GABA(A) RECEPTOR-MEDIATED INHIBITION OF RAT SUBSTANTIA-NIGRA DOPAMINERGIC-NEURONS BY PARS RETICULATA PROJECTION NEURONS

Evidence from electrophysiological studies has suggested an inhibitory interaction between GABAergic neurons in substantia nigra pars reticu lata and dopaminergic neurons in pars compacta. However, that this inh ibitory interaction is due to a projection from pars reticulata to par s compacta has never been demonstrated directly, nor has the GABAergic neuron that mediates the interaction been identified either electroph ysiologically or anatomically. To more closely examine interactions be tween substantia nigra pars reticulata GABA neurons and dopaminergic n eurons, single unit extracellular recordings were obtained from antidr omically identified nigrostriatal neurons and their response to antidr omic activation of nigral GABAergic projection neurons observed, Stimu lation of superior colliculus or thalamus produced a short latency inh ibition of dopaminergic neurons, This inhibition was blocked by local application of bicuculline but not 2-hydroxysaclofen, Bicuculline caus ed most dopaminergic neurons to fire in a bursty mode, whereas saclofe n caused most dopaminergic neurons to fire in a pacemaker-like mode, T he thalamin-evoked inhibition was not affected by kainate lesions of t he globus pallidus, but these lesions produced effects on firing patte rn identical to those produced by saclofen, These data demonstrate a s hort latency inhibition of nigral dopaminergic neurons mediated by GAB A, receptors that arises from the axon collaterals of pars reticulata projection neurons, We propose a model in which the firing pattern of nigral dopaminergic neurons in vivo is modulated differentially by dis inhibition of GABA(A) inputs arising from pars reticulata projection n euron axon collaterals and disinhibition of pallidonigral GABAergic in puts mediated by GABA(B) receptors.