Advanced approaches for selective investigation of neuronal function and circuitry: The future of developing novel therapeutic strategies in neuropharmacology?

Abstract

Recent advances in neuroscience techniques and methods ushered in a new era in the research of neuronal function with unprecedented selectivity and temporal resolution. One of the main characteristics of these technical advances is the ability to selectively target and/or modulate specific neuronal subpopulations and circuits in both healthy and diseased brains. Although initially designed as tools to help researchers better understand the mechanisms underlying neuronal activity and complex behaviors, these novel approaches may also accelerate the process of drug discovery in many areas of neuroscience, and some may even potentially serve as novel therapeutic strategies. The application of different electrophysiological techniques is still considered essential in studying ion channel function and pharmacology, as well as network-level changes in brain activity. The cutting-edge methods for investigation of brain function include opto-and chemogenetics in freely behaving animals; both approaches enable highly selective control of neuronal activity using either a light stimulation (optogenetics) or a chemical ligand (chemogenetics) in both loss-and gain-of-function experiments. In this review paper, we aim to summarize recent scientific evidence on the state-of-the-art and provide information on these advances, taking into account both academic and pharmaceutical industry points of view.