Afferent Control of Nigral Dopaminergic Neurons The Role of GABAergic Inputs

In in vivo extracellular recordings from anesthetized adult rats, midbrain dopaminergic neurons fire spontaneously at low rates, averaging around 4 spikes/second (Bunney et al., 1973; Guyenet and Aghajanian, 1978; Deniau et al., 1978; Tepper et al., 1982). Under these conditions, the neurons exhibit 3 distinct patterns or modes of firing. The first is that of pacemaker-like firing, characterized by very regular interspike intervals (Wilson et al., 1977; Tepper et al., 1995). The second, and most common pattern of activity in vivo is a random, or occasional mode (Wilson et al., 1977), characterized by long post-firing inhibition which rises smoothly into a flat autocorrelation function indicating that the remaining interspike intervals are distributed randomly, best characterized by a Poisson distribution. The third, least common mode of firing, is burst firing, in which the neurons exhibit stereotyped bursts of 2-8 action potentials in which the first intraburst interspike interval is around 60 ms, followed by progressively increasing interspike intervals and progressively decreasing spike amplitudes (Grace and Bunney, 1984). The bursts are not usually rhythmic or continuous, and occur embedded in background random single-spike firing activity. Both in anesthetized and unanesthetized rats (Freeman et al., 1985), dopaminergic neurons often switch between different firing modes, and the three firing patterns are best thought of as a continuum, with the pacemakerlike firing on one end and burst firing on the other. However, in vitro, the burst pattern and the random pattern are not seen. Instead, virtually all dopaminergic neurons fire in the pacemaker mode (Grace, 1987; Kang and Kitai, 1993). The absence of the burst and random firing modes in vitro suggests very strongly that the different firing patterns of dopaminergic neurons are primarily controlled by afferent input. However, precisely which afferents are responsible for modulating the firing pattern of dopaminergic neurons has remained unclear.