Activation of locus coeruleus by prefrontal cortex is mediated by excitatory amino acid inputs

Jodo, Eiichi; Aston‐Jones, Gary

doi:10.1016/s0006-8993(97)00703-8

Cited by 94 publications

(71 citation statements)

References 32 publications

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“…Thus, the potentiating effects of clonidine and KOR agonist together suggest that KOR-mediated inputs may act with a2-AR modulatory regions to regulate various excitatory inputs under differing behavioral states, as has been recently suggested (for review, see Flavin and Winder, 2013). In addition, there has been some evidence to suggest that a2-ARs regulate glutamatergic transmission from the mPFC inputs, which is thought to also influence NA activity in the LC (Arnsten and Goldman-Rakic, 1984;Jodo and Aston-Jones, 1997;Jodo et al, 1998). Here we report a pronounced and important role for KOR expression within the LC in addition to the KOR-dependent NA tone seen during reinstatement of cocaine place preference.…”

Section: Na -Kor Interactions In Kappa Opioid-mediated Cocaine Reinstmentioning

confidence: 79%

Locus Coeruleus Kappa-Opioid Receptors Modulate Reinstatement of Cocaine Place Preference Through a Noradrenergic Mechanism

Al‐Hasani

McCall

Foshage

et al. 2013

Neuropsychopharmacol

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Activation of kappa-opioid receptors (KORs) in monoamine circuits results in dysphoria-like behaviors and stress-induced reinstatement of drug seeking in both conditioned place preference (CPP) and self-administration models. Noradrenergic (NA) receptor systems have also been implicated in similar behaviors. Dynorphinergic projections terminate within the locus coeruleus (LC), a primary source of norepinephrine in the forebrain, suggesting a possible link between the NA and dynorphin/kappa opioid systems, yet the implications of these putative interactions have not been investigated. We isolated the necessity of KORs in the LC in kappa opioid agonist (U50,488)-induced reinstatement of cocaine CPP by blocking KORs in the LC with NorBNI (KOR antagonist). KOR-induced reinstatement was significantly attenuated in mice injected with NorBNI in the LC. To determine the sufficiency of KORs in the LC on U50,488-induced reinstatement of cocaine CPP, we virally re-expressed KORs in the LC of KOR knockout mice. We found that KORs expression in the LC alone was sufficient to partially rescue KOR-induced reinstatement. Next we assessed the role of NA signaling in KOR-induced reinstatement of cocaine CPP in the presence and absence of a a2-agonist (clonidine), b-adrenergic receptor antagonist (propranolol), and b 1 -and b 2 -antagonist (betaxolol and ICI-118,551 HCl). Both the blockade of postsynaptic b 1 -adrenergic receptors and the activation of presynaptic inhibitory adrenergic autoreceptors selectively potentiated the magnitude of KOR-induced reinstatement of cocaine CPP but not cocaine-primed CPP reinstatement. Finally, viral restoration of KORs in the LC together with b-adrenergic receptor blockade did not potentiate KOR-induced reinstatement to cocaine CPP, suggesting that adrenergic receptor interactions occur at KOR-expressing regions external to the LC. These results identify a previously unknown interaction between KORs and NA systems and suggest a NA regulation of KOR-dependent reinstatement of cocaine CPP.

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Section: Na -Kor Interactions In Kappa Opioid-mediated Cocaine Reinstmentioning

confidence: 79%

Locus Coeruleus Kappa-Opioid Receptors Modulate Reinstatement of Cocaine Place Preference Through a Noradrenergic Mechanism

Al‐Hasani

McCall

Foshage

et al. 2013

Neuropsychopharmacol

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“…This "top-down" theory raises the important question of whether the task-related neuronal activity of PFC neurons and the increases in frontal cortical NA release are causally interrelated. In monkeys, pyramidal neurons of the PFC send projections to LC NA neurons (Arnsten and Goldman-Rakic, 1984), and there is evidence in rats for a powerful excitatory input of PFC to LC cells (Jodo and Aston-Jones, 1997;Jodo et al, 1998). PFC neurons fire in response to cues that are being memorized and to stimuli that recall stored information and elicit the behavioral response (Fuster, 1973;Kubota et al, 1974;Niki, 1974).…”

Section: Discussionmentioning

confidence: 99%

Noradrenaline and Dopamine Elevations in the Rat Prefrontal Cortex in Spatial Working Memory

Rossetti¹,

Carboni²

2005

J. Neurosci.

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The role of prefrontal cortical dopamine (DA) in the modulation of working memory functions is well documented, but substantial evidence indicates that the locus ceruleus noradrenergic system also modulates working memory via actions within the prefrontal cortex (PFC). This study shows that PFC noradrenaline (NA) and DA dialysate levels phasically increase when rats perform correctly in a delayed alternation task in a T-maze, a test of spatial working memory. However, NA levels were markedly enhanced in animals trained to alternate compared with rats that acquired the spatial information about the location of food in the maze but were untrained to make a choice to obtain the reward. In contrast, PFC DA elevations occurred independently of whether the animal had acquired the trial-specific information for correct task execution. The contribution of anticipatory responses to catecholamine efflux was also evaluated by exposing rats to an environment signaling the presence of the reward in the successive alternation task. No conditioned NA efflux was observed in either group. In contrast, in both groups, DA efflux increased in the anticipatory phase of the test to the same levels of those reached during the task. These data provide the first direct evidence for a selective activation of PFC NA transmission during a spatial working memory task. We propose that, in the working memory task, DA is primarily associated with reward expectancy, whereas NA is involved in the active maintenance of the information about a goal and the rules to achieve it.

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“…Single-unit electrophysiology, cortical EEG recording, and microinjection via double-barreled pipette in anesthetized subjects were carried out as described previously (8,40,41). Rats received a 40-min exposure to 2% isoflurane before undergoing emergence testing in room air.…”

Section: Methodsmentioning

confidence: 99%

Designer receptor manipulations reveal a role of the locus coeruleus noradrenergic system in isoflurane general anesthesia

Vazey

Aston‐Jones

2014

Proc. Natl. Acad. Sci. U.S.A.

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251

228

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Mechanisms driving emergence from general anesthesia are not well understood. The noradrenergic brain nucleus locus coeruleus (LC) modulates arousal and may have effects on general anesthetic state. Using virally delivered designer receptors to specifically control LC norepinephrine (NE) neurons, we investigated the causal relationship between LC-NE activity and general anesthetic state under isoflurane. Selective activation of LC-NE neurons produced cortical electroencephalography (EEG) activation under continuous deep isoflurane anesthesia. Specifically, LC-NE activation reduced burst suppression in EEG and drove a rightward shift in peak EEG frequency with reduced δ EEG power and increased θ EEG power, measures of cortical arousal. LC-NE activation also accelerated behavioral emergence from deep isoflurane anesthesia; this was prevented with β or α1 noradrenergic antagonists. Moreover, these adrenoreceptor antagonists alone were sufficient to markedly potentiate anesthetic duration when delivered centrally or peripherally. Induction of anesthesia also was retarded by LC-NE activation. Our results demonstrate that the LC-NE system strongly modulates the anesthetic state, and that changes in LC-NE neurotransmission alone can affect the emergence from isoflurane general anesthesia. Taken together, these findings extend our understanding of mechanisms underlying general anesthesia and cortical arousal, and have significant implications for optimizing the clinical safety and management of general anesthesia. DREADD | RASSLA nesthetic agents are critical tools in modern medicine. General anesthesia is akin to a drug-induced transient coma-like state (1). Emergence from general anesthesia is currently a passive process in which the anesthetic agent is discontinued and the patient monitored for spontaneous recovery of physiological and behavioral signs of consciousness, which is a variable and unpredictable process in patient populations (1). There are no drugs available for actively reversing general anesthesia should procedural or safety considerations necessitate rapid emergence. Understanding the neural substrates involved in emergence can identify targets for reversing general anesthesia and reveal mechanisms involved in cortical arousal.Histaminergic, cholinergic, dopaminergic, and orexinergic/hypocertinergic pathways have been implicated in the emergence from general anesthesia (2-4). These pathways are important in arousal networks that regulate sleep and waking, among other actions. The locus coeruleus (LC)-norepinephrine (NE) brain system is a key arousal node (5); however, the function of LC-NE neurons in anesthetic emergence has been relatively understudied (6-8).The pontine nucleus LC projects NE fibers throughout the CNS and is the primary source of NE to the cerebral cortex, among other areas (9). The LC receives arousal influences via inputs from orexinergic and histaminergic neurons, as well as an indirect circadian input from suprachiasmatic nucleus via dorsomedial hypothalamus (5), and in turn regu...

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Activation of locus coeruleus by prefrontal cortex is mediated by excitatory amino acid inputs

Cited by 94 publications

References 32 publications

Locus Coeruleus Kappa-Opioid Receptors Modulate Reinstatement of Cocaine Place Preference Through a Noradrenergic Mechanism

Locus Coeruleus Kappa-Opioid Receptors Modulate Reinstatement of Cocaine Place Preference Through a Noradrenergic Mechanism

Noradrenaline and Dopamine Elevations in the Rat Prefrontal Cortex in Spatial Working Memory

Designer receptor manipulations reveal a role of the locus coeruleus noradrenergic system in isoflurane general anesthesia

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