A nutriepigenetic pathway links nutrient information to sensory plasticity

Diet composition has a profound influence on brain physiology and behavior, but the mechanisms through which nutrient information is transmuted into neural changes remain elusive. Here we uncover how the metabolic enzyme O-GlcNAc Transferase (OGT) transforms information about the dietary environment into taste adaptations. We show that in the fly D. melanogaster, OGT decorates the chromatin of the sweet taste neurons and provides the nutrient context to drive changes in chromatin accessibility in response to high dietary sugar. Specifically, we found that OGT cooperates with the epigenetic silencer Polycomb Repressive Complex 2.1 (PRC2.1) to promote nutrient-sensitive variations in chromatin openness; these chromatin dynamics result in changes in gene expression and taste plasticity that are dependent on the catalytic activity of OGT. Parallel nutrigenomic signatures were also observed in the lingual epithelium of rats exposed to high dietary sugar, suggesting that this conserved metabolic-epigenetic pathway may also underlie diet-dependent taste changes in mammals. Together our findings reveal a novel role for nutriepigenetic signaling in the brain: amplifying nutrient perturbations into robust changes in chromatin accessibility and transcriptional output that shape neural and behavioral plasticity.

Hearing Gloves and Seeing Tongues? Disability, Sensory Substitution and the Origins of the Neuroplastic Subject

Researchers in post-war industrial laboratories such as Bell Labs and the Smith-Kettlewell Institute pioneered solutions to compensate for sensory loss through so-called sensory substitution systems, premised on an assumption of cortical and sensory plasticity. The article tracks early discussions of plasticity in psychology literature from William James, acknowledged by Wiener, but explicitly developed by Bach-y-Rita and his collaborators. After discussing the conceptual foundations of the principles of sensory substitution, two examples are discussed. First, ‘Project Felix’ was an experiment in vibrotactile communication by means of ‘hearing gloves’ for the deaf at Norbert Wiener’s laboratory at Massachusetts Institute of Technology, demonstrated to Helen Keller in 1950. Second, the tactile-visual sensory substitution system for the blind pioneered by Paul Bach-y-Rita from 1968 onwards. Cumulatively, this article underlines the crucial yet occluded history of research on sensory impairments in the discovery of underlying neurophysiological processes of plasticity and the emergent discourse of neuroplastic subjectivity.

Dopamine enhanced auditory perceptual learning in humans via long-term memory consolidation

Dopamine is known to modulate sensory plasticity in animal brain, but how it impacts perceptual learning in humans remains largely unknown. In a placebo-controlled, double-blinded training experiment with young healthy adults (both male and female), oral administration of Madopar, a dopamine precursor, during each of multiple training sessions was shown to enhance auditory perceptual learning, particularly in late training sessions. Madopar also enhanced learning and transfer to working memory when tested outside the time widow of drug effect, which appeared to retain for at least 20 days. To test whether such learning modulation was mediated by the dopaminergic working memory network, the same dopamine manipulation was applied to working memory training, but to little influence on learning or transfer. Further, a neural network model of auditory perceptual learning revealed distinctive behavioural modulation patterns for proposed dopaminergic functions in the auditory cortex: trial-by-trial reinforcement signals (reward/reward prediction error and expected reward) and across-session memory consolidation. Only the memory consolidation simulations matched experimental observations. The results thus demonstrate that dopamine modulates human perceptual learning, mostly likely via enhancing memory consolidation over extended time scales.

Functional reallocation of sensory processing resources caused by long-term neural adaptation to altered optics

The eye’s optics are a major determinant of visual perception. Elucidating how long-term exposure to optical defects affects visual processing is key to understanding the capacity for, and limits of, sensory plasticity. Here, we show evidence of functional reallocation of sensory processing resources following long-term exposure to poor optical quality. Using adaptive optics to bypass all optical defects, we assessed visual processing in neurotypically-developed adults with healthy eyes and with keratoconus – a corneal disease causing severe optical aberrations. Under fully-corrected optical conditions, keratoconus patients showed altered contrast sensitivity, with impaired sensitivity for fine spatial details and better-than-typical sensitivity for coarse spatial details. Both gains and losses in sensitivity were more pronounced in patients experiencing poorer optical quality in their daily life and mediated by changes in signal enhancement mechanisms. These findings show that adult neural processing adapts to better match the changes in sensory inputs caused by long-term exposure to altered optics.

Audiovisual adaptation is expressed in spatial and decisional codes

The brain adapts dynamically to the changing sensory statistics of its environment. The neural circuitries and representations that support this cross-sensory plasticity remain unknown. We combined psychophysics and model-based representational fMRI and EEG to characterize how the adult human brain adapts to misaligned audiovisual signals. We show that audiovisual adaptation moulds regional BOLD-responses and fine-scale activity patterns in a widespread network from Heschl’s gyrus to dorsolateral prefrontal cortices. Crucially, audiovisual recalibration relies on distinct spatial and decisional codes that are expressed with opposite gradients and timecourses across the auditory processing hierarchy. Early activity patterns in auditory cortices encode sounds in a continuous space that flexibly adapts to misaligned visual inputs. Later activity patterns in frontoparietal cortices code decisional uncertainty consistent with these spatial transformations. Our findings demonstrate that regions throughout the auditory processing hierarchy multiplex spatial and decisional codes to adapt flexibly to the changing sensory statistics in the environment.

Plasticity in perception: insights from color vision deficiencies

Inherited color vision deficiencies typically result from a loss or alteration of the visual photopigments absorbing light and thus impact the very first step of seeing. There is growing interest in how subsequent steps in the visual pathway might be calibrated to compensate for the altered receptor signals, with the possibility that color coding and color percepts might be less severely impacted than the receptor differences predict. These compensatory adjustments provide important insights into general questions about sensory plasticity and the sensory and cognitive processes underlying how we experience color.

Thyroid hormone receptors mediate two distinct mechanisms of long-wavelength vision

Thyroid hormone (TH) signaling plays an important role in the regulation of long-wavelength vision in vertebrates. In the retina,thyroid hormone receptor β(thrb) is required for expression of long-wavelength-sensitive opsin (lws) in red cone photoreceptors, while in retinal pigment epithelium (RPE), TH regulates expression of a cytochrome P450 enzyme,cyp27c1, that converts vitamin A1into vitamin A2to produce a red-shifted chromophore. To better understand how TH controls these processes, we analyzed the phenotype of zebrafish with mutations in the three known TH nuclear receptor transcription factors (thraa,thrab,and thrb). We found that no single TH nuclear receptor is required for TH-mediated induction ofcyp27c1but that deletion of all three (thraa−/−;thrab−/−;thrb−/−) completely abrogates its induction and the resulting conversion of A1- to A2-based retinoids. In the retina, loss ofthrbresulted in an absence of red cones at both larval and adult stages without disruption of the underlying cone mosaic. RNA-sequencing analysis revealed significant down-regulation of only five genes in adultthrb−/−retina, of which three (lws1,lws2, andmiR-726) occur in a single syntenic cluster. In thethrb−/−retina, retinal progenitors destined to become red cones were transfated into ultraviolet (UV) cones and horizontal cells. Taken together, our findings demonstrate cooperative regulation ofcyp27c1by TH receptors and a requirement forthrbin red cone fate determination. Thus, TH signaling coordinately regulates both spectral sensitivity and sensory plasticity.

Recurrent processing drives experience-dependent plasticity for perceptual decisions

Learning and experience are critical for translating ambiguous sensory information from our environments to perceptual decisions. Yet, evidence on how training molds the adult human brain remains controversial, as fMRI at standard resolution does not allow us to discern the finer-scale mechanisms that underlie sensory plasticity. Here, we combine ultra-high field (7T) functional imaging at sub-millimetre resolution with orientation discrimination training to interrogate experience-dependent plasticity across cortical depths. Our results provide evidence for recurrent plasticity, by contrast to sensory encoding vs. feedback mechanisms. We demonstrate that learning alters orientation-specific representations in superficial rather than middle V1 layers, suggesting changes in read-out rather than input signals. Further, learning increases feedforward rather than feedback layer-to-layer connectivity in occipito-parietal regions, suggesting that sensory plasticity gates perceptual decisions. Our findings propose finer-scale plasticity mechanisms that re-weight sensory signals to inform improved decisions, bridging the gap between micro- and macro-circuits of experience-dependent plasticity.