Noradrenaline Regulation of Brain-Body Communication

Norepinephrine (NE) and its methylated form, epinephrine (Epi), are catecholamines that serve as both neurotransmitters and hormones, regulating a wide array of physiological functions. In the central nervous system (CNS), NE acts as a neurotransmitter, primarily released by the locus coeruleus (LC), to regulate vigilance states and optimize behavioral performance. It is also the primary neurotransmitter of the peripheral, sympathetic nervous system, responsible for tonic and reflexive changes to cardiovascular tone. Conversely, Epi operates primarily as a hormone released by the adrenal medulla, to regulate metabolic homeostasis and orchestrate the body's response to acute stress. While there is no evidence for direct connections between the central and peripheral adrenergic systems, various feedforward and feedback circuits enable them to collaborate and synchronize brain-body responses to stimuli. A notable example of this interaction is evident in the body's response to stress, where multiple adrenergic systems work in concert to elicit a fight-or-flight response to perceived danger. Reciprocal communication between the LC, other adrenergic systems in the brain, and the NE-driven sympathetic nervous system induces a state of heightened arousal, enhances the processing of sensory stimuli, and facilitates adaptive behavioral responses to stressors.In this chapter, we will explore adrenergic systems in the brain and body and share evidence for multiple channels of communication between them. We will trace the anatomical connections and physiological characteristics of NE-producing neurons in the brain and the peripheral nervous system. We will also describe adrenergic systems in the body, projections of the sympathetic postganglionic neurons, the vasal ganglia of the cranial nerve, and release of NE and Epi by the adrenal medulla into the bloodstream. Importantly, this chapter will elucidate the circuits and pathways of communication between NE in the central and peripheral nervous systems that regulate and synchronize cognitive processes and physiological responses. Finally, we will explore various neurological disorders, including chronic pain and Alzheimer's disease (AD), that show evidence for deficits in adrenergic systems and disruption of the communication between the brain and body.