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This Article Full Text Full Text (PDF) All Versions of this Article: 574/3/699    most recent jphysiol.2006.104794v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Selina Mok, M. H. Articles by Kew, J. N. C. Search for Related Content PubMed PubMed Citation Articles by Selina Mok, M. H. Articles by Kew, J. N. C. Related Collections Neuroscience

¹ Schizophrenia and Bipolar Neurophysiology and Pharmacology, Psychiatry CEDD, GlaxoSmithKline, New Frontiers Science Park North, Harlow, Essex CM19 5AW, UK

The 7 subtype of the nicotinic acetylcholine receptor (7 nAChR) is prominently expressed in the hippocampus where it is thought to play a role in the regulation of cognitive function. In this study, we have investigated the effects of 5-hydroxyindole (5-HI), a positive modulator of the 7 nAChR, on GABAergic activity in hippocampal CA1 stratum radiatum interneurons in acute rat brain slices. Superfusion of 5-HI (100 µM) increased the mean frequency and amplitude of spontaneous IPSCs (sIPSCs). The potentiation was occluded by pretreatment of slices with: (1) a high concentration of the broad-spectrum agonist nicotine to desensitize the 7 receptor, (2) an 7 nAChR antagonist, and (3) tetrodotoxin to block action potential firing. These results indicate that facilitation by 5-HI was mediated by the 7 nAChR and required neuronal excitation. In contrast, 5-HI had no effect on sIPSCs recorded in hippocampal slices from younger animals, even though the expression of functional 7 nAChRs was confirmed by agonist application experiments. In these slices, 5-HI only enhanced sIPSCs after pretreatment with the acetylcholinesterase inhibitor Bw284c51. Taken together, our results suggest that 5-HI facilitates GABAergic transmission via excitation of the 7 nAChR, and that this effect requires the presence of the endogenous agonist ACh in the extracellular environment of the receptor.

(Received 5 January 2006; accepted after revision 5 May 2006; first published online 11 May 2006)
Corresponding author S. Mok: Psychiatry CEDD, GlaxoSmithKline, Harlow, Essex CM19 5AW, UK. Email: selina.m.mok{at}gsk.com

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