Interpreting Chemical Neurotransmission in Vivo: Techniques, Time Scales, and Theories

Monitoring neurotransmitter levels is a major research strategy for determining the functions of neuronal systems, specifically the ascending neuromodulator systems. In this Viewpoint, we consider the impact of different methods for recording extracellular neurotransmitter levels in vivo on theories concerning the signaling mode(s) and functions of these neuronal systems. As exemplified by evidence from experiments using different methods to measure acetylcholine (ACh) signaling, both neuromodulatory and deterministic functions have been attributed to cholinergic activity. Technical and experimental advances now allow determination of the validity of such dual-signaling theories.