title: Regulation of GABA release by nicotinic acetylcholine receptors in the neonatal rat hippocampus.
abstract: 1. The whole-cell configuration of the patch-clamp technique was used to study the modulation of giant depolarizing potentials (GDPs) by nicotinic acetylcholine receptors (nAChRs) in CA3 hippocampal neurons in slices from postnatal day (P) 2-6 rats. 2. Bath application of nicotine increased GDP frequency in a concentration-dependent manner. For example, nicotine (0.5-1 microM) enhanced GDP frequency from 0.05 +/- 0.04 to 0.17 +/- 0.04 Hz. This effect was prevented by the broad-spectrum nicotinic receptor antagonist dihydro-beta-erythtroidine (DHbetaE, 50 microM) and partially antagonized by methyllycaconitine (MLA, 50 nM) a competitive antagonist of alpha7 nAChRs. GDP frequency was also enhanced by AR-17779 (100 microM), a selective agonist of alpha7 nAChRs. 3. The GABA(A) receptor antagonist bicuculline (10 microM) and the non-NMDA glutamate receptor antagonist DNQX (20 microM) blocked GDPs and prevented the effects of nicotine on GDPs. In the presence of DNQX, nicotine increased GABA-mediated synaptic noise, indicating that this drug may have a direct effect on GABAergic interneurons. 4. Bath application of edrophonium (20 microM), a cholinesterase inhibitor, in the presence of atropine (1 microM), increased GDP frequency, indicating that nAChRs can be activated by ACh released from the septo-hippocampal fibres. This effect was prevented by DHbetaE (50 microM). 5. In the majority of neurons tested, MLA (50 nM) and DHbetaE (50 microM) reduced the frequency of GDPs with different efficacy: a reduction of 98 +/- 11 and 61 +/- 29 % was observed with DHbetaE and MLA, respectively. In a subset of cells (40 % in the case of MLA and 17 % in the case of DHbetaE) these drugs induced a twofold increase in GDP frequency. 6. It is suggested that, during development, nAChRs modulate the release of GABA, assessed as GDPs, through distinct nAChRs. The rise of intracellular calcium via nAChRs would further strengthen GABA-mediated oscillatory activity. This can be crucial for consolidation of synaptic contacts and for the fine-tuning of the developing hippocampus.
authors.affiliation: Neuroscience Program and Istituto Nazionale di Fisica della Materia Unit, International School for Advanced Studies (SISSA),Via Beirut 2-4, 34014 Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Maggi
authors.forename: E
authors.initials: E
authors.lastname: Sher
authors.forename: E
authors.initials: E
authors.lastname: Cherubini
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007306:Insecticides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C408128:AR-R 17779; D001952:Bridged-Ring Compounds; C579165:Chrna7 protein, rat; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007306:Insecticides; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D013141:Spiro Compounds; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D009538:Nicotine; D000109:Acetylcholine; D000157:Aconitine; D001640:Bicuculline