or alternatively, the co-release of transmitters by the same nerve terminal. |
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Keywords: | adenosine A1 receptors cerebrocortical nerve terminals GABAB receptors glutamate release metabotropic glutamate receptor 7 pre-synaptic integration |
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