Spontaneous recurrent network activity in organotypic rat hippocampal slices.
Organotypic hippocampal slices were prepared from postnatal day 4 rats and maintained in culture for >6 weeks. Cultured slices exhibited from 12 days in vitro spontaneous events which closely resembled giant depolarizing potentials (GDPs) recorded in neonatal hippocampal slices. GDP-like events occurred over the entire hippocampus with a delay of 30-60 ms between two adjacent regions as demonstrated by pair recordings from CA3-CA3, CA3-CA1 and interneurone-CA3 pyramidal cells. As in acute slices, spontaneous recurrent events were generated by the interplay of GABA and glutamate acting on AMPA receptors as they were reversibly blocked by bicuculline and 6,7-dinitroquinoxaline-2,3-dione but not by dl-2-amino-5-phosphonopentaoic acid. The equilibrium potentials for GABA measured in whole cell and gramicidin-perforated patch from interconnected interneurones-CA3 pyramidal cells were -70 and -56 mV, respectively. The resting membrane potential estimated from the reversal of N-methyl-D-aspartate-induced single-channel currents in cell-attach experiments was -75 mV. In spite of its depolarizing action, in the majority of cases GABA was still inhibitory as it blocked the firing of principal cells. The increased level of glutamatergic connectivity certainly contributed to network synchronization and to the development of interictal discharges after prolonged exposure to bicuculline. In spite of its inhibitory action, in a minority of cells GABA was still depolarizing and excitatory as it was able to bring principal cells to fire, suggesting that a certain degree of immaturity is still present in cultured slices. This was in line with the transient bicuculline-induced block of GDPs and with the isoguvacine-induced increase of GDP frequency.
Mohajerani
Majid H
MH
Neuroscience Program, International School for Advanced Studies, Via Beirut 2-4, 34014 Trieste, Italy.
Cherubini
Enrico
E
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid