NeuroanatomyGABAB receptors at glutamatergic synapses in the rat striatum
Section snippets
Animals and tissue preparation
The experiments were carried out on 12 male Sprague–Dawley rats (180–300 g; Charles River, Margate, Kent, UK). Environmental conditions for housing of the rats and all procedures that were performed were in accordance with the Animals (Scientific Procedures) Act of 1986 (UK). Every effort was made to use the minimum number of animals and to minimize suffering. They were deeply anesthetized with sodium pentobarbitone (200 mg/kg; i.p.; Sagatal; Rhône Mérieux, Tallaght, Dublin, Ireland) and perfused
Subcellular localization of GABAB1 and GABAB2 in the striatum
Immunolabeling for GABAB1 and GABAB2 was identified by the presence of the electron dense immunogold particles. Labeled structures generally contained multiple particles and it is on this labeling that our qualitative description of the distribution is based. However, structures were observed that possessed only one immunogold particle and, although we cannot be sure that they do not represent background labeling, the profile of structures labeled was similar to those labeled by multiple
Localization of GABAB receptor subunits in the striatum
Studies in knockout mice lacking either GABAB1 or GABAB2 have provided the most compelling evidence to date that GABAB receptors require both subunits in order to function normally in vivo (Prosser et al 2001, Schuler et al 2001, Gassmann et al 2004). In situ hybridization studies, however, have demonstrated that GABAB2 mRNA is at low or undetectable levels in rat striatum, whereas GABAB1 is more strongly expressed in both embryonic and adult striatum (Durkin et al 1999, Clark et al 2000,
Conclusions
The findings of the present study provide an anatomical substrate for the presynaptic effects of GABAB receptor stimulation at glutamatergic cortical and thalamic synapses in the striatum thus underpinning the close interactions between the major inhibitory and excitatory neurotransmitter systems in this nucleus. They also demonstrate that stimulation of synaptic and extrasynaptic GABAB receptors is likely to affect GABAergic transmission at both presynaptic and postsynaptic sites.
Acknowledgments
The work was funded by the Medical Research Council UK and the Research Grants Council of Hong Kong. C.J.L. is in receipt of a Medical Research Council studentship. We thank Caroline Francis, Ben Micklem, and Liz Norman for their expert technical assistance.
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Cited by (0)
- 1
Present address: Department of Physiology, Qingdao University, Qingdao 266021, China.
- 2
These authors contributed equally to this manuscript.