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      Noradrenaline Improves Behavioral Contrast Sensitivity via the β-Adrenergic Receptor

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          Abstract

          Noradrenaline (NA) is released from the locus coeruleus in the brainstem to almost the whole brain depending on the physiological state or behavioral context. NA modulates various brain functions including vision, but many questions about the functional role of its effects and mechanisms remain unclear. To explore these matters, we focused on three questions, 1) whether NA improves detectability of a behavior-relevant visual stimulus, 2) which receptor subtypes contribute to the NA effects, and 3) whether the NA effects are specific for visual features such as spatial frequency (SF). We measured contrast sensitivity in rats by a two-alternative forced choice visual detection task and tested the effects of NA receptor blockers in three SF conditions. Propranolol, a β-adrenergic receptor inhibitor, significantly decreased contrast sensitivity, but neither prazosin nor idazoxan, α 1- and α 2-adrenergic receptor inhibitors, respectively, had an effect. This β blocker effect was observed only at optimal SF. These results indicate that endogenous NA enhances visual detectability depending on stimulus spatial properties via mainly β-adrenergic receptors.

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          Most cited references18

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          Psychophysical measurement of contrast sensitivity in the behaving mouse.

          To understand how activity in mammalian neural circuits controls behavior, the mouse is a promising model system due to the convergence of genetic, optical, and physiological methods. The ability to control and quantify behavior precisely is also essential for these studies. We developed an operant visual detection paradigm to make visual psychophysical measurements: head-fixed mice make responses by pressing a lever. We designed this task to permit neurophysiological studies of behavior in cerebral cortex, where activity is variable from trial to trial and neurons encode many types of information simultaneously. To study neural responses in the face of this complexity, we trained mice to do a task where they perform hundreds of trials daily and perceptual thresholds can be measured. We used this task to measure both visual acuity and the minimum detectable contrast in behaving mice. We found that the mouse contrast response function is similar in shape to other species. They can detect low-contrast stimuli, with a peak contrast threshold of 2%, equivalent to ∼15° eccentric in human vision. Mouse acuity is modest, with an upper limit near 0.5 cycles/°, consistent with prior data.
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            Locus coeruleus activity in monkey: phasic and tonic changes are associated with altered vigilance.

            Impulse activity of individual neurons in the nucleus locus coeruleus (LC) was recorded from chair-restrained, unanesthetized cynomolgus monkeys. LC activity was closely related to the behavioral state of the animal. In alert waking, LC neurons displayed continuous, moderately irregular activity. In contrast, prolonged pauses in activity accompanied drowsiness. These pauses preceded eye closure and occurred 1-3 s before the onset of slow-wave EEG. At awakening, LC activation preceded by up to 3 s desynchronized EEG and eye opening. LC activity during alertness varied tonically. During behavioral agitation LC activity was higher than during goal-directed task behavior (described below). In addition to these changes in tonic activity, LC neurons were also phasically responsive to certain sensory stimuli. These cells responded selectively to unexpected, meaningful sounds. LC neurons were also recorded during a visual oddball discrimination task in which the monkey was required to selectively release a lever in response to an infrequent visual cue (target cue; CS+) to receive juice reward. LC neurons were selectively activated by CS+ cues in this task; no other task events evoked LC activity. The mean latency of CS+ response was 108 ms (90 ms for multicell recordings), more than 150 ms prior to the behavioral response (lever release). These responses became smaller in later epochs during the session, along with deteriorating task performance. It is proposed that these short-lasting stimulus-evoked LC responses may help optimize behavioral responses and increase vigilance to subsequent sensory stimuli. Together, LC may contribute both to maintaining tonic levels of vigilance and to phasically modulating the current vigilance level in a stimulus-dependent mode.
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              Activation of the noradrenergic system facilitates an attentional shift in the rat.

              The noradrenergic system was pharmacologically activated with the alpha 2 receptor antagonist, idazoxan (2 mg/kg i.p.), during the acquisition of a complex appetitive task requiring a shift in attention to stimulus dimension and in response strategy. Rats first learned a fixed path of 6 successive choices in a linear maze. The task was then changed to a visual discrimination task in which the spatial configuration of the correct path was indicated by visual cues and changed on each daily trial. During this part of the task, the rats were injected before each trial with idazoxan, a drug which increases the firing rate of neurons in the locus coeruleus and the release of noradrenaline in the cortex and hippocampus. Two control experiments showed that the drug treatment had no effect on the acquisition of either component of the task - the successive place learning or the visual discrimination. The drug was found to be effective only during the shift phase of the experiment, the idazoxan-treated rats taking fewer trials to reach criterion than the saline. A second experiment showed that idazoxan increased the amount of time spent investigating novel and unexpected objects in a familiar hole board. These results implicate the noradrenergic system in problem-solving which requires an attentional shift or a shift in responding from familiar to novel stimuli.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 December 2016
                2016
                : 11
                : 12
                : e0168455
                Affiliations
                [1 ]Laboratory of Cognitive and Behavioral Neuroscience, Graduate School of Frontier Bioscience, Osaka University, Suita, Osaka, Japan
                [2 ]Laboratory of Cognitive and Behavioral Neuroscience, Graduate School of Medicine, Osaka University, Toyonaka, Osaka, Japan
                Universidad de Salamanca, SPAIN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: RM S. Shimegi.

                • Data curation: RM.

                • Formal analysis: RM.

                • Funding acquisition: S. Shimegi.

                • Investigation: RM S. Shimegi.

                • Methodology: RM S. Soma NS.

                • Project administration: S. Shimegi.

                • Resources: S. Shimegi.

                • Software: RM NS S. Soma.

                • Supervision: S. Shimegi.

                • Visualization: RM.

                • Writing – original draft: RM S. Shimegi.

                • Writing – review & editing: RM S. Shimegi.

                [¤a]

                Current address: Brain Science Institute, Tamagawa University, Tamagawa, Tokyo, Japan

                [¤b]

                Current address: Graduate School of Engineering, Osaka University, Suita, Osaka, Japan

                Article
                PONE-D-16-15938
                10.1371/journal.pone.0168455
                5161482
                27992510
                e220c6f2-25eb-4fba-bc80-0392b11df577
                © 2016 Mizuyama et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 April 2016
                : 30 November 2016
                Page count
                Figures: 3, Tables: 0, Pages: 10
                Funding
                This work was supported by KAKENHI ( http://www.mext.go.jp/english/), 22500573, 25282216, 25560302, and 16H01869 to S.Shimegi.
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