Locus coeruleus

The locus coeruleus (caeruleal nucleus) regulates attention and is an important mediator of stress reactions.
It is activated by orexin and sends the noradrenaline it produces to a number of brain regions that are involved in stress systems. The locus coeruleus produces 95% of the noradrenaline in the brain and is therefore a key control element of the sympathetic nervous system.
In addition, the locus coeruleus controls the interactions between the serotonergic and noradrenergic systems.
Chronic activation of the locus coeruleus appears to reduce the stress response. Chemical deactivation of the locus coeruleus temporarily reduces the response of the HPA axis, but the response still returns after prolonged stress.

• 1. Behaviors regulated by locus coeruleus
• 2. Activation, efferents, afferents of the locus coeruleus
• 3. Co-transmitters and co-peptides of the locus coeruleus
• 4. Involvement of the locus coeruleus in diseases
• 5. Miscellaneous

1. Behaviors regulated by locus coeruleus¶

The locus coeruleus is involved in the control of various behaviors:¹

• Attention
  • sustained attention
  • Attention control
  • (Mental) orientation in the sense of directed attention
• Arousal
• Stress reaction²
• Memory
• Regulation of the sleep stages
• emotional mood
• Sexual behavior
• motor functions
  • in the striatum³

2. Activation, efferents, afferents of the locus coeruleus¶

The locus coeruleus is part of the formatio reticularis, is stimulated by orexin and produces noradrenaline.

Afferences (incoming signals) from:

• MPFC
  • Constant stimulating input according to the activity level
• Nucleus paragigantocellularis
  • Integrates autonomous stimuli and environmental stimuli
• Nucleus prepositus perihypoglossalis
  • Controls horizontal and vertical eye movements, eye tracking movements and gaze fixation
• Lateral hypothalamus
  • Produces orexin

Efferents (outgoing signals):
At least 6 different LC neuron groups send noradrenaline to different brain regions via at least 6 different pathways⁴

1. Olfactory bulb
2. Frontal cortex
3. visual cortex
4. Thalamus and midbrain
5. Cerebellum
6. Spinal cord

Efferences are also used:

• Amygdala
• Hippocampus
• Brain stem
• Motor cortex⁴
• Hypothalamus
  • Paraventricular nucleus
• Tectum (dorsal mesencephalon)
• Thalamus
• Ventral tegmentum
• Neocortex
• Inferior olive⁴
• Striatum⁴
• Caudate putamen⁴

It is unclear whether the LC cell groups are controlled jointly or individually by the incoming afferents, whether they control their outgoing efferents in a uniform or differentiated manner, whether different LC cell groups have different tasks and whether temporal differences in the firing signal differentiated meanings. There is increasing evidence that the LC does not act as a uniform structure and that the different C neuron groups have differentiated tasks.

3. Co-transmitters and co-peptides of the locus coeruleus¶

Co-transmitters in locus coeruleus cells include noradrenaline:⁴

• Dopamine
• Galanin
• Neuropeptide Y
• BDNF
• Cocaine and amphetamine regulated transcript (CART)

4. Involvement of the locus coeruleus in diseases¶

The locus coeruleus is involved in various disorders, such as

• ADHD⁴
• Parkinson’s disease⁴
• Down syndrome¹
• Alzheimer’s disease⁴
• PTSD⁴
• Anxiety disorders⁴
  • LC - Overactivity
• Depression⁴
• Drug effects and addiction¹
• Epilepsy⁴
• Cognitive dysfunction⁴

5. Miscellaneous¶

Chronic activation of the locus coeruleus appears to reduce the stress response.⁵

Chemical deactivation of the locus coeruleus acutely and briefly reduced the response of the HPA axis. However, after 4 weeks of chronic stress, the HPA axis response was fully restored despite deactivated locus coeruleus .⁶ This indicates that the locus coeruleus appears to primarily mediate acute stress responses.

Sleep deprivation can lead to the death of locus coeruleus neurons.⁷

LC neurons are functionally active from birth and change postnatally. Noradrenaline is required for the development and survival of dopaminergic cells in the midbrain. Early loss of neurons in the locus coeruleus is a hallmark of Parkinson’s and other neurodegenerative diseases. Noradrenaline afferents via BDNF appear to provide trophic support for vulnerable midbrain dopamine neurons. The locus coeruleus of newborn and young organisms is rich in BDNF, which is essential for the neuronal survival of midbrain dopamine neurons⁸

Newborns appear to exhibit increased sensitivity of the LC to somatosensory stimuli, which diversifies later in development, resulting in a reduced response to innocuous stimuli and a more sensitive response to noxious stimuli.⁹ The enhanced neonatal LC response may underlie some unique features of infant learning, such as attachment¹⁰
A high level of maternal care influences the density of various receptors in the locus coeruleus in the direction of increased stress resistance:¹¹

• Benzodiazepine receptor (also in amygdala)
• α2-adrenoreceptor
• CRH receptor.