Brain Research 907 (2001) 139–143 www.elsevier.com / locate / bres Short communication Gap junctions synchronize the firing of inhibitory interneurons in guinea pig hippocampus * Qizong Yang, Hillary B. Michelson Department of Physiology and Pharmacology, Box 29, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA Accepted 16 May 2001 Abstract The convulsant 4-aminopyridine (4AP) facilitates the synchronous firing of interneurons in the hippocampus, eliciting giant inhibitory postsynaptic potentials (IPSPs) in CA3 pyramidal cells. We used the gap junction blocker carbenoxolone to investigate the role of electrotonic coupling in both the initiation and the maintenance of 4AP-facilitated inhibitory circuit oscillations. Carbenoxolone abolished all synchronized IPSPs in CA3 cells elicited by 4AP in the presence of ionotropic glutamate receptor blockers. Carbenoxolone also blocked the isolated synchronized GABA IPSPs generated in CA3 cells by a subpopulation of interneurons. These data confirm that: (1) B the interneurons producing GABA responses in CA3 cells are electrotonically coupled, and (2) gap junctions among interneurons are B essential for initiating synchronized interneuron oscillatory firing in 4AP.  2001 Published by Elsevier Science B.V. Theme: Excitable membranes and synaptic transmission Topic: Postsynaptic mechanisms Keywords: Gap junctions; Electrotonic coupling; Interneuron; Inhibition We have been investigating the connectivity of the subset of GABAergic neurons continue to synchronously hippocampal inhibitory circuit, using the convulsant 4- fire, producing large amplitude GABA -mediated re- B aminopyridine (4AP) to synchronize GABAergic neuronal sponses in principal cells. These interneurons appear to be firing. In the presence of 4AP and ionotropic glutamate coupled by mechanisms other than traditional chemically- receptor blockers, hippocampal interneurons synchronous- mediated synapses [3,10]. In the present report, we use the ly burst fire, whereas all other primary cell populations in gap junction blocker carbenoxolone [16] to investigate the the hippocampus exhibit large amplitude inhibitory post- role of electrotonic coupling in the 4AP-facilitated oscillat- synaptic potentials (IPSPs). These synchronized IPSPs ory firing of the hippocampal inhibitory circuit. consist of a hyperpolarizing GABA potential, a depolariz- Transverse hippocampal slices, 400 mm thick, were A ing GABA -mediated potential and a GABA component prepared from guinea pigs (200–300 g) according to A B [9,10]. We have demonstrated that these synchronous standard procedures [10]. Slices were transferred to a IPSPs are generated by hippocampal interneurons that are gas–fluid interface recording chamber, and maintained at recurrently coupled via bicuculline-sensitive depolarizing 358C, at a pH of 7.4, exposed to a warmed, humidified GABA (dGABA) synapses. The dGABA synaptic re- atmosphere saturated with a 95% O –5% CO gas mix- A 2 2 sponse is essential for both eliciting this synchronized ture. The lower surfaces of the slices were in contact with triphasic IPSP in principal cells, and for determining the a perfusion solution of the following composition (mM): frequency at which the inhibitory circuit will oscillate. NaCl, 124; KCl, 5; CaCl , 2; MgCl , 1.6; NaHCO , 26; 2 2 3 Following pharmacologic GABA receptor blockade, a and D-glucose, 10. Control solutions also contained 4AP A (75 mM), ( RS )-3-(2-carboxypiperazin-4-yl)-propyl-1-phos- phonic acid (CPP, 20 mM, to block NMDA receptors), and *Corresponding author. Tel.: 11-718-270-1339; fax: 11-718-270- 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 mM, to 2241. E-mail address: hmichelson@netmail.hscbklyn.edu (H.B. Michelson). block AMPA receptors). Bicuculline methiodide (15 mM) 0006-8993 / 01 / $ – see front matter  2001 Published by Elsevier Science B.V. PII: S0006-8993(01)02582-3