Cell class-specific modulation of attentional signals by acetylcholine in macaque frontal eye field

Abstract

Significance Attention improves perceptual abilities by modulating sensory processing. A key transmitter for attentional control is the neurotransmitter acetylcholine. We show that acetylcholine promotes attentional signals in frontal cortex by differentially activating 2 cholinergic receptor types in different cell groups. Acetylcholine promotes attentional control signals through muscarinic receptors in specific subclasses of broad spiking cells. Moreover, it promotes attentional control signals through muscarinic and nicotinic receptor activation in specific subclasses of narrow spiking cells. Thus, attentional control signals in the frontal eye field (FEF) are supported through nicotinic and muscarinic receptor activation in a highly cell type-specific manner. Attention is critical to high-level cognition, and attentional deficits are a hallmark of cognitive dysfunction. A key transmitter for attentional control is acetylcholine, but its cellular actions in attention-controlling areas remain poorly understood. Here we delineate how muscarinic and nicotinic receptors affect basic neuronal excitability and attentional control signals in different cell types in macaque frontal eye field. We found that broad spiking and narrow spiking cells both require muscarinic and nicotinic receptors for normal excitability, thereby affecting ongoing or stimulus-driven activity. Attentional control signals depended on muscarinic, not nicotinic receptors in broad spiking cells, while they depended on both muscarinic and nicotinic receptors in narrow spiking cells. Cluster analysis revealed that muscarinic and nicotinic effects on attentional control signals were highly selective even for different subclasses of narrow spiking cells and of broad spiking cells. These results demonstrate that cholinergic receptors are critical to establish attentional control signals in the frontal eye field in a cell type-specific manner.