TY - JOUR

T1 - Noradrenergic control of cortico-striato-thalamic and mesolimbic cross-structural synchrony

AU - Dzirasa, Kafui

AU - Phillips, H. Westley

AU - Sotnikova, Tatyana D.

AU - Salahpour, Ali

AU - Kumar, Sunil

AU - Gainetdinov, Raul R.

AU - Caron, Marc G.

AU - Nicolelis, Miguel A.L.

N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.

PY - 2010/5/5

Y1 - 2010/5/5

N2 - Although normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials and single-neuron activity across 10 interconnected brain areas (ventral striatum, frontal association cortex, hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute 12-fold increase in grooming. Notably, treatment with a norepinephrine precursors (L-3,4-dihydroxyphenylalanine at 100 mg/kg or L-threo-dihydroxyphenylserine at 5 mg/kg) or a selective serotonin reuptake inhibitor (fluoxetine at 20 mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE-depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striato-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.

AB - Although normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials and single-neuron activity across 10 interconnected brain areas (ventral striatum, frontal association cortex, hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute 12-fold increase in grooming. Notably, treatment with a norepinephrine precursors (L-3,4-dihydroxyphenylalanine at 100 mg/kg or L-threo-dihydroxyphenylserine at 5 mg/kg) or a selective serotonin reuptake inhibitor (fluoxetine at 20 mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE-depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striato-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.

UR - http://www.scopus.com/inward/record.url?scp=77951799100&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.0764-10.2010

DO - 10.1523/JNEUROSCI.0764-10.2010

M3 - Article

C2 - 20445065

VL - 30

SP - 6387

EP - 6397

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 18

ER -