Know your brain: Locus coeruleus

Where is the locus coeruleus?

The locus coeruleus, which I'll refer to as the LC from here on out to avoid an inevitable misspelling, is a nucleus found in the pons. It is located near the floor of the fourth ventricle.

What is the locus coeruleus and what does it do?

The first descriptions of the LC date back to the late 1700s when French anatomist Félix Vicq d’Azyr detailed a blue-colored area of tissue in the pons. In the early 1800s, the term locus coeruleus, which means "blue spot" in Latin, was used to refer to that pigmented region. It wasn't until the second half of the twentieth century, however, that new techniques allowed scientists to learn that the blue coloring in the LC is caused by the production of a pigment formed by chemical reactions involving the neurotransmitter norepinephrine (also known as noradrenaline).

It is now known that the LC is the primary site of norepinephrine production in the brain. The nucleus sends norepinephrine throughout the cerebral cortex as well as to a variety of other structures including the amygdala, hippocampus, cerebellum, and spinal cord. In fact, the LC sends projections to virtually all brain regions except the basal ganglia, which seems to be lacking noradrenergic (i.e. noradrenaline/norepinephrine-related) input.

Because of the diversity of its projections and the diversity of the actions of norepinephrine as a neurotransmitter, the LC is involved in a long list of functions. It is perhaps most strongly linked, however, to arousal, vigilance, and attention. Neurons in the LC are less active during quiet wakefulness and their activity is even more diminished during sleep (indeed they are completely quiet during rapid eye movement, or REM, sleep), but they display increased activity in response to arousing stimuli. And optimal levels of norepinephrine in areas of the brain involved with attention, like the prefrontal cortex, have been found to be important to the facilitation of attention-related tasks.

Additionally, the LC and the norepinephrine it produces are thought to be integral to a number of higher cognitive functions ranging from motivation to working memory. It also seems to play a role in fine-tuning sensory signals to increase acuity across multiple sense modalities. It should be noted, however, that norepinephrine has wide-ranging actions throughout the brain and any attempt to briefly summarize its functions (or, by extension those of the LC) is an oversimplification.

Aging is associated with a significant loss of neurons in the LC, and a number of disorders---including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy---are linked to deficits in the number of LC neurons. In fact, in Alzheimer's disease the number of LC neurons lost exceeds the number of acetylcholine neurons lost in the nucleus basalis and in Parkinson's disease the number of LC neurons lost exceeds the number of dopamine neurons lost in the substantia nigra. This is notable because neuronal loss in the nucleus basalis and substantia nigra are considered hallmark signs of Alzheimer's disease and Parkinson's disease, respectively. Although the impact of LC loss in these diseases is not fully understood, it is thought to contribute significantly to the pathology of these conditions.

References:

Counts SE, Mufson EJ. Locus Coeruleus. JK Mai and G Paxinos (Eds.). 2012; Elsevier, New York.

Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009 Mar;10(3):211-23. doi: 10.1038/nrn2573.