Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

Samuels, E. R.; Szabadi, E.

doi:10.2174/157015908785777193

Cited by 381 publications

(359 citation statements)

References 468 publications

(617 reference statements)

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“…A considerable amount of literature has demonstrated that the LC plays an important role in coordinating behavioral state and arousal with adaptive changes in physiology (38,39). Activity in the LC mirrors behavioral state, with increased arousal and taskrelated behavior correlating with an increased firing rate of LC neurons (40).…”

Section: Resultsmentioning

confidence: 99%

Microdissection of neural networks by conditional reporter expression from a Brainbow herpesvirus

Card

Kobiler

McCambridge

et al. 2011

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

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Transneuronal transport of neurotropic viruses is widely used to define the organization of neural circuitry in the mature and developing nervous system. However, interconnectivity within complex circuits limits the ability of viral tracing to define connections specifically linked to a subpopulation of neurons within a network. Here we demonstrate a unique viral tracing technology that highlights connections to defined populations of neurons within a larger labeled network. This technology was accomplished by constructing a replication-competent strain of pseudorabies virus (PRV-263) that changes the profile of fluorescent reporter expression in the presence of Cre recombinase (Cre). The viral genome carries a Brainbow cassette that expresses a default red reporter in infected cells. However, in the presence of Cre, the red reporter gene is excised from the genome and expression of yellow or cyan reporters is enabled. We used PRV-263 in combination with a unique lentivirus vector that produces Cre expression in catecholamine neurons. Projection-specific infection of central circuits containing these Cre-expressing catecholamine neurons with PRV-263 resulted in Cre-mediated recombination of the PRV-263 genome and conditional expression of cyan/yellow reporters. Replication and transneuronal transport of recombined virus produced conditional reporter expression in neurons synaptically linked to the Cre-expressing catecholamine neurons. This unique technology highlights connections specific to phenotypically defined neurons within larger networks infected by retrograde transneuronal transport of virus from a defined projection target. The availability of other technologies that restrict Cre expression to defined populations of neurons indicates that this approach can be widely applied across functionally defined systems.

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Section: Resultsmentioning

confidence: 99%

Microdissection of neural networks by conditional reporter expression from a Brainbow herpesvirus

Card

Kobiler

McCambridge

et al. 2011

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

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“…With drowsiness the firing declines below 1Hz and decline even further during slow wave sleep. The evidence for NA's role in arousal is abundant, consistent and strong and does not have to be reviewed here as it is well reviewed elsewhere ,Samuels and Szabadi, 2008,Sara, 2009.…”

Section: Arousal/alertnessmentioning

confidence: 99%

A right hemisphere role in cognitive reserve

Robertson

2014

Neurobiology of Aging

125

149

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High levels of education, occupational complexity and/or premorbid intelligence are associated with lower levels of cognitive impairment than would be expected from a given brain pathology. This has been observed across a range of conditions including Alzheimer's Disease (Roe, et al., 2010), stroke (Ojala-Oksala, et al., 2012), traumatic brain injury (Kesler, et al., 2003), and penetrating brain injury (Grafman, 1986). This cluster of factors, which seemingly protect the brain from expressing symptoms of damage, has been termed 'cognitive reserve' (Stern, 2012). The current review considers one possible neural network which may contribute to cognitive reserve. Based on evidence that the neurotransmitter noradrenaline mediates cognitive reserve's protective effects (Robertson, 2013) this review identifies the neurocognitive correlates of noradrenergic (NA) activity. These involve a set of inter-related cognitive processes (arousal, sustained attention, response to novelty and awareness) with a strongly right hemisphere, fronto-parietal localization, along with working memory which is also strongly modulated by NA. It is proposed that this set of processes is one plausible candidate for partially mediating the protective effects of cognitive reserve. In addition to its biological effects on brain structure and function, NA function may also facilitate networks for arousal, novelty, attention, awareness and working memory which collectively provide for a set of additional, cognitive, mechanisms that help the brain adapt to age-related changes and disease. It is hypothesized that to the extent that the lateral surface of the right prefrontal lobe and/or the right inferior parietal lobe maintain structural (white and grey matter) and functional integrity and connectivity, cognitive reserve should benefit and behavioral expression of pathological damage should thus be mitigated.

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“…Converging evidence from electrophysiology (e.g., Rajkowski, Kubiak, & Aston-Jones, 1994) and pharmacology (e.g., Phillips, Szabadi, & Bradshaw, 2000;Koss, 1986) also suggests that pupil diameter correlates with LC activity in animals. The anatomical pathways linking the LC and the pupil are a topic of ongoing research but probably involve α 2 -adrenoreceptormediated inhibition of the parasympathetic EdingerWestphal nucleus responsible for pupil constriction (Samuels & Szabadi, 2008).…”

Section: Introductionmentioning

confidence: 99%

Pupil Diameter Tracks the Exploration–Exploitation Trade-off during Analogical Reasoning and Explains Individual Differences in Fluid Intelligence

Hayes¹,

Petrov²

2016

Journal of Cognitive Neuroscience

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Abstract■ The ability to adaptively shift between exploration and exploitation control states is critical for optimizing behavioral performance. Converging evidence from primate electrophysiology and computational neural modeling has suggested that this ability may be mediated by the broad norepinephrine projections emanating from the locus coeruleus (LC) [Aston-Jones, G., & Cohen, J. D. An integrative theory of locus coeruleus-norepinephrine function: Adaptive gain and optimal performance. Annual Review of Neuroscience, 28, 403-450, 2005]. There is also evidence that pupil diameter covaries systematically with LC activity. Although imperfect and indirect, this link makes pupillometry a useful tool for studying the locus coeruleus norepinephrine system in humans and in high-level tasks. Here, we present a novel paradigm that examines how the pupillary response during exploration and exploitation covaries with individual differences in fluid intelligence during analogical reasoning on Raven's Advanced Progressive Matrices. Pupillometry was used as a noninvasive proxy for LC activity, and concurrent think-aloud verbal protocols were used to identify exploratory and exploitative solution periods. This novel combination of pupillometry and verbal protocols from 40 participants revealed a decrease in pupil diameter during exploitation and an increase during exploration. The temporal dynamics of the pupillary response was characterized by a steep increase during the transition to exploratory periods, sustained dilation for many seconds afterward, and followed by gradual return to baseline. Moreover, the individual differences in the relative magnitude of pupillary dilation accounted for 16% of the variance in Advanced Progressive Matrices scores. Assuming that pupil diameter is a valid index of LC activity, these results establish promising preliminary connections between the literature on locus coeruleus norepinephrine-mediated cognitive control and the literature on analogical reasoning and fluid intelligence. ■

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Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

Cited by 381 publications

References 468 publications

Microdissection of neural networks by conditional reporter expression from a Brainbow herpesvirus

Microdissection of neural networks by conditional reporter expression from a Brainbow herpesvirus

A right hemisphere role in cognitive reserve

Pupil Diameter Tracks the Exploration–Exploitation Trade-off during Analogical Reasoning and Explains Individual Differences in Fluid Intelligence

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