Quantitative effects of some muscarinic agonists on evoked surface‐negative field potentials recorded from the guinea‐pig olfactory cortex slice

Abstract

1 The effects of muscarinic receptor agonists on the electrically-evoked surface-negative field potential (N-wave) were measured in the guinea-pig olfactory cortex slice maintained in vitro.2 Bath-superfusion of (±)-muscarine, acetylcholine (ACh), carbachol (CCh), or methacholine (MCh) (10-200pM) produced reversible, dose-dependent depressions of the N-wave (ACh and MCh effects were observed in the presence of 1OyM neostigmine). The order of potencies (based on agonist dose causing 50% field depression: IC5o) was: ACh > muscarine > CCh > MCh. All four agonists depressed the field potential by 100% at doses greater than 500PM.3 Pilocarpine and bethanechol were weak agonists and only produced measurable effects at high doses (1-2 mM). Neither agonist evoked a maximum response at doses up to 10 mM. 4 The muscarinic ganglion stimulant, McN-A-343 yielded inconsistent results, depressing the field potential in some slices, but having no effect in others. Pre-application of a conditioning dose (100 M) of McN-A-343 reduced subsequent responses to CCh, suggesting possible partial agonist properties. 5Oxotremorine (up to 100 yM) did not depress the field potential, but it reversibly antagonized the effects of CCh. 6 It is concluded that reproducible, quantifiable responses to muscarinic agonists can be evoked in the olfactory cortex slice. We suggest this preparation may be useful for conducting pharmacological studies of 'intact' central muscarinic receptors.

Enhanced cholinergic suppression of previously strengthened synapses enables the formation of self-organized representations in olfactory cortex

“…Acetylcholine causes similar physiological effects in most cortical structures, including direct depolarization of neurons Benardo & Prince, 1982;Madison & Nicoll, 1984) and enhancement of long-term potentiation (Blitzer, Gil, & Landau, 1990;Brocher, Artola, & Singer, 1992;Patil, Linster, Lubenov, & Hasselmo, 1998). Experimental data in a number of different regions also shows that acetylcholine strongly suppresses excitatory glutamatergic synaptic transmission via presynaptic inhibition at intrinsic, recurrent synapses in cortical structures (Dutar & Nicoll, 1988;Gil, Connors, & Amitai, 1997;Hasselmo, Schnell, & Barkai, 1995;Hounsgaard, 1978;Hsieh, Cruikshank, & Metherate, 2000;Linster, Wyble, & Hasselmo, 1999;Williams & Constanti, 1988). In contrast, acetylcholine usually causes less presynaptic inhibition at afferent fiber synapses (Gil et al, 1997;Hsieh et al, 2000;Linster et al, 1999).…”

A quantitative study of the effects of some muscarinic antagonists on the guinea‐pig olfactory cortex slice

“…The methods used for preparation and recording from guinea-pig olfactory cortex slices are described in detail in the accompanying paper (Williams & Constanti, 1988). Schild plots (Arunlakshana & potential records show the peak N-wave depression measured after a 2 min bath-application of CCh, and on the far right is the corresponding slow-speed chart record of peak N-wave amplitude (individual downward deflections cannot be distinguished).…”

“…In the present study, we have investigated quantitatively the actions of pirenzepine on this preparation, in an attempt to determine the receptor subtype responsible for generating this muscarinic response. We have also attempted to clarify the actions of oxotremorine, which appeared to antagonize the muscarinic responses (Williams & Constanti, 1988). Some of the data in this study have been reported in a preliminary form Williams & Constanti, 1986).…”

“…In the experiment shown in Figure 1, control responses were obtained to a 100/M dose of carbachol (CCh) that produced a -50% reduction of the field potential after a 2min application (see Williams & Constanti, 1988). When consistent responses had been obtained to this dose (Figure la), the slice was perfused with 100 nm pirenzepine for 1 h and a 100pM CCh dose reapplied (Figure lb) represent the control dose-response relation (usually points at 20-35% and 60-80% field depression).…”

“…In lower brain areas (pons) (where M2-receptors are predominantly found; Mash & Potter, 1986) it has been shown that pirenzepine has a low pA2 value (-6.2-6.6;Egan & North, 1985; regions, which have a high density of Ml-binding sites showing high affinity for pirenzepine (Hammer et al, 1980;Watson et al, 1983). In the previous paper (Williams & Constanti, 1988) we described the properties of a muscarinic 'response' that can be measured in the guinea-pig olfactory cortex slice; namely, the muscarinic depression of the evoked surface-negative field potential (N-wave). In the present study, we have investigated quantitatively the actions of pirenzepine on this preparation, in an attempt to determine the receptor subtype responsible for generating this muscarinic response.…”