Modulation of striatal neuronal activity by glutamate and GABA: iontophoresis in awake, unrestrained rats

To examine the effects of glutamate (GLU) and gamma-aminobutyric acid (GABA ) and their interactions in the striatum under behaviorally relevant condit ions, single-unit recording was combined with microiontophoresis in awake, unrestrained rats. Iontopheretically applied GLU (0-40 nA, 20 s) excited al l spontaneously active neurons in dorsal (caudate-putamen) and ventral (acc umbens, core) striatum; phasic GLU-induced excitations (mean threshold 19.7 nA) were dose-dependent, inversely correlated with rate of basal activity (excitation limit similar to 65 imp/s), and highly stable during repeated G LU applications. GLU also excited silent and sporadically active units, whi ch greatly outnumbered spontaneously active cells, and enhanced neuronal ex citations associated with movement. Both spontaneously active and GLU-stimu lated striatal neurons were highly sensitive to GABA (0-40 nA, 20 s); most showed short-latency inhibitions during GABA diffusion from the pipette (0 nA) and the response quickly progressed to complete silence with a small in crease in current. The GABA-induced inhibition was current-dependent, equal ly strong on spontaneously active and GLU-stimulated units, and independent of neuronal discharge rate, but less stable than the GLU-induced excitatio n during repeated drug applications. Prolonged GABA application (0-20 nA, 2 -4 min) reduced basal impulse activity, but was less effective in attenuati ng the neuronal excitations induced by GLU or associated with movement. Our data support the role of GLU afferents in the phasic activation of striata l neurons and suggest that the effects of GLU strongly depend on the level of ongoing neuronal activity. The ability of GABA to modulate both basal an d GLU-evoked activity suggests that GABA, released from efferent collateral s and interneurons, plays a critical role in regulating neuronal activity a nd responsiveness to phasic changes in excitatory input. (C) 1999 Elsevier Science B.V. All rights reserved.