In situ imaging of monoamine localization and dynamics

Recent advances in sample preparation protocols and instrumentation allow current imaging mass spectrometry (IMS) to enable the visualization of small molecule tissue localization, including that of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine. Although monoamine-producing neurons, and their projections and synaptic connections, have been thoroughly characterized, in situ monoamine localization within these circuits remains unclear. Moreover, studying the fluctuations in local monoamine concentration in response to physiological stimuli, drug administration, and neurodegenerative disease progression is worthwhile, and can be achieved by analyzing the in situ concentration maps afforded by coupling IMS with on-tissue derivatization protocols. Recent reports have shown that monoamines localize within cell bodies and also translocate to distant nerve terminals, indicating active transport along axons and/or local synthesis at the terminals. Moreover, IMS can reveal regionally segregated monoamine fluctuations, such as rapid dopamine fluctuation within the nucleus accumbens (NAc) subregion during pain sensation. Furthermore, since exogenous drug pharmacokinetics can also be visualized by IMS, this technique could provide powerful methodologies enabling the simultaneous imaging of monoamines and drugs that selectively regulate monoamine signaling, such as serotonin reuptake inhibitors (SSRIs). Therefore, IMS could reveal where SSRIs administered over the long-term accumulate and how they affect local monoamine metabolism.