Cholinergic interneurons suppress action potential initiation of medium spiny neurons in rat nucleus accumbens shell

Acetylcholine plays a crucial role in the regulation of neural functions, including dopamine release, synaptic activity, and intrinsic electrophysiological properties of the nucleus accumbens (NAc) shell. Although the effects of acetylcholine on the action potential properties of NAc medium spiny (MS) neurons have been reported, how intrinsic acetylcholine released from NAc cholinergic interneurons regulates the neural activity of MS neurons is still an open issue. To explore the cholinergic effects on the subthreshold responses and action potential properties of MS neurons in the NAc shell, we first tested the effects of carbachol, a non-selective cholinergic agonist, on MS neuronal activity. Then, we tested the effects of the activation of cholinergic interneurons on the electrophysiological properties of MS neurons via multiple whole-cell patch-clamp recordings. Bath application of carbachol induced resting membrane potential depolarization accompanied by an increase in the voltage response to negative current injection. These increases were blocked by the pre-application of pirenzepine, an M1 muscarinic receptor antagonist. In spite of the facilitative effect on voltage responses of negative current injection, carbachol diminished the characteristic slowly-depolarizing ramp potentials, which respond to positive current pulse injection. Thus, carbachol increased the rheobase and shifted the frequency-current curve toward the right. Repetitive spike firing of a cholinergic interneuron following positive current injection induced a similar increase in the rheobase, which delayed the action potential initiation in 38.9% MS neurons. In contrast to the bath application of carbachol, cholinergic interneuronal stimulation had little effect on the resting membrane potential in MS neurons. These results suggest that the acetylcholine released from a cholinergic interneuron is sufficient to suppress the repetitive spike firing of the adjacent MS neurons, although the depolarization of the resting membrane potential may require simultaneous activation of multiple cholinergic interneurons.