SEARCH · bioRxiv Science

Results for “Neuroscience”

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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources

bioRxiv2016

Video-rate volumetric functional imaging of the brain at synaptic resolution

Neurons and neural networks often extend hundreds to thousands of micrometers in three dimensions. To capture all the calcium transients associated with their activity, we need volume imaging methods with sub-second temporal resolution. Such speed is challenging for conventional two-photon laser scanning microscopy (2PLSM) to achieve, because of its dependence on serial focal scanning in 3D and the limited brightness of indicators. Here we present an optical module that can be easily integrated into standard 2PLSMs to generate an axially elongated Bessel focus. Scanning the Bessel focus in 2D turned frame rate into volume rate and enabled video-rate volumetric imaging. Using Bessel foci designed to maintain synaptic-level lateral resolution in vivo, we demonstrated the power of this approach in enabling discoveries for neurobiology by imaging the calcium dynamics of volumes of neurons and synapses in fruit flies, zebrafish larvae, mice, and ferrets in vivo.

Neuroscience↗

bioRxiv2016

Familiarity Facilitates Feature-based Face Processing

Recognition of personally familiar faces is remarkably efficient, effortless and robust. We asked if feature-based face processing facilitates detection of familiar faces by testing the effect of face inversion on a visual search task for familiar and unfamiliar faces. Because face inversion disrupts configural and holistic face processing, we hypothesized that inversion would diminish the familiarity advantage to the extent that it is mediated by such processing. Subjects detected personally familiar and stranger target faces in arrays of two, four, or six face images. Subjects showed significant facilitation of personally familiar face detection for both upright and inverted faces. The effect of familiarity on target absent trials, which involved only rejection of unfamiliar face distractors, suggests that familiarity facilitates rejection of unfamiliar distractors as well as detection of familiar targets. The preserved familiarity effect for inverted faces suggests that facilitation of face detection afforded by familiarity reflects mostly feature-based processes.

Neuroscience↗

bioRxiv2016

ICGenealogy: Mapping the function of neuronal ion channels in model and experiment

Ion channel models are the building blocks of computational neuron models. Their biological fidelity is therefore crucial for the interpretability of simulations. However, the number of published models, and the lack of standardization, make the comparison of models with one another and with experimental data difficult. Here, we present a framework for the automated large-scale classification of ion channel models. Using annotated metadata and model responses to a set of voltage-clamp protocols, we assigned 2378 models of voltage- and calcium-gated ion channels coded in NEURON to 211 clusters. The IonChannelGenealogy web interface provides an interactive resource for the categorization of new and existing models and experimental recordings. It enables quantitative comparisons of simulated and/or measured ion channel kinetics, and facilitates field-wide standardization of experimentally-constrained modeling.

Neuroscience↗

bioRxiv2016

Task-specific shaping of feature-based attention in area MT

Non-spatial selective attention is based on the notion that specific features or objects in the visual environment are effectively prioritized in cortical visual processing. Feature-based attention (FBA) in particular, is a well-studied process that dynamically and selectively enhances neurons preferentially processing the attended feature attribute (e.g. leftward motion). In everyday life, however, behavior may require high sensitivity for an entire feature dimension (e.g. motion). Yet, evidence for feature dimension-specific attentional modulation on a cellular level is lacking. We here investigate neuronal activity in macaque motion-selective medio-temporal area (MT) in an experimental setting requiring the monkeys to detect either a motion change or a color change. We hypothesized that neural activity in MT is enhanced if the task requires perceptual sensitivity to motion. Despite identical visual stimulation, we found that mean firing rates were higher in the motion task, and response variability and latency were lower as compared to the color task. This task-specific response modulation in the processing of visual motion was independent from the relation between attended and stimulating motion direction. It emerged already in the absence of visual input, and consisted of a spatially global and tuning-independent shift of the MT baseline activity. The results provide single cell support for the hypothesis of a feature dimension-specific top-down signal emphasizing the processing of an entire feature class.

Neuroscience↗

bioRxiv2016

Local and thalamic origins of ongoing and sensory evoked cortical correlations

Thalamic inputs of layer 4 (L4) cells in sensory cortices are outnumbered by local connections. Thus, it was suggested that robust sensory response in L4 emerges due to synchronized thalamic activity. In order to investigate the role of both inputs in generation of cortical synchronization, we isolated the thalamic excitatory inputs of cortical cells by optogenetically silencing cortical firing. In anesthetized mice, we measured the correlation between isolated thalamic synaptic inputs of simultaneously patched nearby L4 cells of the barrel cortex. In contrast to correlated activity of excitatory synaptic inputs in the intact cortex, isolated thalamic inputs exhibit lower variability and asynchronous spontaneous and sensory evoked inputs. These results were further supported in awake mice when we recorded the excitatory inputs of individual cortical cells simultaneously with the local field potential (LFP) in a nearby site. Our results therefore indicate that cortical synchronization emerges by intracortical coupling.

Neuroscience↗

bioRxiv2016

Intrinsic functional architecture of the macaque dorsal and ventral lateral frontal cortex

Investigations of the cellular and connectional organization of the lateral frontal cortex (LFC) of the macaque monkey provide indispensable knowledge for generating hypotheses about the human LFC. However, despite numerous investigations, there are still debates on the organization of this brain region. In vivo neuroimaging techniques such as resting-state fMRI can be used to define the functional circuitry of brain areas producing results largely consistent with gold-standard invasive tract-tracing techniques and offering the opportunity for cross-species comparison within the same modality. Our results using resting-state fMRI from macaque monkeys to uncover the intrinsic functional architecture of the LFC corroborate previous findings and inform current debates. Specifically, we show that i) the region in the midline and anterior to the superior arcuate sulcus is divided in two areas separated by the posterior supraprincipal dimple; ii) the cytoarchitectonically defined area 6DC/F2 contains two connectional divisions; and, iii) a distinct area occupies the cortex around the spur of the arcuate, updating what was previously proposed to be the border between dorsal and ventral motor/premotor areas. Within the ventral LFC specifically, the derived parcellation clearly suggests the presence of distinct areas i) with a somatomotor/orofacial connectional signature (putative area 44), ii) with an occulomotor connectional signature (putative frontal eye fields), and iii) premotor areas possibly hosting laryngeal and arm representations. Our results illustrate in detail the intrinsic functional architecture of the macaque LFC, thus providing valuable evidence for debates on its organization.

Neuroscience↗

bioRxiv2016

A robust role for motor cortex

The role of motor cortex in non-primate mammals remains unclear. More than a century of stimulation, anatomical and electrophysiological studies has implicated neural activity in this region with all kinds of movement. However, following the removal of motor cortex, rats retain most of their adaptive behaviours, including previously learned skilled movements. Here we revisit these two conflicting views of motor cortex and present a new behaviour assay, challenging animals to respond to unexpected situations while navigating a dynamic obstacle course. Surprisingly, rats with motor cortical lesions show clear impairments facing an unexpected collapse of the obstacles, while showing no impairment with repeated trials in many motor and cognitive metrics of performance. We propose a new role for motor cortex: extending the robustness of sub-cortical movement systems, specifically to unexpected situations demanding rapid motor responses adapted to environmental context. The implications of this idea for current and future research are discussed.

Neuroscience↗

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↗