1. Differences in the cholinergic suppression of afferent and intrinsic fiber synaptic transmission were studied in the rat piriform cortex. Extracellular and intracellular recording techniques were applied in an in vitro transverse slice preparation. Afferent and intrinsic fiber systems were differentially stimulated with electrodes placed in layer Ia or layer Ib, respectively. Synaptic responses were monitored in the presence of cholinergic agonists and antagonists. 2. Afferent and intrinsic fiber synaptic potentials measured extracellularly showed large differences in sensitivity to micromolar concentrations of the cholinergic agonists carbachol or (±)-muscarine, or to acetylcholine combined with neostigmine. Intrinsic fiber synaptic responses in layer Ib were strongly reduced in the presence of cholinergic agonists, whereas afferent fiber synaptic responses in layer Ia were largely unaffected. At a concentration of 100 μM, all three agonists caused a >60% decrease in the height of the intrinsic fiber synaptic potential but <15% reduction in the afferent fiber synaptic potential. 3. Intracellular recordings confirmed that the cholinergic agonist carbachol selectively suppresses intrinsic fiber synaptic potentials but not afferent fiber synaptic potentials recorded from the same pyramidal cell. 4. Dose- response curves to carbachol were obtained for both fiber systems using extracellular recording of evoked field potentials. Carbachol suppressed intrinsic fiber synaptic potentials with a coefficient of dissociation (K(D)) estimated at 2.9 μM and an inhibitory concentration for 50% response estimated at 6.6 μM. 5. Carbachol produced a proportionately greater suppression of the first pulse than the second pulse of a pulse pair. This increase in the level of facilitation accompanying suppression suggests a presynaptic mechanism. Carbachol did not change the time course of intracellularly recorded synaptic potentials, suggesting that the suppression is not due to postsynaptic inhibition. 6. The cholinergic antagonists atropine, scopolamine, and pirenzepine had no direct effect on the synaptic potentials. However, after perfusion with these antagonists, subsequent perfusion with carbachol caused much less suppression of the intrinsic fiber synaptic potential, suggesting the suppression is due to a muscarinic cholinergic receptor of the MI subtype. 7. With perfusion of high concentrations of carbachol or acetylcholine, a population spike appeared in the layer Ia synaptic potential, suggesting greater excitability of pyramidal cells to afferent fiber stimulation. Population spikes did not appear with intrinsic fiber stimulation. Intracellular recording showed increased spiking response to current injection in the presence of carbachol. 8. The selective suppression of intrinsic fiber synaptic transmission during learning may enhance cortical associative memory performance, as shown in the companion paper.
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