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      Pupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex

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          Abstract

          Rapid variations in cortical state during wakefulness have a strong influence on neural and behavioural responses and are tightly coupled to changes in pupil size across species. However, the physiological processes linking cortical state and pupil variations are largely unknown. Here we demonstrate that these rapid variations, during both quiet waking and locomotion, are highly correlated with fluctuations in the activity of corticopetal noradrenergic and cholinergic projections. Rapid dilations of the pupil are tightly associated with phasic activity in noradrenergic axons, whereas longer-lasting dilations of the pupil, such as during locomotion, are accompanied by sustained activity in cholinergic axons. Thus, the pupil can be used to sensitively track the activity in multiple neuromodulatory transmitter systems as they control the state of the waking brain.

          Abstract

          In addition to light intensity, changes in pupil diameter are correlated with mental effort, attention and levels of arousal. Reimer et al. report that across behavioural states, fluctuations in pupil diameter are highly correlated with activity of noradrenergic and cholinergic projection neurons.

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          Most cited references62

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          Ultra-sensitive fluorescent proteins for imaging neuronal activity

          Summary Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultra-sensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies, and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5 - 40 micrometers long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
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            Spectrum estimation and harmonic analysis

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              An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance.

              Historically, the locus coeruleus-norepinephrine (LC-NE) system has been implicated in arousal, but recent findings suggest that this system plays a more complex and specific role in the control of behavior than investigators previously thought. We review neurophysiological and modeling studies in monkey that support a new theory of LC-NE function. LC neurons exhibit two modes of activity, phasic and tonic. Phasic LC activation is driven by the outcome of task-related decision processes and is proposed to facilitate ensuing behaviors and to help optimize task performance (exploitation). When utility in the task wanes, LC neurons exhibit a tonic activity mode, associated with disengagement from the current task and a search for alternative behaviors (exploration). Monkey LC receives prominent, direct inputs from the anterior cingulate (ACC) and orbitofrontal cortices (OFC), both of which are thought to monitor task-related utility. We propose that these frontal areas produce the above patterns of LC activity to optimize utility on both short and long timescales.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                08 November 2016
                2016
                : 7
                : 13289
                Affiliations
                [1 ]Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza , Houston, Texas 77030, USA
                [2 ]Department of Neuroscience, Yale University , 333 Cedar Street, New Haven, Connecticut 06510, USA
                [3 ]Department of Biomedical Engineering, Columbia University , 1210 Amsterdam Avenue, New York, New York 10027, USA
                [4 ]Department of Electrical and Computer Engineering, Rice University , 6100 Main St, Houston, Texas 77005, USA
                Author notes
                [*]

                These authors contributed equally to this work

                Article
                ncomms13289
                10.1038/ncomms13289
                5105162
                27824036
                6e32101b-e94c-42ed-b764-f982115ef319
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 06 May 2016
                : 20 September 2016
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