On the synchronous activity induced by 4-aminopyridine in the CA3 subfield of juvenile rat hippocampus.
1. Extracellular field potential and intracellular recordings were made in the CA3 subfield of hippocampal slices obtained from 10- to 24-day-old rats during perfusion with artificial cerebrospinal fluid (ACSF) containing the convulsant 4-aminopyridine (4-AP, 50 microM). 2. Three types of spontaneous, synchronous activity were recorded in the presence of 4-AP by employing extracellular microelectrodes positioned in the CA3 stratum (s.) radiatum: first, inter-ictal-like discharges that lasted 0.2-1.2 s and had an occurrence rate of 0.3-1.3 Hz; second, ictal-like events (duration: 3-40 s) that occurred at 4-38 x 10(-3) Hz; and third, large-amplitude (up to 8 mV) negative-going potentials that preceded the onset of the ictal-like events and thus appeared to initiate them. 3. None of these synchronous activities was consistently modified by addition of antagonists of the N-methyl-D-aspartate (NMDA) receptor to the ACSF. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-10 microM) reversibly blocked interictal- and ictallike discharges. The only synchronous, spontaneous activity recorded in this type of medium consisted of the negative-going potentials that were abolished by the GABAA receptor antagonists bicuculline methiodide (5-20 microM) or picrotoxin (50 microM). Hence they were mediated through the activation of the GABAA receptor. 4. Profile analysis of the 4-AP-induced synchronous activity revealed that the gamma-aminobutyric acid (GABA)-mediated field potential had maximal negative amplitude in s. lacunosum-moleculare, attained equipotentiality at the border between s. radiatum and s. pyramidale, and became positive-going in s. oriens. These findings indicated that the GABA-mediated field potential presumably represented a depolarization occurring in the dendrites of CA3 pyramidal cells. 5. This conclusion was supported by intracellular analysis of the 4-AP-induced activity. The GABA-mediated potential was reflected by a depolarization of the membrane of CA3 pyramidal cells that triggered a few variable-amplitude, fractionated spikes or fast action potentials. By contrast, the ictal-like discharge was associated with a prolonged depolarization during which repetitive bursts of action potentials occurred. Short-lasting depolarizations with bursts of action potentials occurred during each interictal-like discharge. 6. The GABA-mediated potential recorded intracellularly in the presence of CNQX consisted of a prolonged depolarization (up to 12 s) that was still capable of triggering a few fast action potentials and/or fractionated spikes.(ABSTRACT TRUNCATED AT 400 WORDS)
Avoli
M
M
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Psarropoulou
C
C
Tancredi
V
V
Fueta
Y
Y
D015761:4-Aminopyridine / Q000494:pharmacology*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000367:Age Factors; D000818:Animals; D046508:Culture Techniques; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D011810:Quinoxalines; D018079:Receptors, GABA; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015761:4-Aminopyridine