On the Synchronous Activity-Induced by 4-Aminopyridine in the Ca3 Subfield of Juvenile Rat Hippocampus

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1993 (EN)
On the Synchronous Activity-Induced by 4-Aminopyridine in the Ca3 Subfield of Juvenile Rat Hippocampus (EN)

Avoli, M. (EN)

Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών (EL)
Avoli, M. (EN)

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 muM). 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, interictal-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 . 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 muM) reversibly blocked interictal- and ictal-like discharges. The only synchronous, spontaneous activity recorded in this type of medium consisted of the negative-going potentials that were abolished by the GABA, receptor antagonists bicuculline methiodide (5-20 muM) or picrotoxin (50 muM). Hence they were mediated through the activation of the GABA(A) 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. This depolarization lacked the initial hyperpolarization that often precedes a similar potential generated by adult (greater-than-or-equal-to 40-day-old) hippocampal cells perfused with ACSF containing 4-AP and CNQX. 7. Presumed glial cells recorded intracellularly in CA3 generated depolarizations that correlated in time with the three types of spontaneous field potentials induced by 4-AP. These depolarizations attained an initial peak (amplitude, 11-36 mV) within 200 ms from the onset of the GABA-mediated potential, grew further up to 20-48 mV during the initial phase of the ictal-like discharge, and returned toward baseline over several tens of seconds. Glial depolarizations were thought to reflect mainly increases in [K+]o. 8. After blockade of excitatory synaptic transmission, glial cells generated a prolonged depolarization during each GABA-mediated field potential. Segregation of some characteristics of these depolarizations according to age, revealed that their amplitude and duration were greater in the 10- to 14-day-old group than in the 18- to 23-day-old group. Moreover, values obtained from either juvenile group were significantly larger than those seen in adult rats. 9. It is concluded that both interictal- and ictal-like epileptiform discharges induced by 4-AP in the CA3 subfield of juvenile rat hippocampal slices are caused by an excitatory synaptic mechanism mediated through the activation of non-NMDA receptors. In addition, our findings demonstrate that as in the adult rat hippocampus, 4-AP discloses a synchronous potential that is mediated through GABA(A) receptors, presumably located on the dendrites of pyramidal cells. 10. Our study also indicates that in the juvenile hippocampus the GABA-mediated potential can synchronize neurons and thus initiate ictal-like epileptiform discharges. In the light of our glial recordings, we propose that this phenomenon is mediated through an augmentation of [K+]o that is caused by the activation of GABA(A) receptors located on the dendrites. Such an increase in [K+]o is more pronounced in the juvenile hippocampus because of a decreased ability to regulate [K+]o at this stage of brain maturation. (EN)

penicillin-induced epileptogenesis (EN)

Πανεπιστήμιο Ιωαννίνων (EL)
University of Ioannina (EN)

J Neurophysiol (EN)



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