The Journal of Neurophysiology Vol. 79 No. 4 April 1998, pp. 2003-2012
Copyright ©1998 The American Physiological Society

Muscarinic Agonist-Induced Burst Firing in Immature Rat Olfactory Cortex Neurons In Vitro

M. Postlethwaite¹, A. Constanti¹, and V. Libri^{1, 2}

¹ Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, United Kingdom; and ² Department of Biology, University of Rome Tor Vergata, 00173 Rome, Italy

Postlethwaite, M., A. Constanti, and V. Libri. Muscarinic agonist-induced burst firing in immature rat olfactory cortex neurons in vitro. J. Neurophysiol. 79: 2003-2012, 1998. Age-related changes in pre-/postsynaptic muscarinic (mAChR) and metabotropic-glutamate (mGluR) responsiveness were studied in slices of olfactory cortex from both immature [postnatal day 16-22 (P16-P22)] and adult (P40) rats, using a conventional intracellular recording technique. In adult neurons, bath application of the mAChR agonist oxotremorine-M (OXO-M; 10 µM), or the selective mGluR agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (1S,3R-ACPD; 10 µM) evoked sustained membrane depolarizations, increases in input resistance, intense repetitive firing, and the appearance of a slow poststimulus afterdepolarizing potential (sADP). Excitatory postsynaptic potentials (EPSPs) evoked by local electrical stimulation of association fiber terminals were also depressed. In contrast, in neurons from immature slices, the 10 µM OXO-M-induced membrane depolarization was followed by the appearance of spontaneous rhythmic epileptiform activity, which was voltage independent and reversible on drug wash out. Epileptiform bursts were abolished or reduced by coapplication of tetrodotoxin (1 µM), atropine (1 µM), pirenzepine (100-200 nM), the N-methyl-D-aspartate (NMDA) receptor antagonist DL-amino-5-phosphonovaleric acid (DL-APV; 100 µM), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5-20 µM), the anesthetic-sedative barbiturate pentobarbitone (100 µM), or by raising the extracellular Mg²⁺ concentration, whereas a clear facilitatory effect was exhibited by the selective -aminobutyric acid-A (GABA_A) receptor blocker ()-bicuculline methiodide (10 µM). The epileptogenic effects induced by OXO-M were indistinguishable from those produced by 4-aminopyridine (4-AP; 100-200 µM), although these latter actions were unaffected by atropine. In slices from immature animals, electrical stimulation of layer III association fibers in the presence of 10 µM OXO-M was accompanied by a dramatic prolongation of evoked depolarizing postsynaptic potentials (PSPs), with the appearance of recurrent superimposed spike discharges. This effect was readily reversed on wash out of OXO-M. No comparable age-dependent differences were observed in the nature or time course of 1S,3R-ACPD-evoked pre- (or post)synaptic responses, even in immature cells where muscarinic epileptiform activity had previously been demonstrated. We suggest that the overall susceptibility toward muscarinic-induced epileptiform discharge in immature olfactory cortical neurons may depend on the functional integrity of presynaptic inhibitory mAChRs; additional contributing mechanisms were also considered.

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