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The Journal of Neuroscience, December 15, 2001, 21(24):9917-9929
Control of Dorsal Raphe Serotonergic Neurons by the Medial Prefrontal Cortex: Involvement of Serotonin-1A, GABAA, and Glutamate Receptors
Pau Celada, M. Victoria Puig, Josep M. Casanovas, Gemma Guillazo, and Francesc Artigas Department of Neurochemistry, Institut d' Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (Institut d'Investigacions Biomèdiques August Pi i Sunyer), 08036 Barcelona, Spain
Anatomical evidence indicates that medial prefrontal cortex (mPFC) neurons project to the dorsal raphe nucleus (DR). In this study, we functionally characterized this descending pathway in rat brain. Projection neurons in the mPFC were identified by antidromic stimulation from the DR. Electrical stimulation of the mPFC mainly inhibited the activity of DR 5-HT neurons (55 of 66). Peristimulus time histograms showed a silence of 150 ± 9 msec poststimulus (latency, 36 ± 1 msec). The administration of WAY-100635 and picrotoxinin partly reversed this inhibition, indicating the involvement of 5-HT1A and GABAA receptors. In rats depleted of 5-HT with p-chlorophenylalanine, the electrical stimulation of mPFC mainly activated 5-HT neurons (31 of 40). The excitations (latency, 17 ± 1 msec) were antagonized by MK-801 and NBQX. Likewise, MK-801 prevented the rise in DR 5-HT release induced by electrical stimulation of mPFC. The application of 8-OH-DPAT in mPFC significantly inhibited the firing rate of DR 5-HT neurons and, in dual-probe microdialysis experiments, reduced the 5-HT output in mPFC and DR. Furthermore, the application of WAY-100635 in mPFC significantly antagonized the reduction of 5-HT release produced by systemic 8-OH-DPAT administration in both areas. These results indicate the existence of a complex regulation of DR 5-HT neurons by mPFC afferents. The stimulus-induced excitation of some 5-HT neurons by descending excitatory fibers releases 5-HT, which inhibits the same or other DR neurons by acting on 5-HT1A autoreceptors. Afferents from the mPFC also inhibit 5-HT neurons through the activation of GABAergic interneurons. Ascending serotonergic pathways may control the activity of this descending pathway by acting on postsynaptic 5-HT1A receptors.
Key words: 5-hydroxytryptamine; 5-HT1A receptors; 5-HT release; AMPA/KA receptors; dorsal raphe nucleus; GABA receptors; NMDA receptors; medial prefrontal cortex
Copyright © 2001 Society for Neuroscience 0270-6474/01/21249917-13$05.00/0
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