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      Cholinergic Potentiation Alters Perceptual Eye Dominance Plasticity Induced by a Few Hours of Monocular Patching in Adults

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          Abstract

          A few hours of monocular deprivation with a diffuser eye patch temporarily strengthens the contribution of the deprived eye to binocular vision. This shift in favor of the deprived eye is characterized as a form of adult visual plasticity. Studies in animal and human models suggest that neuromodulators can enhance adult brain plasticity in general. Specifically, acetylcholine has been shown to improve certain aspects of visual function and plasticity in adulthood. We investigated whether a single administration of donepezil (a cholinesterase inhibitor) could further augment the temporary shift in perceptual eye dominance that occurs after 2 h of monocular patching. Twelve healthy adults completed two experimental sessions while taking either donepezil (5 mg, oral) or a placebo (lactose) pill. We measured perceptual eye dominance using a binocular phase combination task before and after 2 h of monocular deprivation with a diffuser eye patch. Participants in both groups demonstrated a significant shift in favor of the patched eye after monocular deprivation, however our results indicate that donepezil significantly reduces the magnitude and duration of the shift. We also investigated the possibility that donepezil reduces the amount of time needed to observe a shift in perceptual eye dominance relative to placebo control. For this experiment, seven subjects completed two sessions where we reduced the duration of deprivation to 1 h. Donepezil reduces the magnitude and duration of the patching-induced shift in perceptual eye dominance in this experiment as well. To verify whether the effects we observed using the binocular phase combination task were also observable in a different measure of sensory eye dominance, six subjects completed an identical experiment using a binocular rivalry task. These results also indicate that cholinergic enhancement impedes the shift that results from short-term deprivation. In summary, our study demonstrates that enhanced cholinergic potentiation interferes with the consolidation of the perceptual eye dominance plasticity induced by several hours of monocular deprivation.

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          Most cited references55

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          Short-term synaptic plasticity.

          Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca(2+)]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases of synaptic enhancement, as well as the interpretation of statistical changes in transmitter release and roles played by other factors such as alterations in presynaptic Ca(2+) influx or postsynaptic levels of [Ca(2+)]i. Synaptic depression dominates enhancement at many synapses. Depression is usually attributed to depletion of some pool of readily releasable vesicles, and various forms of the depletion model are discussed. Depression can also arise from feedback activation of presynaptic receptors and from postsynaptic processes such as receptor desensitization. In addition, glial-neuronal interactions can contribute to short-term synaptic plasticity. Finally, we summarize the recent literature on putative molecular players in synaptic plasticity and the effects of genetic manipulations and other modulatory influences.
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            Inhibitory threshold for critical-period activation in primary visual cortex.

            Neuronal circuits across several systems display remarkable plasticity to sensory input during postnatal development. Experience-dependent refinements are often restricted to well-defined critical periods in early life, but how these are established remains mostly unknown. A representative example is the loss of responsiveness in neocortex to an eye deprived of vision. Here we show that the potential for plasticity is retained throughout life until an inhibitory threshold is attained. In mice of all ages lacking an isoform of GABA (gamma-aminobutyric acid) synthetic enzyme (GAD65), as well as in immature wild-type animals before the onset of their natural critical period, benzodiazepines selectively reduced a prolonged discharge phenotype to unmask plasticity. Enhancing GABA-mediated transmission early in life rendered mutant animals insensitive to monocular deprivation as adults, similar to normal wild-type mice. Short-term presynaptic dynamics reflected a synaptic reorganization in GAD65 knockout mice after chronic diazepam treatment. A threshold level of inhibition within the visual cortex may thus trigger, once in life, an experience-dependent critical period for circuit consolidation, which may otherwise lie dormant.
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              Cortical remodelling induced by activity of ventral tegmental dopamine neurons.

              Representations of sensory stimuli in the cerebral cortex can undergo progressive remodelling according to the behavioural importance of the stimuli. The cortex receives widespread projections from dopamine neurons in the ventral tegmental area (VTA), which are activated by new stimuli or unpredicted rewards, and are believed to provide a reinforcement signal for such learning-related cortical reorganization. In the primary auditory cortex (AI) dopamine release has been observed during auditory learning that remodels the sound-frequency representations. Furthermore, dopamine modulates long-term potentiation, a putative cellular mechanism underlying plasticity. Here we show that stimulating the VTA together with an auditory stimulus of a particular tone increases the cortical area and selectivity of the neural responses to that sound stimulus in AI. Conversely, the AI representations of nearby sound frequencies are selectively decreased. Strong, sharply tuned responses to the paired tones also emerge in a second cortical area, whereas the same stimuli evoke only poor or non-selective responses in this second cortical field in naive animals. In addition, we found that strong long-range coherence of neuronal discharge emerges between AI and this secondary auditory cortical area.
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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
                31 January 2019
                2019
                : 13
                : 22
                Affiliations
                [1] 1McGill Vision Research Unit, Department of Ophthalmology, McGill University , Montréal, QC, Canada
                [2] 2Laboratoire de Neurobiologie de la Cognition Visuelle, École d'Optométrie, Université de Montréal , Montréal, QC, Canada
                [3] 3Douglas Mental Health University Institute, McGill University , Montréal, QC, Canada
                Author notes

                Edited by: Qasim Zaidi, University at Buffalo, United States

                Reviewed by: Gregor Rainer, Université de Fribourg, Switzerland; Hirofumi Morishita, Icahn School of Medicine at Mount Sinai, United States

                *Correspondence: Robert F. Hess robert.hess@ 123456mcgill.ca

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

                Article
                10.3389/fnins.2019.00022
                6365463
                30766471
                e668f42e-0ec3-4579-8635-8ac9067db3e5
                Copyright © 2019 Sheynin, Chamoun, Baldwin, Rosa-Neto, Hess and Vaucher.

                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
                : 25 July 2018
                : 10 January 2019
                Page count
                Figures: 4, Tables: 3, Equations: 4, References: 63, Pages: 12, Words: 9862
                Funding
                Funded by: Canadian Institutes of Health Research 10.13039/501100000024
                Award ID: CCI-125686
                Award ID: CCI-228103
                Award ID: MOP-111003
                Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
                Award ID: 238835-2011
                Categories
                Neuroscience
                Original Research

                Neurosciences
                neural plasticity,donepezil,neuromodulators,short-term monocular deprivation,cholinergic enhancement,ocular dominance,excitatory/inhibitory balance

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