Cognitive, Behavioral, and Systems NeuroscienceResearch PaperPhasic responses in dorsal raphe serotonin neurons to noxious stimuli
Research highlights
▶ Clocklike DRN neurons are neurochemically heterogeneous. ▶ Clocklike serotonin neurons are excited by noxious footshocks. ▶ Bursting DRN neurons are uniformly serotinergic. ▶ Bursting serotonin neurons are inhibited by noxious footshocks.
Section snippets
Animals
Male Sprague–Dawley rats (220–400 g, Charles River) were used. They were housed collectively with ad libitum access to food and water, and maintained on a 12-h light/dark cycle. All experiments were conducted in accordance with the Animals (Scientific Procedures) Act 1986 (UK) and associated guidelines. Every effort was made to use the minimum number of animals and to minimize suffering.
Electrophysiological recordings and juxtacellular labeling
Anesthesia was induced with isoflurane (Isoflo, Abbott, Queenborough, Kent, UK), and maintained with urethane
Electrophysiological characteristics of neurochemically identified DRN neurons
We recorded extracellular activity from single neurons in the DRN and delivered noxious shocks (20 Hz, 5 mA, 4 s duration, 40 s interval) to the hind paws. Following each recording, we attempted to label the single neuron with neurobiotin using the juxtacellular technique (Pinault, 1996), and neurochemically identified post mortem with immunoflourescence for serotonin, tryptophan hydroxylase (the rate-limiting enzyme for serotonin synthesis) and tyrosine hydroxylase (the rate-limiting enzyme
Discussion
Our findings indicate that DRN serotonin neurons exhibit rapid, phasic responses to noxious stimuli. We show that clocklike serotonin neurons are excited by footshocks. These results are consistent with a central prediction of the hypothesis that they encode a prediction-error rule for aversive events (Daw et al., 2002). However, because our results were collected under anesthesia, in the absence of behavioral responses, relating these results to findings in freely-moving, awake animals is an
Acknowledgments
This work was supported by grant U120085816 from the U.K. Medical Research Council (MRC), a University Research Fellowship from The Royal Society and grant GAT2848 from The Gatsby Charitable Foundation to M.A.U. We thank Daniel I. Brierley for technical support. We also thank Frederic Brischoux, Subhojit Chakraborty, Peter Dayan, Quentin J. Huys, Rajeshwari Iyer, and Jessica Risner for comments on the manuscript.
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Present address: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.