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Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices
Journal article   Open access

Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices

Daniel J Chandler, Wen-Jun Gao and Barry D Waterhouse
Proceedings of the National Academy of Sciences - PNAS, v 111(18), pp 6816-6821
06 May 2014
DOI: https://doi.org/10.1073/pnas.1320827111
PMID: 24753596
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https://doi.org/10.1073/pnas.1320827111View
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Abstract

Efferent Pathways - anatomy & histology Motor Cortex - anatomy & histology Motor Cortex - physiology Efferent Pathways - physiology Norepinephrine - physiology RNA, Messenger - genetics Locus Coeruleus - anatomy & histology Rats Behavior, Animal - physiology Locus Coeruleus - physiology Male alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - metabolism RNA, Messenger - metabolism Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate - genetics Voltage-Gated Sodium Channel beta-3 Subunit - genetics Tyrosine 3-Monooxygenase - genetics Animals Vesicular Monoamine Transport Proteins - genetics Prefrontal Cortex - anatomy & histology Prefrontal Cortex - physiology Principal Component Analysis Receptors, AMPA - genetics
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.

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