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AMPA and NMDA receptor regulation of firing activity in 5-HT neurons of the dorsal and median raphe nuclei.
Eur J Neurosci. 2007 May; 25(10):3001-8.EJ

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.

Authors+Show Affiliations

Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK. sasha.gartside@ncl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17509083

Citation

Gartside, S E., et al. "AMPA and NMDA Receptor Regulation of Firing Activity in 5-HT Neurons of the Dorsal and Median Raphe Nuclei." The European Journal of Neuroscience, vol. 25, no. 10, 2007, pp. 3001-8.
Gartside SE, Cole AJ, Williams AP, et al. AMPA and NMDA receptor regulation of firing activity in 5-HT neurons of the dorsal and median raphe nuclei. Eur J Neurosci. 2007;25(10):3001-8.
Gartside, S. E., Cole, A. J., Williams, A. P., McQuade, R., & Judge, S. J. (2007). AMPA and NMDA receptor regulation of firing activity in 5-HT neurons of the dorsal and median raphe nuclei. The European Journal of Neuroscience, 25(10), 3001-8.
Gartside SE, et al. AMPA and NMDA Receptor Regulation of Firing Activity in 5-HT Neurons of the Dorsal and Median Raphe Nuclei. Eur J Neurosci. 2007;25(10):3001-8. PubMed PMID: 17509083.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AMPA and NMDA receptor regulation of firing activity in 5-HT neurons of the dorsal and median raphe nuclei. AU - Gartside,S E, AU - Cole,A J, AU - Williams,A P, AU - McQuade,R, AU - Judge,S J, Y1 - 2007/05/17/ PY - 2007/5/19/pubmed PY - 2007/8/19/medline PY - 2007/5/19/entrez SP - 3001 EP - 8 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 25 IS - 10 N2 - 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. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/17509083/AMPA_and_NMDA_receptor_regulation_of_firing_activity_in_5_HT_neurons_of_the_dorsal_and_median_raphe_nuclei_ L2 - https://doi.org/10.1111/j.1460-9568.2007.05577.x DB - PRIME DP - Unbound Medicine ER -