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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
Dr Richard McQuade
Dr Sarah Judge
Gartside SE, Cole AJ, Williams AP, McQuade R, Judge SJ
European Journal of Neuroscience
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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.
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