Opposing effects of striatonigral feedback pathways on midbrain dopamine cell activity.

The existence of a striatonigral GABAergic pathway has been well established both anatomically and biochemically. During intracellular recording from identified DA neurons in vivo, stimulation of the striatum (100 microA, 50 microseconds pulses) elicits an inhibitory postsynaptic potential (IPSP) and a rebound depolarization. The IPSP is a short latency (1.8-2.2 ms) conductance increase to chloride, since: the reversal potential is near the chloride reversal potential reported for other cells (-68 mV); intracellular chloride injection progressively reverses the IPSP into a depolarization with a similar time course; and the response of DA cells to systemic injection of the chloride channel blocker, picrotoxin, also exhibits a similar reversal potential. In contrast, during extracellular recording, stimulation of the striatum at low levels of intensity (e.g. 20 microA at 10 Hz) increases the firing rate of DA cells. Stimulation of the striatum will, in addition, elicit IPSPs in a subclass of substantia nigra zona reticulata neurons at the same latency as the IPSPs triggered in DA cells. These IPSPs also reverse with intracellular chloride injection. However, their amplitude is larger and their duration longer than observed in DA cells, and there is no depolarizing rebound. The late component of the IPSP in the zona reticulata neurons corresponds temporally to the rebound depolarization seen in DA cells in response to striatal stimulation. In addition, when recorded extracellularly, striatal stimulation will inhibit the firing of this class of zona reticulata interneurons at the same stimulation parameters that will excite DA cells. These data suggest that striatal cells may send branched fast-conducting GABAergic projections to zona reticulata cells and DA cells. Furthermore, low levels of striatal stimulation can excite DA cells by preferentially inhibiting interneurons in the zona reticulata which are more sensitive to the inhibitory effects of GABA than are DA neurons.