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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 829 records · Page 46Linked to original sources

bioRxiv2016

Long-term, layer-specific modification of spontaneous activity in the mouse somatosensory cortex following sensory stimulation

Neocortical circuits exhibit spontaneous neuronal activity whose functional relevance remains enigmatic. Several proposed functions assume that sensory experience can influence subsequent spontaneous activity. However, long-term alterations in spontaneous firing rates following sensory stimulation have not been reported until now. Here we show that multi-whisker, spatiotemporally rich stimulation of mouse vibrissae induces a laminar-specific, long-term increase of spontaneous activity in the somatosensory cortex. Such stimulation additionally produces stereotypical neural ensemble firing patterns from simultaneously recorded single neurons, which are maintained during spontaneous activity following stimulus offset. The increased neural activity and concomitant ensemble firing patterns are sustained for at least 25 minutes after stimulation, and specific to layers IV and Vb. In contrast, the same stimulation protocol applied to a single whisker fails to elicit this effect. Since layer Vb has the largest receptive fields and, together with layer IV, receives direct thalamic and lateral drive, the increase in firing activity could be the result of mechanisms involving the integration of spatiotemporal patterns across multiple whiskers. Our results provide direct evidence of modification of spontaneous cortical activity by sensory stimulation and could offer insight into the role of spatiotemporal integration in memory storage mechanisms for complex stimuli.

Neuroscience↗

bioRxiv2016

Mechanical flexibility reduces the foreign body response to long- term implanted microelectrodes in rabbit cortex

Micromotion between the brain and implanted electrodes is a major contributor to the failure of invasive microelectrodes. Movements of the electrode tip cause recording instabilities while spike amplitudes decline over the weeks/months post-implantation due to glial cell activation caused by sustained mechanical trauma. We compared the glial response over a 26-96 week period following implantation in the rabbit cortex of microwires and a novel flexible electrode. Horizontal sections were used to obtain a depth profile of the radial distribution of microglia, astrocytes and neurofilament. We found that the flexible electrode was associated with decreased gliosis compared to the microwires over these long indwelling periods. This was in part due to a decrease in overall microgliosis and enhanced neuronal density around the flexible probe, especially at longer periods of implantation.

Neuroscience↗

bioRxiv2016

Auditory Nerve Stochasticity Impedes Category Learning: the Role of Cochlear Nucleus and Inferior Colliculus in Stabilising Auditory Nerve Firing

It is well known that auditory nerve (AN) fibers overcome bandwidth limitations through the \"volley principle\", a form of multiplexing. What is less well known is that the volley principle introduces a degree of unpredictability into AN neural firing patterns which makes even simple stimulus categorization tasks difficult. We use a physiologically grounded, unsupervised spiking neural network model of the auditory brain with STDP learning to demonstrate that plastic auditory cortex is unable to learn even simple auditory object categories when exposed to the raw AN firing input without subcortical preprocessing. We then demonstrate the importance of non-plastic subcortical preprocessing within the cochlear nucleus (CN) and the inferior colliculus (IC) for stabilising and denoising AN responses. Such preprocessing enables the plastic auditory cortex to learn efficient robust representations of the auditory object categories. The biological realism of our model makes it suitable for generating neurophysiologically testable hypotheses.

Neuroscience↗

bioRxiv2016

Fractured tonotopy of functional neural clusters in mouse auditory cortex

The degree of order versus randomness in mammalian cortical circuits has been the subject of much discussion. Previous reports showed that at a large scale there is smooth tonotopy in mouse auditory cortex, while at the single neuron level the representation is the traditional \"salt and pepper\" configuration attributed to rodent cortex. Here we show that at the micro columnar scale we find a large variety of response profiles, but neurons tend to share similar preference in terms of frequency, bandwidth and latency. However, this smooth representation was fractured and large differences were possible between neighbouring neurons. Despite the tendency of most groups of neurons to operate redundantly, high information gains were achieved between cells that had a high signal correlation. Connectivity between neurons was highly non-random, in agreement with a previous in-vitro report from layer five. Our results suggest the existence of functional clusters, connecting neighbouring mini-columns. This supports the idea of a \"salt and pepper\" configuration at the level of functional clusters of neurons rather than single units.

Neuroscience↗

bioRxiv2016

Temporal Modulations Reveal Distinct Rhythmic Properties of Speech and Music

Speech and music have structured rhythms, but these rhythms are rarely compared empirically. This study, based on large corpora, quantitatively characterizes and compares a major acoustic correlate of spoken and musical rhythms, the slow (0.25-32 Hz) temporal modulations in sound intensity. We show that the speech modulation spectrum is highly consistent cross 9 languages (including languages with typologically different rhythmic characteristics, such as English, French, and Mandarin Chinese). A different, but similarly consistent modulation spectrum is observed for Western classical music played by 6 different instruments. Western music, including classical music played by single instruments, symphonic, jazz, and rock music, contains more energy than speech in the low modulation frequency range below 4 Hz. The temporal modulations of speech and music show broad but well-separated peaks around 5 and 2 Hz, respectively. These differences in temporal modulations alone, without any spectral details, can discriminate speech and music with high accuracy. Speech and music therefore show distinct and reliable statistical regularities in their temporal modulations that likely facilitate their perceptual analysis and its neural foundations.

Neuroscience↗

bioRxiv2016

A phenome-wide examination of neural and cognitive function

This data descriptor outlines a shared neuroimaging dataset from the UCLA Consortium for Neuropsychiatric Phenomics, which focused on understanding the dimensional structure of memory and cognitive control (response inhibition) functions in both healthy individuals (138 subjects) and individuals with neuropsychiatric disorders including schizophrenia (58 subjects), bipolar disorder (49 subjects), and attention deficit/hyperactivity disorder (45 subjects). The dataset includes an extensive set of task-based fMRI assessments, resting fMRI, structural MRI, and high angular resolution diffusion MRI. The dataset is shared through the OpenfMRI project, and is formatted according to the Brain Imaging Data Structure (BIDS) standard.

Neuroscience↗

bioRxiv2016

Firing patterns of serotonin neurons underlying cognitive flexibility

Serotonin is implicated in mood and affective disorders1,2 but growing evidence suggests that its core endogenous role may be to promote flexible adaptation to changes in the causal structure of the environment3-8. This stems from two functions of endogenous serotonin activation: inhibiting learned responses that are not currently adaptive9,10 and driving plasticity to reconfigure them1113. These mirror dual functions of dopamine in invigorating reward-related responses and promoting plasticity that reinforces new ones16,17. However, while dopamine neurons are known to be activated by reward prediction errors18,19, consistent with theories of reinforcement learning, the reported firing patterns of serotonin neurons21-23 do not accord with any existing theories1,24,25. Here, we used long-term photometric recordings in mice to study a genetically-defined population of dorsal raphe serotonin neurons whose activity we could link to normal reversal learning. We found that these neurons are activated by both positive and negative prediction errors, thus reporting the kind of surprise signal proposed to promote learning in conditions of uncertainty26,27. Furthermore, by comparing cue responses of serotonin and dopamine neurons we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Together, these findings show how the firing patterns of serotonin neurons support a role in cognitive flexibility and suggest a revised model of dopamine-serotonin opponency with potential clinical implications.

Neuroscience↗

bioRxiv2016

Unsupervised Learning of Temporal Features for Word Categorization in a Spiking Neural Network Model of the Auditory Brain

The nature of the code used in the auditory cortex to represent complex auditory stimuli, such as naturally spoken words, remains a matter of debate. Here we argue that such representations are encoded by stable spatio-temporal patterns of firing within cell assemblies known as polychronous groups, or PGs. We develop a physiologically grounded, unsupervised spiking neural network model of the auditory brain with local, biologically realistic, spike-time dependent plasticity (STDP) learning, and show that the plastic cortical layers of the network develop PGs which convey substantially more information about the speaker independent identity of two naturally spoken word stimuli than does rate encoding that ignores the precise spike timings. We furthermore demonstrate that such informative PGs can only develop if the input spatio-temporal spike patterns to the plastic cortical areas of the model are relatively stable.\n\nAuthor SummaryCurrently we still do not know how the auditory cortex encodes the identity of complex auditory objects, such as words, given the great variability in the raw auditory waves that correspond to the different pronunciations of the same word by different speakers. Here we argue for temporal information encoding within neural cell assemblies for representing auditory objects. Unlike the more traditionally accepted rate encoding, temporal encoding takes into account the precise relative timing of spikes across a population of neurons. We provide support for our hypothesis by building a neurophysiologically grounded spiking neural network model of the auditory brain with a biologically plausible learning mechanism. We show that the model learns to differentiate between naturally spoken digits \"one\" and \"two\" pronounced by numerous speakers in a speaker-independent manner through simple unsupervised exposure to the words. Our simulations demonstrate that temporal encoding contains significantly more information about the two words than rate encoding. We also show that such learning depends on the presence of stable patterns of firing in the input to the cortical areas of the model that are performing the learning.

Neuroscience↗

bioRxiv2016

The formation of extinction memory requires the accumulation of N6-methyl-2-deoxyadenosine in DNA

Here we report that the recently discovered mammalian DNA modification N6-methyl-2-deoxyadenosine (m6dA) is dynamically regulated in primary cortical neurons, and accumulates along promoters and coding sequences within the genome of activated prefrontal cortical neurons of adult C57/BI6 mice in response to fear extinction learning. The deposition of m6dA is generally associated with increased genome-wide occupancy of the mammalian m6dA methyltransferase, N6amt1, and this correlates with fear extinction learning-induced gene expression. Of particular relevance for fear extinction memory, the accumulation of m6dA is associated with an active chromatin state and the recruitment of transcriptional machinery to the brain-derived neurotrophic factor (Bdnf) P4 promoter, which is required for Bdnf exon IV mRNA expression and for the extinction of conditioned fear. These results expand the scope of DNA modifications in the adult brain and highlight changes in m6dA as a novel neuroepigenetic mechanism associated with activity-induced gene expression and the formation of fear extinction memory.

Neuroscience↗

bioRxiv2016

Architecture of fully occupied GluA2 AMPA receptor - TARP complex elucidated by single particle cryo-electron microscopy

Fast excitatory neurotransmission in the mammalian central nervous system is largely carried out by AMPA-sensitive ionotropic glutamate receptors. Localized within the postsynaptic density of glutamatergic spines, AMPA receptors are composed of heterotetrameric receptor assemblies associated with auxiliary subunits, the most common of which are transmembrane AMPA-receptor regulatory proteins (TARPs). The association of TARPs with AMPA receptors modulates the kinetics of receptor gating and pharmacology, as well as trafficking. Here we report the cryo-EM structure of the homomeric GluA2 AMPA receptor saturated with TARP {gamma}2 subunits, showing how the TARPs are arranged with four-fold symmetry around the ion channel domain, making extensive interactions with the M1, M2 and M4 TM helices. Poised like partially opened hands underneath the two-fold symmetric ligand binding domain (LBD) clamshells, one pair of TARPs are juxtaposed near the LBD dimer interface, while the other pair are near the LBD dimer-dimer interface. The extracellular domains of TARP are positioned to not only modulate LBD clamshell closure, but also to affect conformational rearrangements of the LBD layer associated with receptor activation and desensitization, while the TARP transmembrane (TM) domains buttress the ion channel pore.

Neuroscience↗

bioRxiv2016

Perceptual integration without conscious access

The visual system has the remarkable ability to integrate fragmentary visual input into a perceptually organized collection of surfaces and objects, a process we refer to as perceptual integration. Despite a long tradition of perception research, it is not known whether access to consciousness is required to complete perceptual integration. To investigate this question, we manipulated access to consciousness using the attentional blink. We show that behaviorally, the attentional blink impairs perceptual decisions about the presence of integrated surface structure from fragmented input. However, when applying a multivariate classifier to electroencephalogram (EEG) data, the ability to decode the presence of integrated percepts remains intact when conscious access is impaired. In contrast, when disrupting consciousness through masking, decisions about integrated percepts and decoding of integrated percepts are impaired in concert with each other, while leaving feedforward representations intact. Together, these data show a dissociation between access to consciousness and perceptual integration.\n\nSignificance statementOur brain constantly selects salient and/or goal-relevant objects from the visual environment, so that it can operate on neural representations of these objects. But what is the fate of objects that are not selected? Are these discarded, so that the brain only has an impoverished non-perceptual representation of them? Or does the brain construct perceptually rich representations, even when objects are not consciously accessed by our cognitive system? Here we answer that question by manipulating the information that enters into awareness, while simultaneously measuring cortical activity using EEG. We show that objects that do not enter consciousness can nevertheless have a neural signature that is indistinguishable from perceptually rich representations that occur for objects that do enter into conscious awareness.

Neuroscience↗

bioRxiv2016

Age-related differences in self-reported sleep quality predict healthy ageing across multiple domains: a multi-modal cohort of 2406 adults

ObjectivesTo examine age related differences in self-reported sleep quality and their associations with health outcomes across four domains: Physical Health, Cognitive Health, Mental Health and Neural Health.\n\nSettingCam-CAN is a cohort study in East Anglia/England, which collected self-reported health and lifestyle questions as well as a range of objective measures from healthy adults.\n\nParticipants2406 healthy adults (age 18-98) answered questions about their sleep quality (Pittsburgh Sleep Quality Index) and measures of Physical, Cognitive, Mental, and Neural Health. A subset of 641 individuals provided measures of brain structure.\n\nMain outcome measuresPittsburgh Sleep Quality Index scores (PSQI) of sleep, and scores across tests within the four domains of health. Latent Class Analysis (LCA) is used to identify sleep types across the lifespan. Bayesian regressions quantify the presence, and absence, of relationships between sleep quality and health measures.\n\nResultsBetter sleep is generally associated with better health outcomes, strongly so for mental health, moderately for cognitive and physical health, but not for sleep quality and neural health. Latent Class Analysis identified four sleep types: Good sleepers (68.6%, most frequent in middle age), inefficient sleepers (13.05%, most frequent in old age), Delayed sleepers (9.76%, most frequent in young adults) and poor sleepers (8.6%, most frequent in old age). There is little evidence for interactions between sleep quality and age on health outcomes. Finally, we observe u-shaped associations between sleep duration and mental health (depression and anxiety) as well as self-reported general health, such that both short and long sleep were associated with poorer outcomes.\n\nConclusionsLifespan changes in sleep quality are multifaceted and not captured well by summary measures, but instead as partially independent symptoms that vary in prevalence across the lifespan. Better self-reported sleep is associated with better health outcomes, and the strength of these associations differs across health domains. Notably, we do observed associations between self-reported sleep quality and white matter.\n\nFundingBiotechnology and Biological Sciences Research Council (grant number BB/H008217/1). RAK is supported by the Wellcome Trust (grant number 107392/Z/15/Z and the UK Medical Research Council (MC-A060-5PR61).\n\nStrengths and limitations of this studyO_LIBroad phenotypic assessment of healthy ageing across multiple health domains\nC_LIO_LIAdvanced analytic techniques (i.e. Latent Class Analysis regression) allows new insights\nC_LIO_LIA uniquely large neuroimaging sample combined with Bayesian inference allows for quantification of evidence for the null hypothesis\nC_LIO_LISubjective sleep measures may have drawbacks in older samples\nC_LIO_LICross-sectional data precludes modelling of within subject changes\nC_LI

Neuroscience↗

bioRxiv2016

DNA methylation adjusts the specificity of memories depending on the learning context and promotes relearning

The activity of the epigenetic writers DNA methyltransferases (Dnmts) after olfactory reward conditioning is important for both stimulus-specific long-term memory (LTM) formation and extinction. It, however, remains unknown which components of memory formation Dnmts regulate (e.g. associative vs. non-associative) and in what context (e.g. varying training conditions). Here we address these aspects in order to clarify the role of Dnmt-mediated DNA methylation in memory formation. We used a pharmacological Dnmt inhibitor and classical appetitive conditioning in the honeybee Apis mellifera, a well characterized model for classical conditioning. We quantified the effect of DNA methylation on naive odour and sugar responses, and on responses following olfactory reward conditioning. We show that (1) Dnmts do not influence naive odour or sugar responses, (2) Dnmts do not affect the learning of new stimuli, but (3) Dnmts influence odour-coding, i.e. 'correct' (stimulus-specific) LTM formation. Particularly, Dnmts reduce memory specificity when experience is low (one-trial training), and increase memory specificity when experience is high (multiple-trial training), generating an ecologically more useful response to learning. (4) In reversal learning conditions, Dnmts are involved in regulating both excitatory (re-acquisition) and inhibitory (forgetting) processes.

Neuroscience↗

bioRxiv2016

Natural DEET substitutes that are strong olfactory repellents of mosquitoes and flies

Despite shortcomings, N,N-Diethyl-3-methylbenzamide (DEET) has remained the gold-standard of insect repellents for >60 years. There are significant impediments to finding improved substitutes because the molecular targets causing repellency are unclear, new chemistries will require significant human-safety testing, and predicted costs for development are exorbitant. Here we identify shared structural features important for repellency and using a supervised chemical-informatics method screen insilico >400,000 compounds to identify >100 natural compounds as candidate repellents. We select 4 candidates that are affordable, 3 approved as safe for human food use, and demonstrate that they are strong olfactory and gustatory repellents to both mosquitoes and Drosophila. The chemicals do not dissolve plastic and have a mild and pleasant odor. These repellents are representative of a new generation of affordable substitutes for DEET that can be rapidly deployed globally because of excellent human-safety profiles, and have great potential in reducing deadly diseases by reducing mosquito-human contact.

Neuroscience↗

bioRxiv2016

Suboptimality in perception

LONG ABSTRACTHuman perceptual decisions are often described as optimal. This view reflects recent successes of Bayesian approaches to both cognition and perception. However, claims regarding optimality have been strongly criticized for their excessive flexibility and lack of explanatory power. Rebuttals from Bayesian theorists in turn claim that critics unfairly pick on select few papers. To resolve the issue regarding the role of optimality in perceptual decision making, we review the vast literature on suboptimal performance in perceptual tasks. Specifically, we discuss eight different classes of suboptimal perceptual decisions, including improper placement, maintenance, and adjustment of perceptual criteria, inadequate tradeoff between speed and accuracy, inappropriate confidence ratings, misweightings in cue combination, and findings related to various perceptual illusions and biases. We then extract the proposed explanations for the suboptimal behavior seen in each type of task. Critically, we show that these explanations naturally fit within an overarching Bayesian framework. Specifically, each suboptimality can be explained by alternative likelihood functions, priors, cost functions, or decision rules (LPCDs). We argue that unless the observers likelihood functions, priors, and cost functions are known, statements about the optimality or suboptimality of decision rules are meaningless. Further, the very definition of optimal behavior is debatable and may ultimately require appeals to evolutionary history beyond the current scope of perceptual science. The field should therefore shift its focus away from optimality. We propose a \"LPCD approach\" to perceptual decision making that focuses exclusively on uncovering the LPCD components, without debating whether the uncovered LPCDs are \"optimal\" or not.\n\nSHORT ABSTRACTHuman perceptual decisions are often described as optimal, but this view remains controversial. To resolve the issue, we review the vast literature on suboptimalities in perceptual tasks. We then extract the proposed explanations for the suboptimal behavior seen in each type of task and show that each suboptimality can be explained by alternative likelihood functions, priors, cost functions, or decision rules (LPCDs). We argue that general statements about the optimality or suboptimality of perceptual decisions are meaningless and propose a \"LPCD approach\" to perceptual decision making that focuses on the LPCD components rather than optimality.

Neuroscience↗

bioRxiv2016

Dissociation of reinforcement and Hebbian learning induces covert acquisition of value in the basal ganglia

This paper introduces a new hypothesis concerning the dissociated role of the basal ganglia in the selection and the evaluation of action that has been formulated using a theoretical model and confirmed experimentally in monkeys. To do so, prior to learning, we inactivated the internal part of the Globus Pallidus (GPi, the main output structure of the BG) with injections of muscimol and we tested monkeys on a variant of a two-armed bandit task where two stimuli are associated with two distinct reward probabilities (0.25 and 0.75 respectively). Unsurprisingly, performance in such condition are at the chance level because the output of basal ganglia is suppressed and they cannot influence behaviour. However, the theoretical model predicts that in the meantime, values of the stimuli are nonetheless covertly evaluated and learned. This has been tested and confirmed on the next day, when muscimol has been replaced by a saline solution: monkeys instantly showed significantly improved performances (above chance level), hence demonstrating they have covertly learned the relative value of the two stimuli. This tends to suggest a competition takes place in the Cortex-BG loop between two actors, one of whom being sensitive to criticism and the other not. Ultimately, the actual choice is valuated, independently of the origin of the decision.

Neuroscience↗

bioRxiv2016

Homozygous loss of autism-risk gene CNTNAP2 results in reduced local and long-range prefrontal functional connectivity

Functional connectivity aberrancies, as measured with resting-state fMRI (rsfMRI), have been consistently observed in the brain of autism spectrum disorders (ASD) patients. However, the genetic and neurobiological underpinnings of these findings remain unclear. Homozygous mutations in Contactin Associated Protein-like 2 (CNTNAP2), a neurexin-related cell-adhesion protein, are strongly linked to autism and epilepsy. Here we used rsfMRI to show that homozygous mice lacking Cntnap2 exhibit reduced long-range and local functional connectivity in prefrontal and midline brain \"connectivity hubs\". Long-range rsfMRI connectivity impairments affected heteromodal cortical regions and were prominent between fronto-posterior components of the mouse default-mode network (DMN), an effect that was associated with reduced social investigation, a core \"autism trait\" in mice. Notably, viral tracing revealed reduced frequency of prefrontal-projecting neural clusters in the cingulate cortex of Cntnap2-/- mutants, suggesting a possible contribution of defective mesoscale axonal wiring to the observed functional impairments. Macroscale cortico-cortical white matter organization appeared to be otherwise preserved in these animals. These findings reveal a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.

Neuroscience↗

bioRxiv2016

Gamma-rhythmic Gain Modulation

Cognition requires the dynamic modulation of effective connectivity, i.e. the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backwards to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation.

Neuroscience↗