The locus coeruleus (LC) is the brainstem neuromodulatory nucleus responsible for most of the norepinephrine (NE) released in the brain. It has widespread projections throughout the neocortex, and has a critical role in regulating arousal and wakefulness. In addition, the LC-NE neuromodulatory system is currently thought to play a role in several cognitive functions such as attention, emotion, decision making and learning and memory.
See also:

Image and Location

Example from Astafiev et al., 2010, Science: neuromelanin image (N = 10):

Region of Interest image (ROI):

ROI Nifti image: LC nifti

The LC is difficult to identify on conventional MR images due to its small size (~ 1 cm in length in humans) and its location deep down in the brainstem, immediately adjacent to the fourth ventricle. On neuromelanin-sensitive images, it is identified as a spotty high signal intensity area in the upper pontine tegmentum. This is because the noradrenergic neurons in the LC contain abundant neuromelanin (like the neurons in the SNc).


Searches so far:

locus coeruleus [all] and fmri [all] locus coeruleus [all] and projections [all]

Most important references

=Reviews on anatomy, physiology and function of the locus coeruleus-norepinephrine system:=

  • Berridge CW, Waterhouse BD. 2003. The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42:33–84. link to paper
  • Sara SJ. 2009. The locus coeruleus and noradrenergic modulation of cognition. Nature reviews. Neuroscience, 10(3), 211-223. link to paper

=Classic paper about the effects of NE (and DA) on target neurons:=

  • Servan-Schreiber D, Printz H, Cohen JD. 1990. A network model of catecholamine effects: gain, signal to noise ratio, and behavior. Science 249: 892– 895. link to paper

=fMRI studies:=

  • Minzenberg, M. J., A. J. Watrous, et al. (2008). Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI. Science 322(5908): 1700-1702. link to paper
  • Astafiev, S. V., A. Z. Snyder, et al. (2010). Comment on “Modafinil shifts human locus coeruleus to low-tonic, high-phasic activity during functional MRI” and “Homeostatic sleep pressure and responses to sustained attention in the suprachiasmatic area”. Science 328(5976): 309. link tot paper
  • Keren, N. I., C. T. Lozar, et al. (2009). In vivo mapping of the human locus coeruleus. Neuroimage 47(4): 1261-1267. link to paper



=Major inputs:=

  • nucleus paragigantocellularis (PGi) in the ventrolateral rostral medulla
  • nucleus prepositus hypoglossi (PrH) in the dorsomedial rostral medulla.

=Other subcortical inputs:=

  • preoptic area dorsal to the supraoptic nucleus (part of the anterior hypothalamus)
  • areas of the posterior hypothalamus
  • Kolliker-Fuse nucleus (in rostral dorsal lateral pons, part of the pontine respiratory group)
  • mesencephalic reticular formation
  • VTA (Ornstein, et al., 1987, J Neural Transm)
  • limited inputs have also been reported from the caudal midbrain periaqueductal gray (PAG) and the ventromedial pericoerulear region

=Cortical inputs:=

  • In rats: none
  • In primates: orbitofrontal and anterior cingulate cortex (Rajkowski et al., 2000; Aston-Jones et al., 2002; Zhu et al., 2004; Aston-Jones & Cohen, 2005).


The LC innervates almost the entire forebrain, with the exception of the striatum. The LC has widespread projections throughout the neocortex, thalamus, midbrain, cerebellum and spinal cord (Aston-Jones, Foote, & Bloom, 1984; Berridge & Waterhouse, 2003).

=Comparative anatomy of the distribution of noradrenergic and dopaminergic projections in the rat brain= (From: Sara, 2009, Nat Rev Neurosci)

From: Sara, 2009, Nat Rev Neurosci
ACC, anterior cingulate cortex; AON, anterior olfactory nucleus; AP-VAB, ansa peduncularis–ventral amygdaloid bundle system; BS, brainstem nuclei; C, cingulum; CC, corpus callosum; CER, cerebellum; CTT, central tegmental tract; CTX, cortex; DB, dorsal bundle; DPS, dorsal periventricular system; F, fornix; FC, frontal cortex; FR, fasiculus retroflexus; H, hypothalamus; HF, hippocampal formation; ML, medial lemiscus; MT, mamillothalamic tract; OB, olfactory bulb; OT, olfactory tract; pc, pars compacta; PC, piriform cortex; PRC, perirhinal cortex; PT, pretectal area; RF, reticular formation; S, septum; SC, spinal cord; ST, stria terminalis; T, tectum; TH, thalamus)


Summary list

Noradrenergic innervation of the brain

The LC is responsible for most of the norepinephrine (NE) released in the brain. Effects of NE on target neurons depends on the receptor that is activated (Foote et al., 1983; reviewed in Berridge and Waterhouse, 2003): alpha1 adrenoceptor activation is often associated with excitation, and alpha2 adrenoceptor activation (the dominant type within LC itself) is associated with inhibition (Rogawski and Aghajanian, 1982; Williams et al., 1985). In addition, NE augments evoked responses (either excitatory or inhibitory), while decreasing spontaneous activity in many target neurons (Waterhouse et al., 1980, 1984; Waterhouse and Woodward, 1980). Thus, modulation of neuronal responses to other inputs is a prominent effect of NE on target neurons. This modulatory action of NE was captured in an early computational model as an increase in the gain of the activation function of neural network units (Servan-Schreiber, Printz, & Cohen, 1990).


For a long time, the LC-NE system has been associated with basic functions as arousal and environmental responsiveness. Tonic activity of LC-NE neurons strongly covaries with stages of the sleep-waking cycle: they fire most rapidly during waking, slowly during drowsiness and slow-wave/non-REM sleep, and become virtually silent during REM sleep (Hobson et al., 1975; Aston-Jones and Bloom, 1981a; Rasmussen et al., 1986; Rajkowski et al., 1998). In addition, LC neurons in rats and monkeys activate robustly following salient stimuli in many modalities that elicit behavioral responses (Foote et al., 1980; Aston-Jones and Bloom, 1981b; Grant et al., 1988).

Sensory processing

  • NE improves the signal to noise ratio in auditory, visual and somatosensory neurons (reviewed in Foote and Morrison, 1987, Annu Rev Neurosci)
  • Sensory gating: in some cases increasing extracellular NE can shift non-responsive neurons to a responsive mode
  • Modulation of visual cortical plasticity (Bear & Singer, 1986, Nature; Kirkwood et al., 1999, J of Neurosci)

Regulation of cognitive performance

Recent research has shown that the LC-NE system has specific functions in the control of behavior (e.g., Aston-Jones & Cohen, 2005; Sara, 2009). According to a recent theory, the adaptive gain theory (Aston-Jones & Cohen, 2005), the LC-NE system has a critical role in the optimization of behavioral performance — by facilitating responses to motivationally significant stimuli and regulating the tradeoff between exploitative and exploratory behaviors.
link to Aston-Jones & Cohen, 2005, Annu Rev Neurosci

Learning and Memory

Drug withdrawal

Opioids inhibit the firing of LC neurons, and opiate withdrawal induces hyperactivity of LC neurons.

Effects of stimulation

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Effects of lesions/inactivation

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Effects of microinjection

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Studies activating


Coordinates (x, y, z): [-4, -37, -25] , [6, -38, -26] average from Keren et al (2009) and Astafiev et al (2010)

Specific study coordinates (if not too many)

Study Description x y z
Keren 2009 neuromelanin signal -3.7 -37 -24
Keren 2009 neuromelanin signal -4.7 -37 -27
Keren 2009 neuromelanin signal 5.8 -37 -27
Astafiev 2010 neuromelanin signal -3.2 -38 -25
Astafiev 2010 neuromelanin signal 5.4 -38 -25
Last modified: 2017/09/27 22:54