Elsevier

Neuroscience

Volume 98, Issue 2, June 2000, Pages 295-300
Neuroscience

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

https://doi.org/10.1016/S0306-4522(00)00060-9Get rights and content

Abstract

We have previously described a population of 5-hydroxytryptamine neurons which repetitively fires bursts of usually two (but occasionally three or four) action potentials, with a short (<20 ms) interspike interval within a regular low-frequency firing pattern. Here we used a paradigm of electrical stimulation comprising twin pulses (with 7- or 10-ms inter-pulse intervals) to mimic this burst firing pattern, and compared the effects of single- and twin-pulse electrical stimulations in models of pre- and postsynaptic 5-hydroxytryptamine function. Firstly, we measured the effect of direct electrical stimulation (2 Hz for 2 min) of rat brain slices on efflux of preloaded [3H]5-hydroxytryptamine. In this in vitro model, twin-pulse stimulation increased the efflux of tritium by about twice as much as did single-pulse stimulation. This effect was evident in the medial prefrontal cortex (area under 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 microdialysis to monitor changes in endogenous extracellular 5-hydroxytryptamine in rat medial prefrontal cortex in response to electrical stimulation (3 Hz for 10 min) of the dorsal raphe nucleus. In this model, twin-pulse stimulation of the dorsal raphe nucleus increased 5-hydroxytryptamine by approximately 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 vivo extracellular recording to follow the response of postsynaptic neurons in the rat medial prefrontal cortex to 5-hydroxytryptamine released by dorsal raphe stimulation. Electrical stimulation of the dorsal raphe nucleus (1 Hz) induced a clear-cut poststimulus inhibition in the majority of cortical neurons tested. In these experiments, the duration of poststimulus inhibition 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-hydroxytryptamine neurons, short bursts of action potentials will propagate along the axon to the nerve terminal and will enhance both the release of 5-hydroxytryptamine and its postsynaptic effect.

Section snippets

Animals

Male Sprague–Dawley rats [250–300 g; Harlan–Olac, Bicester, U.K. (microdialysis and electrophysiological experiments) or Charles River, Budapest, Hungary (brain slice experiments)] were housed in groups of up to six under conditions of controlled temperature and lighting, with food pellets and water freely available. All in vivo procedures were carried out in accordance with the U.K. Animals (Scientific Procedures) Act, 1986, and its associated guidelines.

Measurement of [3H]5-hydroxytryptamine efflux in vitro

Electrically evoked efflux of [3H]5-HT

Effect of single- and twin-pulse stimulation on efflux of [3H]5-hydroxytryptamine in vitro

Electrical stimulation (2 min, 2 Hz) of the superfused brain slices increased the efflux of tritium, and this effect lasted for three or four fractions. In the same slice, stimulations comprising twin pulses evoked a greater efflux of tritium than did stimulations comprising single pulses (Fig. 1). Thus, following twin-pulse stimulation the peak of tritium efflux was increased, with no consistent effect on the duration of the response. This effect was independent of the order in which the twin-

Discussion

Recent electrophysiological studies have established the existence of neurons in the rat DRN and MRN which discharge action potentials in short, high-frequency bursts within an otherwise slow and regular firing pattern.16., 18. Much evidence suggests that these neurons are a subpopulation of 5-HT neurons (see Introduction). In the present study, we used a stimulation pattern of twin pulses (7–10-ms interspike interval) within a regular 1–3 Hz firing pattern to mimic the burst firing pattern of

Acknowledgements

This work was supported by an MRC programme grant (G9102310) and the Hungarian Research Fund OTKA (T025060).

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§

Present address: Psychiatry Research Laboratory, The Medical School, Newcastle, U.K.

Present address: Pharmacia Corp., Kalamazoo, MI-49007, U.S.A.

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