title: Gap junctions between CA3 pyramidal cells contribute to network synchronization in neonatal hippocampus.
abstract: Direct electrical coupling between neurons through gap junctions is prominent during development, when synaptic connectivity is scarce, providing the additional intercellular connectivity. However, functional studies of gap junctions are hampered by the unspecificity of pharmacological tools available. Here we have investigated gap-junctional coupling between CA3 pyramidal cells in neonatal hippocampus and its contribution to early network activity. Four different gap junction inhibitors, including the general blocker carbenoxolone, decreased the frequency of network activity bursts in CA3 area of hippocampus of P3-6 rats, suggesting the involvement of electrical connections in the generation of spontaneous network activity. In CA3 pyramidal cells, spikelets evoked by local stimulation of stratum oriens, were inhibited by carbenoxolone, but not by inhibitors of glutamatergic and GABAergic synaptic transmission, signifying the presence of electrical connectivity through axo-axonic gap junctions. Carbenoxolone also decreased the success rate of firing antidromic action potentials in response to stimulation, and changed the pattern of spontaneous action potential firing of CA3 pyramidal cells. Altogether, these data suggest that electrical coupling of CA3 pyramidal cells contribute to the generation of the early network events in neonatal hippocampus by modulating their firing pattern and synchronization.
authors.affiliation: Neuroscience Center and Department of Biosciences, University of Helsinki, 00014, Helsinki, Finland. Electronic address: svetlana.lavrenova@gmail.com.
authors.forename: Svetlana M
authors.initials: SM
authors.lastname: Molchanova
authors.affiliation: Neuroscience Center and Department of Biosciences, University of Helsinki, 00014, Helsinki, Finland. Electronic address: johanna.huupponen@helsinki.fi.
authors.forename: Johanna
authors.initials: J
authors.lastname: Huupponen
authors.affiliation: Neuroscience Center and Department of Biosciences, University of Helsinki, 00014, Helsinki, Finland. Electronic address: sari.lauri@helsinki.fi.
authors.forename: Sari E
authors.initials: SE
authors.lastname: Lauri
authors.affiliation: Neuroscience Center and Department of Biosciences, University of Helsinki, 00014, Helsinki, Finland; Department of Veterinary Biosciences, University of Helsinki, 00014, Helsinki, Finland. Electronic address: tomi.taira@helsinki.fi.
authors.forename: Tomi
authors.initials: T
authors.lastname: Taira
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D002229:Carbenoxolone / Q000494:pharmacology; D005439:Flufenamic Acid / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D015767:Mefloquine / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D011803:Quinine / Q000494:pharmacology; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
chemical_list: D018377:Neurotransmitter Agents; D005439:Flufenamic Acid; D011803:Quinine; D002229:Carbenoxolone; D015767:Mefloquine
keywords: Action potential firing pattern; Carbenoxolone disodium salt (PubChem CID: 6419769); Development; Flufenamic acid (PubMed CID 3371); Gap junctions; Hippocampus; Mefloquine hydrochloride (PubChem CID 65329); Neuronal network activity; Quinine (PubChem CID 8549)