Neurochemical and electrophysiological studies on the functional significance of burst firing in serotonergic neurons

We have previously described a population of 5-hydroxytryptamine neurons wh ich repetitively fires bursts of usually two (but occasionally three or fou r) action potentials, with a short (<20 ms) interspike interval within a re gular Low-frequency firing pattern. Here we used a paradigm of electrical s timulation comprising twin pulses (with 7- or 10-ms inter-pulse intervals) to mimic this burst Bring pattern, and compared the effects of single- and twin-pulse electrical stimulations in models of pre- and postsynaptic 5-hyd roxytryptamine function. Firstly, we measured the effect of direct electric al stimulation (2 Hz for 2 min) of rat brain slices on efflux of preloaded [H-3]5-hydroxytryptamine. In this in vitro model, twin-pulse stimulation in creased the efflux of tritium by about twice as much as did single pulse st imulation. This effect was evident in the medial prefrontal cortex (area un der the curve: 2.59+/-0.34 vs 1.28+/-0.22% relative fractional release), as well as in the caudate-putamen (3.93+/-0.65 vs 2.17+/-0.51%) and midbrain raphe nuclei (5.42+/-1.05 vs 2.51+/-0.75%). Secondly, we used in vivo micro dialysis to monitor changes in endogenous extracellular 5-hydroxytryptamine in rat medial prefrontal cortex in response to electrical stimulation (3 H z for 10 min) of the dorsal raphe nucleus. In this model, twin-pulse stimul ation of the dorsal raphe nucleus increased 5-hydroxytryptamine by approxim ately twice as much as did single-pulse stimulation at the same Frequency ( area under the curve: 50.4+/-9.0 vs 24.2+/-4.4 fmol). Finally, we used in v ivo extracellular recording to follow the response of postsynaptic neurons in the rat medial prefrontal cortex to 5-hydroxytryptamine released by dors al raphe stimulation. Electrical stimulation of the dorsal raphe nucleus (1 Hz) induced a clear-cut poststimulus inhibition in the majority of cortica l neurons tested. In these experiments, the duration of poststimulus inhibi tion following twin-pulse stimulation was markedly longer than that induced by single-pulse stimulation (200+/-21 vs 77+/-18.5 ms). Taken together, the present in vitro and in vivo data suggest that in 5-hyd roxytryptamine neurons, short bursts of action potentials will propagate al ong the axon to the nerve terminal and will enhance both the release of 5-h ydroxytryptamine and its postsynaptic effect. (C) 2000 IBRO, Published by E lsevier Science Ltd. All rights reserved.