Noradrenergic Modulation of Cognition in Health and Disease

Abstract

Norepinephrine released by the locus coeruleus modulates cellular processes and synaptic transmission in the central nervous system through its actions at a number of pre- and postsynaptic receptors. This transmitter system facilitates sensory signal detection and promotes waking and arousal, processes which are necessary for navigating a complex and dynamic sensory environment. In addition to its effects on sensory processing and waking behavior, norepinephrine is now recognized as a contributor to various aspects of cognition, including attention, behavioral flexibility, working memory, and long-term mnemonic processes. Two areas of dense noradrenergic innervation, the prefrontal cortex and the hippocampus, are particularly important with regard to these functions. Due to its role in mediating normal cognitive function, it is reasonable to expect that noradrenergic transmission becomes dysfunctional in a number of neuropsychiatric and neurodegenerative diseases characterized by cognitive deficits. In this review, we summarize the unique role that norepinephrine plays in prefrontal cortical and hippocampal function and how its interaction with its various receptors contribute to cognitive behaviors. We further assess the changes that occur in the noradrenergic system in Alzheimer's disease, Parkinson's disease, attention-deficit/hyperactivity disorder, and schizophrenia and how these changes contribute to cognitive decline in these pathologies.

Genetics of resilience: Implications from genome‐wide association studies and candidate genes of the stress response system in posttraumatic stress disorder and depression

“…The catecholamine NE is released from its main production site—the LC in the pons—upon stress‐induced activation of the noradrenergic system and transported to its various projection sites, including amygdala, hippocampus, hypothalamus, and prefrontal cortex (Bandelow et al, ). β‐adrenergic receptors as well as α‐adrenergic receptors and the NE transporter are considered to be involved or affected in various psychiatric disorders and resilience (Borodovitsyna, Flamini, & Chandler, ; Krystal & Neumeister, ). So far, however, there are no conclusive results on genetic variants of the NE system related to resilience.…”

Tyrosinemia Type 1 and symptoms of ADHD: Biochemical mechanisms and implications for treatment and prognosis

“…ADHD‐symptoms may be related to decreased function of the catecholamine transmitters dopamine and noradrenaline in prefrontal cortex (Borodovitsyna, Flamini, & Chandler, ; Volkow et al, ). Biosynthesis of catecholamines relies partly on phenylalanine that is converted into tyrosine by the liver enzyme phenylalanine hydroxylase (PAH, EC 1.14.16.1).…”

ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines

“…The LC is involved in mood, reward, and motor ability (Borodovitsyna et al, 2017; Dickinson et al, 1988; Neophytou et al, 2001). As ErbB4 was mainly deleted from the LC-NE neurons in TH-Cre;Erbb4 loxP/loxP mice, we hypothesized that TH-Cre;Erbb4 loxP/loxP mice might exhibit LC-related behavioral abnormalities.…”