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The Journal of Neuroscience, October 8, 2008, 28(41):10386-10398; doi:10.1523/JNEUROSCI.2387-08.2008

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Behavioral/Systems/Cognitive
GABAergic Afferents Activate Both GABAA and GABAB Receptors in Mouse Substantia Nigra Dopaminergic Neurons In Vivo

Elena Brazhnik, Fulva Shah, and James M. Tepper

Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102

Correspondence should be addressed to Dr. James M. Tepper, Center for Molecular and Behavioral Neuroscience, Rutgers University–Newark, 197 University Avenue, Newark, NJ 07102. Email: jtepper{at}andromeda.rutgers.edu

Most in vivo electrophysiological studies of substantia nigra have used rats. With the recent proliferation of the use of mice for in vitro neurophysiological studies because of the availability of various genetically modified strains to identify the roles of various channels and proteins in neuronal function, it is crucial to obtain data on in vivo responses in mice to verify that the in vitro results reflect functioning of systems comparable with those that have been well studied in rat.

Inhibitory responses of rat nigral dopaminergic neurons by stimulation of afferents from striatum, globus pallidus, or pars reticulata have been shown to be mediated predominantly or exclusively by GABAA receptors. This is puzzling given the substantial expression of GABAB receptors and the ubiquitous appearance of GABAB synaptic responses in rat dopaminergic neurons in vitro. In the present study, we studied electrically evoked GABAergic inhibition in nigral dopaminergic neurons in C57BL/6J mice. Stimulation of the three major GABAergic inputs elicited stronger and longer-lasting inhibitory responses than those seen in rats. The early inhibition was GABAA mediated, whereas the later component, absent in rats, was GABAB mediated and selectively enhanced by GABA uptake inhibition. Striatal-evoked inhibition exhibited a slower onset and a weaker initial component compared with inhibition from globus pallidus or substantia nigra pars reticulata. These results are discussed with respect to differences in the size and neuronal density of the rat and mouse brain and the different sites of synaptic contact of the synapses from the three GABAergic afferents.

Key words: substantia nigra; dopaminergic; inhibition; striatonigral; pallidonigral; pars reticulata

Received May 27, 2008; revised Aug. 15, 2008; accepted Aug. 22, 2008.

Correspondence should be addressed to Dr. James M. Tepper, Center for Molecular and Behavioral Neuroscience, Rutgers University–Newark, 197 University Avenue, Newark, NJ 07102. Email: jtepper{at}andromeda.rutgers.edu
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