The purpose of the proposal is to investigate the ability of dopamine, adenosine and 5-hydroxytryptamine to regulate GABA release from striatal nerve terminals in the globus pallidus and substantia nigra pars reticulate. Experiments will use patch pipettes in voltage clamp to record whole cell membrane currents in GP and SNR neurons in rat brain slices. Biopolar stimulation electrodes will be placed in the brain slice to evoke currents produced by release of GABA from afferent nerve terminals. The hypothesis is that dopamine acts at presynaptic D1 receptors to increase the release of GABA from nerve terminals in the SNR, whereas stimulation of adenosine A1 and 5-HT1B receptors reduce GABA release. In contrast, the potentially opposing influences of presynaptic dopamine D1 and adenosine A2A receptor-stimulation on GABA release from nerve terminals in the GP will be investigated. In addition, the hypothesis that the straitonigral pathway selectively releases GABA onto GABAB receptors on dopamine neurons in the sustantia nigra zona compacta will be tested.
| Martin, Melinda S; Dutt, Karoni; Papale, Ligia A et al. (2010) Altered function of the SCN1A voltage-gated sodium channel leads to gamma-aminobutyric acid-ergic (GABAergic) interneuron abnormalities. J Biol Chem 285:9823-34 |
| Shen, K Z; Johnson, S W (2001) Potentiation of GABA(A) receptor agonists by GABA uptake inhibitors in the rat ventral midbrain. Eur J Pharmacol 428:1-7 |
| Wu, Y N; Shen, K Z; Johnson, S W (1999) Presynaptic inhibition preferentially reduces in NMDA receptor-mediated component of transmission in rat midbrain dopamine neurons. Br J Pharmacol 127:1422-30 |
| Shen, K Z; Johnson, S W (1997) Presynaptic GABAB and adenosine A1 receptors regulate synaptic transmission to rat substantia nigra reticulata neurones. J Physiol 505 ( Pt 1):153-63 |
