Hippocampal interneurons are excited via serotonin-gated ion channels.
Lori L. McMahon and Julie A. Kauer.
Department of Neurobiology, Duke University Medical Center, Durham, N.C.
27710, phone: (919) 681-6168, fax: (919) 684-4431, email:
juliek@neuro.duke.edu.
APStracts 4:165N, 1997.
ABSTRACT
Serotonergic neurons of the median raphe nucleus heavily innervate hippocampal
GABAergic interneurons located in stratum radiatum of area CA1, suggesting
that this strong subcortical projection may modulate interneuron excitability.
Using whole-cell patch clamp recording from interneurons in brain slices, we
tested the effects of serotonin (5-HT) on the physiological properties of
these interneurons. Serotonin produces a rapid inward current that persists
when synaptic transmission is blocked by tetrodotoxin and cobalt, and is
unaffected by ionotropic glutamate and GABA receptor antagonists. The 5-HT-
induced current was independent of G-protein activation. Pharmacological
evidence indicates that 5-HT directly excites these interneurons through
activation of 5-HT3 receptors.
At membrane potentials negative to -55 mV, the current-voltage (I-V)
relationship of the 5-HT current displays a region of negative slope
conductance. Therefore, the response of interneurons to serotonin strongly
depends on membrane potential, and increases greatly as cells are depolarized.
Removal of extracellular calcium, but not magnesium, increases the amplitude
of 5-HT-induced currents and removes the region of negative slope conductance,
thereby linearizing the I-V relationship.
The axons of 5-HT-responsive interneurons ramify widely within CA1; some of
these interneurons also project to and arborize extensively in the dentate
gyrus. The organization of these inhibitory connections strongly suggests that
these cells regulate excitability of both CA1 pyramidal cells and dentate
granule cells. As our results indicate that serotonin may mediate fast
excitatory synaptic transmission onto these interneurons, serotonergic inputs
can simultaneously modulate the output of both hippocampus and dentate gyrus.
Received 28 April 1997; accepted in final form 18 July 1997.
APS Manuscript Number J334-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 28 August 1997