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AMPA and NMDA receptor regulation of firing activity in 5-HT neurons of the dorsal and median raphe nuclei

Lookup NU author(s): Dr Sasha Gartside, Dr Andrew Cole, Professor Richard McQuade, Dr Sarah Judge

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Abstract

The glutamatergic regulation of 5-hydroxytryptamine (5-HT) neuronal activity has not been extensively studied. Here, we used extracellular single unit recording in midbrain slices to examine glutamate receptor mediated effects on 5-HT neuronal activity in the dorsal raphe nucleus (DRN) and the median raphe nucleus (MRN). Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; 1 and 3 microm) concentration-dependently increased firing in 5-HT neurons in both the DRN and the MRN. The response to AMPA was blocked by the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3(1H-4H)-dione (DNQX; 10 microm) but not the N-methyl-d-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP-5; 50 microm). NMDA (10-100 microm) also increased 5-HT neuronal firing in a concentration-dependent manner in both the DRN and MRN; a response that was blocked by AP-5 (50 microm). In some DRN neurons the NMDA response was partially antagonized by DNQX (10 microm) suggesting that NMDA, as well as directly activating 5-HT neurons, evokes local release of glutamate, which indirectly activates AMPA receptors on 5-HT neurons. Responses of DRN 5-HT neurons to AMPA and NMDA were enhanced by the gamma-amino-butyric acid (GABA)(A) receptor antagonist, bicuculline (50 microm), suggesting that both AMPA and NMDA increase local release of GABA. Finally in the DRN the 5-HT(1A) receptor antagonist, WAY100635 (100 nm), failed to enhance the response of 5-HT neurons to AMPA and caused only a small increase in the excitatory response to NMDA suggesting a low degree of tonic activation of 5-HT(1A) autoreceptors even when 5-HT neuronal firing rate is high.

Publication metadata

Author(s): Gartside SE, Cole AJ, Williams AP, McQuade R, Judge SJ

Publication type: Article

Publication status: Published

Journal: European Journal of Neuroscience

Year: 2007

Volume: 25

Issue: 10

Pages: 3001-3008

Print publication date: 01/05/2007

Date deposited: 03/11/2009

ISSN (print): 0953-816X

ISSN (electronic): 1460-9568

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1460-9568.2007.05577.x

DOI: 10.1111/j.1460-9568.2007.05577.x

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