Abstract
The cholinergic system is thought to orchestrate task engagement. However, we lack a detailed understanding of how transient shifts in performance may be influenced by rapid changes in acetylcholine (ACh) levels. Neurotransmitter-specific fluorescent genetically encoded sensor recordings using fiber photometry provide a method for overcoming these limitations. This approach allows monitoring of variations in local neurotransmitter release and can provide important details about neuromodulation without the need to target reporter expression to particular cells of interest or demand single-cell precision for signal analysis. It has proven technically difficult to examine circuit function in non-human primates (NHP) using genetic methods because transgene expression is frequently low and transient. Here, we describe the use of GRAB-ACh3.0 to examine the effect of cholinergic modulation on signal detection in V1 of a rhesus macaque. We used fiber photometry to measure GRAB-ACh3.0 activity with simultaneous single-cell electrophysiology, pupillometry, and eye tracking while the animal was engaged in a smooth pursuit task. Our results indicate that global ACh fluorescence in V1 correlates with performance in the task supporting the notion that momentary lapses of attention occur during periods of low ACh. Both ACh and LFP in V1 present a power peak between the frequencies 2 and 4 Hz. Global ACh fluorescence in V1 correlates with the firing rate of local neurons. These results highlight the role of cholinergic signaling in moment-to-moment fluctuations in behavioral output as well as neuronal activity, reinforcing the potential of cholinergic compensation to improve performance. To our knowledge, this is the first evidence of rapid neurotransmitter changes correlating with moment-to-moment fluctuations in behavioral output in primates. These results have important implications for understanding the neurochemical underpinnings of sustained attention and goal-directed performance and define a pharmaceutically targetable substrate to manage conditions like attention deficit disorder.