Forebrain Cholinergic Systems and Cognition: New Insights Based on Rapid Detection of Choline Spikes Using Enzyme-Based Biosensors

Changes in acetylcholine (ACh) release in the forebrain represent a critical step in the activation of larger neuronal circuits mediating cognitive functions. Therefore, the development of methods which allow the assessment of ACh release at a high temporal and spatial resolution is of immense significance for behavioral and cognitive neuroscience research. In this chapter, we review evidence from in vivo studies utilizing choline-sensitive microelectrodes for the detection of rapid changes in extracellular choline levels as a spatially discrete and sensitive measure of cortical cholinergic transmission. We then summarize empirical data from our lab based on studies involving electrochemical recordings and real-time monitoring of ACh release in animals performing a cued-appetitive response task. Phasic cholinergic activation in the prefrontal cortex, demonstrated by second-based increases in cholinergic transmission during behaviorally significant cues triggering reward approach, suggests that cholinergic transients encode specific information pertaining to the detection of attention-demanding cues. These findings indicate that cortical cholinergic transmission mediates defined cognitive operations which are contrary to the traditional description of cortical ACh as a slowly acting neuromodulator influencing different arousal states.