Applications of functional neurotransmitter release imaging with genetically encoded sensors in psychiatric research

Abstract

Psychiatric research encompasses diverse methodologies to understand the complex interplay between neurochemistry and behavior in mental health disorders. Despite significant advancements in pharmacological interventions, there remains a critical gap in understanding the precise functional changes underlying psychiatric conditions and the mechanisms of action of therapeutic agents. Genetically encoded sensors have emerged as powerful tools to address these challenges by enabling real-time monitoring of neurochemical dynamics in specific neuronal populations. This prospective explores the utility of neurotransmitter binding genetically encoded sensors in uncovering the nature of neuronal dysregulation underpinning mental illness, assessing the impact of pharmaceutical interventions, and facilitating the discovery of novel treatments.

Fig. 1. Currently available neurotransmitter binding sensors and preclinical research example.

a Representative list of currently available GPCR and PBP based neurotransmitter binding sensors. b Example of a genetically encoded sensor used to better understand neuronal pattern changes that occur during drug addiction. The dopamine-binding sensor dLight has been used to demonstrate how heroin use changes dopamine-driven reward circuits, increasing reward response upon entry to locations of drug abuse. Adapted from [10].