Modular organization of the brainstem noradrenaline system coordinates opposing learning states

@article{Uematsu2017ModularOO,
  title={Modular organization of the brainstem noradrenaline system coordinates opposing learning states},
  author={Akira Uematsu and Bao Zhen. Tan and Edgar A Ycu and Jessica Sulkes Cuevas and Jenny Koivumaa and F{\'e}lix Junyent and Eric J. Kremer and Ilana B. Witten and Karl Deisseroth and Joshua P. Johansen},
  journal={Nature Neuroscience},
  year={2017},
  volume={20},
  pages={1602-1611}
}
Noradrenaline modulates global brain states and diverse behaviors through what is traditionally believed to be a homogeneous cell population in the brainstem locus coeruleus (LC). However, it is unclear how LC coordinates disparate behavioral functions. We report a modular LC organization in rats, endowed with distinct neural projection patterns and coding properties for flexible specification of opposing behavioral learning states. LC projection mapping revealed functionally distinct cell… 
Locus Coeruleus Norepinephrine in Learned Behavior: Anatomical Modularity and Spatiotemporal Integration in Targets
TLDR
New evidence suggests that the modular input-output organization of the LC could enable transient, task-specific modulation of distinct brain regions, and future work must further assess whether this spatial modularity coincides with functional differences in LC-NE subpopulations acting at specific times, and how such spatiotemporal specificity might influence learned behaviors.
Redefining Noradrenergic Neuromodulation of Behavior: Impacts of a Modular Locus Coeruleus Architecture
TLDR
The concept of theLC as a singular nucleus and the role of the LC in diverse theories of brain function must be reconsidered based on the evidence supporting a modular LC based on multiple levels of observation.
The Locus Coeruleus Is a Complex and Differentiated Neuromodulatory System
TLDR
Interactions between LC cell pairs under urethane anesthesia suggest a partly differentiated and target-specific noradrenergic signal and it is shown that spike waveform width was related to ensemble membership, propensity for synchronization, and interactions with cortex.
Ascending noradrenergic excitation from the locus coeruleus to the anterior cingulate cortex
TLDR
It is demonstrated that LC-NA projections enhance or facilitate brain responses to pain and itch by potentiating glutamatergic synaptic transmissions in the ACC.
Axonal projection‐specific differences in somatodendritic α2 autoreceptor function in locus coeruleus neurons
TLDR
A limited α2AR control of electrical activity for prefrontal‐projecting LC neurons indicative of functional heterogeneity in the LC‐noradrenergic system is identified.
The Role of the Locus Coeruleus in Cellular and Systems Memory Consolidation
TLDR
Tracking the connectivity strength within learning-related large-scale networks combined with monitoring neuromodulatory activity and behavioral assessment of memory appear irreplaceable methodology for examining interactions between cellular and systems mechanisms of memory consolidation, which are both dependent on neurmodulation.
The locus coeruleus is a complex and differentiated neuromodulatory system
TLDR
The findings suggest that the LC conveys a highly complex, differentiated, and potentially target-specific neuromodulatory signal.
A locus coeruleus to dentate gyrus noradrenergic circuit modulates aversive contextual processing
TLDR
It was found that effects required β-adrenergic-mediated modulation of hilar interneurons to ultimately promote aversive generalization, suggesting that disruption of noradrenaline tone may serve as an important avenue for treating stress-induced disorders.
A brainstem-central amygdala circuit underlies defensive responses to learned threats
TLDR
It is found that inhibition and activation of locus coeruleus (LC) neurons decreases and increases freezing to aversively conditioned cues, respectively, which support the hypothesis that LC projections to CeA are required for the expression of defensive responses elicited by conditioned threats.
Active control of arousal by a locus coeruleus GABAergic circuit
TLDR
A local population of GABAergic neurons (LC-GABA) is revealed capable of modulating LC-NA activity and arousal, demonstrating distinct modes by which an inhibitory LC circuit regulates the gain and tone of arousal in the brain.
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