Activation of muscarinic receptors during blockade of GABA(A)-mediated inhibition induces synchronous epileptiform activity in immature rat hippocampus
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peer reviewed
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Neuroscience
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We investigated the effects of the cholinergic agonist carbachol (25 mu M) on the synaptic potentials recorded extracellularly and intracellularly from the CA3 area of immature hippocampal slices of the rat (postnatal days 10-20). In control conditions, carbachol reduced the amplitude of evoked synaptic responses (n=8) and did not induce any spontaneous synchronous activity (n=12); the depressant effect of carbachol was mimicked by acetylcholine (100 mu M, in eserine 10 mu M, n=5) and was reversed by the muscarinic antagonist atropine (1 mu M, n=2). The GABA(A)-receptor antagonist bicuculline (10 mu M) enhanced the amplitude and duration of the evoked synaptic responses and induced infrequent (0.016-0.045 Hz) spontaneous synchronous discharges in 23/37 of the slices. Application of carbachol in the presence of bicuculline reduced the amplitude of the evoked synaptic responses (n=21) and in addition induced synchronous discharges with rates of occurrence 0.075-0.225 Hz, in 64/68 slices. Both effects were mimicked by acetylcholine and eserine, and antagonized by atropine. The specific muscarinic antagonists pirenzepine (MI-type), tripitramine (M2-type), 4-diphenylacetoxy-N-methylpiperidine methiodide (M3-type) and tropicamide (M4-type) (all tested at 0.1-1 mu M) reversibly reduced the frequency of synchronous carbachol-induced discharges. In addition, these discharges were reversibly blocked by high Ca2+ perfusion medium (7 mM CaCl2, n=4) and by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M, n=7). Synchronous epileptiform discharges were recorded from both CAI and CA3 areas in intact slices (n=3), but only from CA3 following disruption of the CA1-CA3 synaptic connections (n=3). These experiments suggest that activation of muscarinic receptors during blockade of GABA,mediated potentials, may enhance synchronous epileptiform activity in immature (postnatal days 10-20) hippocampus, through activation of local excitatory circuits and that endogenous acetylcholine may be sufficient to play this role. (C) 1997 IBRO. Published by Elsevier Science Ltd.
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development, excitatory, cholinergic, spontaneous, ictal, interictal, guinea-pig hippocampus, excitatory synaptic transmission, pyramidal cells, 6-cyano-7-nitroquinoxaline-2,3-dione cnqx, induced epileptogenesis, cholinergic modulation, gabaergic intern
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<Go to ISI>://A1998YH16400011
http://ac.els-cdn.com/S0306452297003382/1-s2.0-S0306452297003382-main.pdf?_tid=a056c7ca-ad80-11e2-acca-00000aacb361&acdnat=1366878053_6c1e77d1d1ad8b1f195bc132a05db8a1
http://ac.els-cdn.com/S0306452297003382/1-s2.0-S0306452297003382-main.pdf?_tid=a056c7ca-ad80-11e2-acca-00000aacb361&acdnat=1366878053_6c1e77d1d1ad8b1f195bc132a05db8a1
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en
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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών