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Article
Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices
Proceedings of the National Academy of Sciences of the United States of America (2014)
  • Daniel J. Chandler, Rowan University School of Osteopathic Medicine
  • Wen-Jun Gao, Drexel University
  • Barry D. Waterhouse, Rowan University School of Osteopathic Medicine
Abstract
The brainstem nucleus locus coeruleus (LC) is the primary source of norepinephrine (NE) to the mammalian neocortex. It is believed to operate as a homogeneous syncytium of transmitter-specific cells that regulate brain function and behavior via an extensive network of axonal projections and global transmitter-mediated modulatory influences on a diverse assembly of neural targets within the CNS. The data presented here challenge this longstanding notion and argue instead for segregated operation of the LC-NE system with respect to the functions of the circuits within its efferent domain. Anatomical, molecular, and electrophysiological approaches were used in conjunction with a rat model to show that LC cells innervating discrete cortical regions are biochemically and electrophysiologically distinct from one another so as to elicit greater release of norepinephrine in prefrontal versus motor cortex. These findings challenge the consensus view of LC as a relatively homogeneous modulator of forebrain activity and have important implications for understanding the impact of the system on the generation and maintenance of adaptive and maladaptive behaviors.
Keywords
  • Efferent Pathways,
  • Locus Coeruleus,
  • Motor Cortex,
  • Prefrontal Cortex,
  • Principal Component Analysis,
  • Messenger RNA,
  • Genetics,
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid,
  • NR1 NMDA receptor,
  • AMPA Receptors,
  • N-Methyl-D-Aspartate Receptors,
  • Slc18a2 protein,
  • Vesicular Monoamine Transport Proteins,
  • Voltage-Gated Sodium Channel beta-3 Subunit,
  • AMPA1 glutamate receptor ionotropic,
  • Tyrosine 3-Monooxygenase,
  • Norepinephrine
Publication Date
May 6, 2014
DOI
10.1073/pnas.1320827111
Citation Information
Daniel J. Chandler, Wen-Jun Gao and Barry D. Waterhouse. "Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices" Proceedings of the National Academy of Sciences of the United States of America Vol. 111 Iss. 18 (2014) p. 6816 - 6821 ISSN: 0027-8424
Available at: http://works.bepress.com/barry-waterhouse/3/