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      Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems

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          Abstract

          After sensory information is encoded into neural signals at the periphery, it is processed through multiple brain regions before perception occurs (i.e., sensory processing). Recent work has begun to tease apart how neuromodulatory systems influence sensory processing. Vagus nerve stimulation (VNS) is well-known as an effective and safe method of activating neuromodulatory systems. There is a growing body of studies confirming VNS has immediate effects on sensory processing across multiple sensory modalities. These immediate effects of VNS on sensory processing are distinct from the more well-documented method of inducing lasting neuroplastic changes to the sensory pathways through repeatedly delivering a brief VNS burst paired with a sensory stimulus. Immediate effects occur upon VNS onset, often disappear upon VNS offset, and the modulation is present for all sensory stimuli. Conversely, the neuroplastic effect of pairing sub-second bursts of VNS with a sensory stimulus alters sensory processing only after multiple pairing sessions, this alteration remains after cessation of pairing sessions, and the alteration selectively affects the response properties of neurons encoding the specific paired sensory stimulus. Here, we call attention to the immediate effects VNS has on sensory processing. This review discusses existing studies on this topic, provides an overview of the underlying neuromodulatory systems that likely play a role, and briefly explores the potential translational applications of using VNS to rapidly regulate sensory processing.

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          Most cited references215

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          The locus coeruleus and noradrenergic modulation of cognition.

          Susan Sara (2009)
          Mood, attention and motivation co-vary with activity in the neuromodulatory systems of the brain to influence behaviour. These psychological states, mediated by neuromodulators, have a profound influence on the cognitive processes of attention, perception and, particularly, our ability to retrieve memories from the past and make new ones. Moreover, many psychiatric and neurodegenerative disorders are related to dysfunction of these neuromodulatory systems. Neurons of the brainstem nucleus locus coeruleus are the sole source of noradrenaline, a neuromodulator that has a key role in all of these forebrain activities. Elucidating the factors that control the activity of these neurons and the effect of noradrenaline in target regions is key to understanding how the brain allocates attention and apprehends the environment to select, store and retrieve information for generating adaptive behaviour.
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            Pupil fluctuations track fast switching of cortical states during quiet wakefulness.

            Neural responses are modulated by brain state, which varies with arousal, attention, and behavior. In mice, running and whisking desynchronize the cortex and enhance sensory responses, but the quiescent periods between bouts of exploratory behaviors have not been well studied. We found that these periods of "quiet wakefulness" were characterized by state fluctuations on a timescale of 1-2 s. Small fluctuations in pupil diameter tracked these state transitions in multiple cortical areas. During dilation, the intracellular membrane potential was desynchronized, sensory responses were enhanced, and population activity was less correlated. In contrast, constriction was characterized by increased low-frequency oscillations and higher ensemble correlations. Specific subtypes of cortical interneurons were differentially activated during dilation and constriction, consistent with their participation in the observed state changes. Pupillometry has been used to index attention and mental effort in humans, but the intracellular dynamics and differences in population activity underlying this phenomenon were previously unknown.
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              Modulation of visual responses by behavioral state in mouse visual cortex.

              Studies of visual processing in rodents have conventionally been performed on anesthetized animals, precluding examination of the effects of behavior on visually evoked responses. We have now studied the response properties of neurons in primary visual cortex of awake mice that were allowed to run on a freely rotating spherical treadmill with their heads fixed. Most neurons showed more than a doubling of visually evoked firing rate as the animal transitioned from standing still to running, without changes in spontaneous firing or stimulus selectivity. Tuning properties in the awake animal were similar to those measured previously in anesthetized animals. Response magnitude in the lateral geniculate nucleus did not increase with locomotion, demonstrating that the striking change in responsiveness did not result from peripheral effects at the eye. Interestingly, some narrow-spiking cells were spontaneously active during running but suppressed by visual stimuli. These results demonstrate powerful cell-type-specific modulation of visual processing by behavioral state in awake mice.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                05 July 2022
                2022
                : 16
                : 922424
                Affiliations
                [1] 1Department of Biomedical Engineering, Columbia University , New York, NY, United States
                [2] 2Jacobs Technion-Cornell Institute, Cornell Tech , New York, NY, United States
                [3] 3Department of Neurology and Orthopedics, Columbia University Medical Center , New York, NY, United States
                Author notes

                Edited by: Julian Keil, University of Kiel, Germany

                Reviewed by: Huizhong Whit Tao, University of Southern California, United States; Jiayue Cao, University of Michigan, United States; Rimenez Rodrigues de Souza, The University of Texas at Dallas, United States

                *Correspondence: Charles Rodenkirch, cr585@ 123456cornell.edu

                This article was submitted to Perception Science, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2022.922424
                9294458
                35864985
                c8f8ba99-6c6a-4c85-ae65-ec7a1260b02f
                Copyright © 2022 Rodenkirch, Carmel and Wang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 April 2022
                : 15 June 2022
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 215, Pages: 14, Words: 12489
                Funding
                Funded by: National Institutes of Health, doi 10.13039/100000002;
                Award ID: NIH R01NS119813
                Award ID: NIH R01AG075114
                Award ID: NIH R01MH112267
                Funded by: National Science Foundation, doi 10.13039/100000001;
                Award ID: CBET 1847315
                Categories
                Neuroscience
                Mini Review

                Neurosciences
                vagus nerve stimulation,sensory processing,neuromodulation,cholinergic system,dopaminergic system,serotonergic system,locus coereleus,noradrenergic system

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