Norepinephrine and inhibitory transmission: Regional diversity and mechanisms of modulation

Norepinephrine, a stress-related neuromodulator, is a key regulator of synaptic transmission and neuronal activity. While the impact of norepinephrine on excitatory transmission has been frequently discussed, how norepinephrine regulates inhibitory transmission remains poorly understood. Norepinephrine modulates inhibitory synaptic function and the firing property of inhibitory neurons. These norepinephrine effects on inhibitory transmission are complex and often region- and inhibitory neuron subtype-specific. Malfunctioning of the norepinephrine-induced modulation of inhibitory transmission could underlie various brain diseases, especially norepinephrine-related psychiatric and neurodegenerative disorders. In this review, we examine findings on the expression of norepinephrine receptors in inhibitory neurons and norepinephrine-induced modulation of inhibitory transmission across different regions of the central nervous system. Furthermore, we discuss the role of adrenergic receptors, norepinephrine concentrations, signaling and inhibitory neuron subtypes in norepinephrine-induced modulation of inhibitory transmission. Overall, this review highlights inhibitory transmission as a major target of norepinephrine for influencing circuit functions and shaping behavioral outcomes.