Electrophysiological and pharmacological characterization of serotonergic dorsal raphe neurons recorded extracellularly and intracellularly in rat brain slices

Extracellular and intracellular recordings were made from dorsal raphe (DR) neurons in frontal rat brain slices maintained in vitro. A population of neurons was found which displayed electrophysiological and pharmacological characteristics of serotonin-containing DR neurons recorded in vivo. Recorded extracellularly, these neurons displayed biphasic or triphasic action potentials of 1.5-3.0 ms duration, and discharged with a slow and steady rhythm. Recorded intracellularly these neurons displayed action potentials of about 1.8 ms duration, which were followed by large (10-20 mV) after hyperpolarizations which normally lasted 200-800 ms. These presumed serotonergic DR neurons were inhibited by LSD and serotonin. They were excited by norepinephrine, or the alpha-agonist phenylephrine, and these activations could be reduced or blocked by alpha-adrenoreceptor antagonists including the selective alpha 1-antagonist, prazosin. The major difference between the in vitro recordings and previous in vivo recordings from anesthetized animals was a reduction in the number of spontaneously firing DR neurons. This was probably due, at least in part, to a disfacilitation of serotonergic DR neurons in the slice caused by the functional removal of a tonic noradrenergic input.

[1]  D. van der Kooy,et al.  The nucleus raphe dorsalis of the rat and its projection upon the caudatoputamen. A combined cytoarchitectonic, immunohistochemical and retrograde transport study. , 1981, Journal de physiologie.

[2]  E. Kandel,et al.  Electrophysiological properties and functional interconnections of two symmetrical neurosecretory clusters (bag cells) in abdominal ganglion of Aplysia. , 1970, Journal of neurophysiology.

[3]  P. Adams,et al.  Control of calcium current in rat sympathetic neurons by norepinephrine , 1982, Brain Research.

[4]  G. Aghajanian,et al.  Suppression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists , 1980, Neuropharmacology.

[5]  B. Bunney,et al.  Inhibition of both noradrenergic and serotonergic neurons in brain by the α-adrenergic agonist clonidine , 1975, Brain Research.

[6]  G. Aghajanian,et al.  Reserpine suppression of dorsal raphe neuronal firing: mediation by adrenergic system. , 1978, European journal of pharmacology.

[7]  G. A. Howell,et al.  In vitro recording of raphe unit activity: evidence for endogenous rhythms in presumed serotonergic neurons. , 1982, Life sciences.

[8]  G. Aghajanian,et al.  L-Tryptophan as a selective histochemical marker for serotonergic neurons in single-cell recording studies. , 1974, Brain research.

[9]  K. Fuxe,et al.  EVIDENCE FOR THE EXISTENCE OF MONOAMINE-CONTAINING NEURONS IN THE CENTRAL NERVOUS SYSTEM. I. DEMONSTRATION OF MONOAMINES IN THE CELL BODIES OF BRAIN STEM NEURONS. , 1964, Acta physiologica Scandinavica. Supplementum.

[10]  J. Barker,et al.  Peptide regulation of neuronal membrane properties , 1976, Brain Research.

[11]  B. Jacobs,et al.  Recording of dorsal raphe unit activity in vitro , 1976, Neuroscience Letters.

[12]  H. Steinbusch,et al.  Distribution of serotonin-immunoreactivity in the central nervous system of the rat—Cell bodies and terminals , 1981, Neuroscience.

[13]  F. Weight,et al.  Micromethods in neuropharmacology: an approach to the study of anesthetics. , 1967, Anesthesiology.

[14]  H. Reuter,et al.  The regulation of the calcium conductance of cardiac muscle by adrenaline. , 1977, The Journal of physiology.

[15]  R. Llinás,et al.  Electrophysiological analysis of synaptic transmission , 1969 .

[16]  R. Tsien,et al.  Excitable Tissues: The Heart , 1978 .

[17]  A. Katz,et al.  Control of calcium transport in the myocardium by the cyclic AMP-Protein kinase system. , 1975, Advances in cyclic nucleotide research.

[18]  C J CLEMEDSON,et al.  DYNAMIC RESPONSE OF CHEST WALL AND LUNG INJURIES IN RABBITS EXPOSED TO AIR SHOCK WAVES OF SHORT DURATION. , 1964, Acta physiologica Scandinavica. Supplementum.

[19]  H. Haas,et al.  A simple perfusion chamber for the study of nervous tissue slices in vitro , 1979, Journal of Neuroscience Methods.

[20]  G. Aghajanian,et al.  Intracellular identification of central noradrenergic and serotonergic neurons by a new double labeling procedure , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  M. Trulson,et al.  Chloral hydrate anesthesia alters the responsiveness of dorsal raphe neurons to psychoactive drugs. , 1983, Life sciences.

[22]  B. Jacobs,et al.  Effects of adrenergic drugs on raphe unit activity in freely moving cats. , 1981, European journal of pharmacology.

[23]  G. Aghajanian,et al.  Suppression of serotogenic neuronal firing by α-adrenoceptor antagonists: Evidence against gaba mediation , 1980 .

[24]  J. Horn,et al.  Alpha‐drenergic inhibition of calcium‐dependent potentials in rat sympathetic neurones. , 1980, The Journal of physiology.

[25]  W. Foote,et al.  Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe , 1968, Science.

[26]  Rex Y. Wang,et al.  Antidromically identified serotonergic neurons in the rat midbrain raphe: evidence for collateral inhibition , 1977, Brain Research.

[27]  F. Bloom,et al.  Lysergic acid diethylamide and serotonin: direct actions on serotonin-containing neurons in rat brain. , 1972, Life sciences. Pt. 1: Physiology and pharmacology.

[28]  G. Aghajanian,et al.  Intracellular recordings from serotonergic dorsal raphe neurons: pacemaker potentials and the effects of LSD , 1982, Brain Research.

[29]  G. Aghajanian,et al.  Collateral inhibition of serotonergic neurones in the rat dorsal raphe nucleus: Pharmacological evidence , 1978, Neuropharmacology.

[30]  G. Aghajanian,et al.  Lysergic acid diethylamide and serotonin: a comparison of effects on serotonergic neurons and neurons receiving a serotonergic input. , 1974, The Journal of pharmacology and experimental therapeutics.

[31]  G. Aghajanian,et al.  Serotonergic and non-serotonergic neurons of the dorsal raphe: reciprocal changes in firing induced by peripheral nerve stimulation , 1978, Brain Research.

[32]  G. Aghajanian,et al.  Relative potencies of alpha-1 and alpha-2 antagonists in the locus ceruleus, dorsal raphe and dorsal lateral geniculate nuclei: an electrophysiological study. , 1982, The Journal of pharmacology and experimental therapeutics.

[33]  L. Hood,et al.  Purification and primary structure of two neuroactive peptides that cause bag cell afterdischarge and egg-laying in Aplysia. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[34]  G. Aghajanian,et al.  Noradrenergic innervation of serotonergic neurons in the dorsal raphe: Demonstration by electron microscopic autoradiography , 1981, Brain Research.