title: Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment.
abstract: Locus ceruleus (LC) neuronal activity is correlated with the waking state, yet LC lesions produce only minor alterations in daily wakefulness. Here, we report that sustained elevations in neurobehavioral and EEG arousal in response to exposure to an environment with novel stimuli, including social interaction, are prevented by selective chemical lesions of the LC in rats. Similar results are seen when the anterior cingulate cortex (ACC), which receives especially dense LC innervation, is selectively denervated of LC input or is ablated by the cell-specific neurotoxin ibotenic acid. Anterograde tracing combined with tyrosine hydroxylase immunohistochemistry demonstrates ACC terminals in apposition with the distal dendrites of LC neurons. Our data implicate the ACC as both a source of input to the LC as well as one of its targets and suggests that the two structures engage in a dialog that may provide a critical neurobiological substrate for sustained attention.
authors.affiliation: Department of Neurology, Program in Neuroscience and Division of Sleep Medicine Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. hgompf@bidmc.harvard.edu
authors.forename: Heinrich S
authors.initials: HS
authors.lastname: Gompf
authors.forename: Christine
authors.initials: C
authors.lastname: Mathai
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Fuller
authors.forename: David A
authors.initials: DA
authors.lastname: Wood
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Pedersen
authors.forename: Clifford B
authors.initials: CB
authors.lastname: Saper
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology; D002452:Cell Count; D002540:Cerebral Cortex / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004569:Electroencephalography; D004576:Electromyography; D004777:Environment; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007051:Ibotenic Acid / Q000633:toxicity; D007150:Immunohistochemistry; D007398:Interpersonal Relations; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000502:physiology; D012895:Sleep, REM / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014851:Wakefulness / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D016760:Proto-Oncogene Proteins c-fos; D007051:Ibotenic Acid; D014446:Tyrosine 3-Monooxygenase