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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.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 451 records · Page 25Linked to original sources

bioRxiv2014

The invariance hypothesis implies domain-specific regions in visual cortex

Is visual cortex made up of general-purpose information processing machinery, or does it consist of a collection of specialized modules? If prior knowledge, acquired from learning a set of objects is only transferable to new objects that share properties with the old, then the recognition systems optimal organization must be one containing specialized modules for different object classes. Our analysis starts from a premise we call the invariance hypothesis: that the computational goal of the ventral stream is to compute an invariant-to-transformations and discriminative signature for recognition. The key condition enabling approximate transfer of invariance without sacrificing discriminability turns out to be that the learned and novel objects transform similarly. This implies that the optimal recognition system must contain subsystems trained only with data from similarly-transforming objects and suggests a novel interpretation of domain-specific regions like the fusiform face area (FFA). Furthermore, we can define an index of transformation-compatibility, computable from videos, that can be combined with information about the statistics of natural vision to yield predictions for which object categories ought to have domain-specific regions in agreement with the available data. The result is a unifying account linking the large literature on view-based recognition with the wealth of experimental evidence concerning domain-specific regions.

Neuroscience↗

bioRxiv2014

Functional knockout of forebrain protein 14-3-3 disrupts conditioned taste aversion learning

Protein 14-3-3 isoforms are key to many cellular processes and are ubiquitous throughout the brain. 14-3-3 is a regulator of ser/thr phospho-signaling by binding and sequestering phosphorylated substrates including kinases, histone deactylases, and transcription factors. The role of protein 14-3-3 in conditioned taste aversion learning (CTA) has not previously been examined. We parameterized CTA learning in difopein- YFP transgenic mice, which have widespread by expression of the artificial peptide difopein in the forebrain, including the basolateral amygdala and insular cortex, resulting in functional knock-out (FKO) of all 14-3-3 isoforms . We found that a single pairing of saccharin or NaCl (CS) and LiCl injection (US) was not sufficient to induce CTA in FKO mice. Multiples pairings of CS and US did lead to CTA acquisition in the FKO mice; however, the CTA rapidly extinguished within 30 minutes to 24 hours after acquisition. Additionally, we found that 14-3-3 FKO mice have an attenuated visceral neuraxis response to LiCl as measured by c-Fos induction. The deficit in FKO was not due to an inability to discriminate or avoid tastants, because they showed normal unconditioned taste preferences for both palatable (saccharin, maltodextrin , low concentration NaCl) and unpalatable tastants (quinine, HCl, and high concentration NaCl) and they were able to reduce intake of a maltodextrin solution adulterated with quinine. The FKO did not have a global deficit in ingestive learning, because they were able to form a conditioned flavor-nutrient preference. Thus, FKO of forebrain 14-3-3 appears to disrupt CTA learning leading to forgetting, rapid extinction, or failure to reconsolidate. This further implicates ser/thr phospho-signaling pathways in the regulation of long-term CTA learning.

Neuroscience↗

bioRxiv2014

Pre-trial exogenous visual flicker does not affect behavioral or EEG signatures of conflict processing

Activity in the theta frequency band (4-8 Hz) over medial prefrontal regions has been consistently implicated in top-down cognitive control processes, including recognizing and resolving response conflict. It remains an unanswered question whether these theta-band dynamics are a neural mechanism of cognitive control, or instead are epiphenomenal to the neural computational machinery but are useful indices of brain function. Here we addressed this question by attempting to boost conflict processing (or its EEG theta-band signatures) via pre-trial exogenous theta-band visual flicker. Although the flicker successfully entrained posterior brain networks, there were no effects of flicker on behavior or on EEG signatures of conflict processing. In this paper, we detail our attempts and discuss possible future directions for using exogenous flicker in the study of the role of endogenous brain oscillations in conflict processing.

Neuroscience↗

bioRxiv2014

Visual areas exert feedforward and feedback influences through distinct frequency channels

Visual cortical areas are thought to form a hierarchy and to subserve cognitive functions by interacting in both feedforward and feedback directions. While feedforward influences convey sensory signals, feedback influences modulate brain responses to a given sensory stimulus according to the current behavioural context. Many studies have demonstrated effects of feedback influences on feedforward driven responses and on behaviour. Also, anatomical projections in both directions have been identified. However, although these studies have revealed the anatomical paths and the neurophysiological consequences of influences in both directions, the neurophysiological mechanisms through which these influences are exerted remain largely elusive. Here we show that in the primate visual system, feedforward influences are carried by theta-band (~4 Hz) and gamma-band (~60-80 Hz) synchronization, and feedback influences by beta-band (~14-18 Hz) synchronization. These frequency-specific asymmetries in directed influences were revealed by simultaneous local field potential recordings from eight visual areas and an analysis of Granger-causal influences across all 28 pairs of areas. The asymmetries in directed influences correlated directly with asymmetries in anatomy and enabled us to build a visual cortical hierarchy from the influence asymmetries alone. Across different task periods, most areas stayed at their hierarchical position, whereas particularly frontal areas moved dynamically. Our results demonstrate that feedforward and feedback signalling use different frequency channels, which might subserve their differential communication requirements and lead to differential local consequences. The possibility to infer hierarchical relationships through functional data alone might make it possible to derive a cortical hierarchy in the living human brain.

Neuroscience↗

bioRxiv2014

Missing kinaesthesia challenges precise naturalistic cortical prosthetic control

A major assumption of brain-machine interface (BMI) research is that patients with disconnected neural pathways can still volitionally recall precise motor commands that could be decoded for naturalistic prosthetic control. However, the disconnected condition of these patients also blocks kinaesthetic feedback from the periphery, which has been shown to regulate centrally generated output responsible for accurate motor control. Here we tested how well motor commands are generated in the absence of kinaesthetic feedback by decoding hand movements from human scalp electroencephalography (EEG) in three conditions: unimpaired movement, imagined movement, and movement attempted during temporary disconnection of peripheral afferent and efferent nerves by ischemic nerve block. Our results suggest that the recall of cortical motor commands is impoverished in absence of kinaesthetic feedback, challenging the possibility of precise naturalistic cortical prosthetic control.

Neuroscience↗

bioRxiv2014

Independent Theta Phase Coding Accounts for CA1 Population Sequences and Enables Flexible Remapping

Populations of hippocampal place cells encode an animals past, current and future location through sequences of action potentials generated within each cycle of the network theta rhythm. These sequential representations have been suggested to result from temporally coordinated synaptic interactions within and between cell assemblies. In contrast, we show that a model based on rate and phase coding in independent neurons is sufficient to explain the organization of CA1 population activity during theta states. We show that CA1 population activity can be described as an evolving traveling wave that exhibits phase coding, rate coding, spike sequences and that generates an emergent population theta rhythm. We identify measures of global remapping and intracellular theta dynamics as critical for distinguishing mechanisms for pacemaking and coordination of sequential population activity. Our analysis suggests that independent coding enables flexible generation of sequential population activity within the duration of a single theta cycle.

Neuroscience↗

bioRxiv2014

Collecting reward to defend homeostasis: A homeostatic reinforcement learning theory

Efficient regulation of internal homeostasis and defending it against perturbations requires complex behavioral strategies. However, the computational principles mediating brains homeostatic regulation of reward and associative learning remain undefined. Here we use a definition of primary rewards, as outcomes fulfilling physiological needs, to build a normative theory showing how learning motivated behavior is modulated by the internal state of the animal. The theory proves that seeking rewards is equivalent to the fundamental objective of physiological stability, defining the notion of physiological rationality of behavior. We further give a formal basis for temporal discounting of reward. It also explains how animals learn to act predictively to preclude prospective homeostatic challenges, and attributes a normative computational role to the modulation of midbrain dopaminergic activity by hypothalamic signals.

Neuroscience↗

bioRxiv2014

Ultra fast tissue staining with chemical tags

Genetically encoded fluorescent proteins and immunostainings are widely used to detect cellular or sub-cellular structures in thick biological samples. However, each approach suffers from limitations, including low signal and limited spectral flexibility or slow speed, poor penetration and high background, respectively. Here we overcome these limitations by using transgenically expressed chemical tags for rapid, even and low-background labeling of thick biological tissues. We construct a platform of widely applicable transgenic Drosophila reporter lines, demonstrating that chemical labeling can accelerate staining of whole-mount fly brains by a factor of 100x. Together, this tag-based approach drastically improves the speed and specificity of labeling genetically marked cells in intact and/or thick biological samples.

Neuroscience↗

bioRxiv2014

Practopoiesis: Or how life fosters a mind

The mind is a biological phenomenon. Thus, biological principles of organization should also be the principles underlying mental operations. Practopoiesis states that the key for achieving intelligence through adaptation is an arrangement in which mechanisms laying a lower level of organization, by their operations and interaction with the environment, enable creation of mechanisms lying at a higher level of organization. When such an organizational advance of a system occurs, it is called a traverse. A case of traverse is when plasticity mechanisms (at a lower level of organization), by their operations, create a neural network anatomy (at a higher level of organization). Another case is the actual production of behavior by that network, whereby the mechanisms of neuronal activity operate to create motor actions. Practopoietic theory explains why the adaptability of a system increases with each increase in the number of traverses. With a larger number of traverses, a system can be relatively small and yet, produce a higher degree of adaptive/intelligent behavior than a system with a lower number of traverses. The present analyses indicate that the two well-known traverses--neural plasticity and neural activity--are not sufficient to explain human mental capabilities. At least one additional traverse is needed, which is named anapoiesis for its contribution in reconstructing knowledge e.g., from long-term memory into working memory. The conclusions bear implications for brain theory, the mind-body explanatory gap, and developments of artificial intelligence technologies.

Neuroscience↗

bioRxiv2014

Inhibition of protein translation by the DISC1-Boymaw fusion gene from a Scottish family with major psychiatric disorders

The t(1; 11) translocation appears to be the causal genetic lesion with 70% penetrance for schizophrenia, major depression, and other psychiatric disorders in a Scottish family. Molecular studies identified the disruption of the DISC1 (disrupted-in-schizophrenia 1) gene by chromosome translocation at chromosome 1q42. Our previous studies, however, revealed that the translocation also disrupted another gene, Boymaw (also termed DISC1FP1), on chromosome 11. After translocation, two fusion genes (the DISC1-Boymaw (DB7) and the Boymaw-DISC1 (BD13)) are generated between the DISC1 and Boymaw genes. In the present study, we report that expression of the DB7 fusion gene inhibits both intracellular NADH oxidoreductase activities and protein translation. We generated humanized DISC1-Boymaw mice with gene targeting to examine the in vivo functions of the fusion genes. Consistent with the in vitro studies on the DB7 fusion gene, protein translation activity is decreased in the hippocampus and in cultured primary neurons from the brains of the humanized mice. Expression of Gad67, Nmdar1, and Psd95 proteins are also reduced. The humanized mice display prolonged and increased responses to the NMDA receptor antagonist, ketamine, on various mouse genetic backgrounds. Abnormal information processing of acoustic startle and depressive-like behaviors are also observed. In addition, the humanized mice display abnormal erythropoiesis, which was reported to associate with depression in humans. Expression of the DB7 fusion gene may reduce protein translation to impair brain functions and thereby contribute to the pathogenesis of major psychiatric disorders.

Neuroscience↗

bioRxiv2014

Boymaw, Overexpressed in Brains with Major Psychiatric Disorders, May Encode a Small Protein to Inhibit Mitochondrial Function and Protein Translation

The t(1,11) chromosome translocation co-segregates with major psychiatric disorders in a large Scottish family. The translocation disrupts the DISC1 and Boymaw (DISC1FP1) genes on chromosomes 1 and 11, respectively. After translocation, two fusion genes are generated. Our recent studies found that the DISC1-Boymaw fusion protein is localized in mitochondria and inhibits oxidoreductase activity, rRNA expression, and protein translation. Mice carrying the DISC1-Boymaw fusion genes display intermediate behavioral phenotypes related to major psychiatric disorders. Here, we report that the Boymaw gene encodes a small protein predominantly localized in mitochondria. The Boymaw protein inhibits oxidoreductase activity, rRNA expression, and protein translation in the same way as the DISC1-Boymaw fusion protein. Interestingly, Boymaw expression is up-regulated by different stressors at RNA and/or protein translational levels. In addition, we found that Boymaw RNA expression is significantly increased in the postmortem brains of patients with major psychiatric disorders. Our studies therefore suggest that the Boymaw gene is a potential susceptibility gene for major psychiatric disorders in both the Scottish t(1,11) family and the general population of patients.

Neuroscience↗

bioRxiv2014

Rapid transcriptional response to physiological neuronal activity in vivo revealed by transcriptome sequencing

Neuronal activity serves as a gateway between external stimulus from environment and the brain, often inducing gene expression changes. Alternative splicing (AS) is a widespread mechanism of increasing the number of transcripts produced from a single gene and has been shown to alter properties of neuronal genes, such as ion channels (Xie and Black 2001) and neurotransmitter receptors (Mu et al. 2003). Patterns of neural tissue-specific AS have been identified, often regulated by neuron-specific splicing factors that are essential for survival (Jensen et al. 2000; Li et al. 2007), demonstrating the importance of AS in neurons. In vitro studies of neuronal activity found AS changes in response to neuronal activity in addition to transcriptional ones, raising the question of whether such changes are recapitulated in vivo on behaviorally relevant timescales. We developed a paradigm for studying physiological neuronal activity through controlled stimulation of the olfactory bulb, and performed RNA-Seq transcriptome analysis of olfactory bulbs from odor-deprived and stimulated mice. We found that physiological stimulation induces large, rapid and reproducible changes in transcription in vivo, and that the activation of a core set of activity-regulated factors is recapitulated in an in vitro model of neuronal stimulation. However, physiological activity did not induce global changes in post-transcriptional mRNA processing, such as AS or alternative cleavage and polyadenylation. In contrast, analysis of RNA-Seq from in vitro stimulation models showed rapid activity-dependent changes in both transcription and mRNA processing. Our results provide the first genome-wide look at neuronal activity-dependent mRNA processing and suggest that rapid changes in AS might not be the dominant form of transcriptome alterations that take place during olfactory rodent behavior.

Neuroscience↗

bioRxiv2014

NBLAST: Rapid, sensitive comparison of neuronal structure and construction of neuron family databases

Neural circuit mapping is generating datasets of 10,000s of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches.\n\nWe validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and un-reported topographical features. Fully automated clustering organized the validation dataset into 1052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types including searching neurons against transgene expression patterns. Finally we show that NBLAST is effective with data from other invertebrates and zebrafish.

Neuroscience↗

bioRxiv2014

Combining genome-scale Drosophila 3D neuroanatomical data by bridging template brains

To analyse neuron data at scale, neuroscientists expend substantial effort reading documentation, installing dependencies and moving between analysis and visualisation environments. To facilitate this, we have developed a suite of interoperable open-source R packages called the natverse. The natverse allows users to read local and remote data, perform popular analyses including visualisation, clustering and graph-theoretic analysis of neuronal branching. Unlike most tools, the natverse enables comparison of morphology and connectivity across many neurons after imaging or co-registration within a common template space. The natverse also enables transformations between different template spaces and imaging modalities. We demonstrate tools that integrate the vast majority of Drosophila neuroanatomical light microscopy and electron microscopy connectomic datasets. The natverse is an easy-to-use environment for neuroscientists to solve complex, large-scale analysis challenges as well as an open platform to create new code and packages to share with the community.

Neuroscience↗

bioRxiv2014

Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum

Modification of spatial attention via reinforcement learning (Lee & Shomstein, 2013) requires the integration of reward, attention, and executive processes. Corticostriatal pathways are an ideal neural substrate for this integration because these projections exhibit a globally parallel (Alexander, De Long, and Strick, 1985), but locally overlapping (Haber, 2003), topographical organization. Here, we explored whether there are unique striatal regions that exhibit convergent anatomical connections from orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), and posterior parietal cortex. Deterministic fiber tractography on diffusion spectrum imaging data from neurologically healthy adults (N=60) was used to map fronto-and parieto-striatal projections. In general, projections from cortex were organized in a rostral-caudal gradient along the striatal nuclei; however, we also identified two bilateral convergence zones--one in the caudate nucleus and another in the putamen--that consisted of voxels with projections from OFC, DLPFC, and parietal regions. The distributed cortical connectivity of these striatal convergence zones was confirmed with follow-up functional connectivity analysis from resting state fMRI data from 55 of the participants, in which a high percentage (62-80%) of structurally connected voxels also showed significant functional connectivity. These results delineate a neurologically plausible network of converging corticostriatal projections that may support the integration of reward, executive control, and spatial attention that occurs during spatial reinforcement learning.

Neuroscience↗

bioRxiv2014

Detecting pairwise correlations in spike trains: an objective comparison of methods and application to the study of retinal waves.

Correlations in neuronal spike times are thought to be key to processing in many neural systems. Many measures have been proposed to summarise these correlations and of these the correlation index is widely used and is the standard in studies of spontaneous retinal activity. We show that this measure has two undesirable properties: it is unbounded above and confounded by firing rate. We list properties needed for a measure to fairly quantify and compare correlations and we propose a novel measure of correlation -- the Spike Time Tiling Coefficient. This coefficient, the correlation index and 33 other measures of correlation of spike times are blindly tested for the required properties on synthetic and experimental data. On the basis of this, we propose a measure (the Spike Time Tiling Coefficient) to replace the correlation index. To demonstrate the benefits of this measure, we re-analyse data from seven key studies which previously used the correlation index to investigate the nature of spontaneous activity. We re-analyse data from {beta}2(KO) and {beta}2(TG) mutants, mutants lacking connexin isoforms and also the age-dependent changes in wild type and {beta}2(KO) correlations. Re-analysis of the data using the proposed measure can significantly change the conclusions. It leads to better quantification of correlations and therefore better inference from the data. We hope that the proposed measure will have wide applications, and will help clarify the role of activity in retinotopic map formation.

Neuroscience↗

bioRxiv2014

Near-optimal decoding of transient stimuli from coupled neuronal subpopulations

Coupling between sensory neurons impacts their tuning properties and correlations in their responses. How such coupling affects sensory representations and ultimately behavior remains unclear. We investigated the role of neuronal coupling during visual processing using a realistic biophysical model of the vertical system (VS) cell network in the blow fly. These neurons are thought to encode the horizontal rotation axis during rapid free flight manoeuvres. Experimental findings suggest neurons of the vertical system are strongly electrically coupled, and that several downstream neurons driving motor responses to ego-rotation receive inputs primarily from a small subset of VS cells. These downstream neurons must decode information about the axis of rotation from a partial readout of the VS population response. To investigate the role of coupling, we simulated the VS response to a variety of rotating visual scenes and computed optimal Bayesian estimates from the relevant subset of VS cells. Our analysis shows that coupling leads to near-optimal estimates from a subpopulation readout. In contrast, coupling between VS cells has no impact on the quality of encoding in the response of the full population. We conclude that coupling at one level of the fly visual system allows for near-optimal decoding from partial information at the subsequent, pre-motor level. Thus, electrical coupling may provide a general mechanism to achieve near-optimal information transfer from neuronal subpopulations across organisms and modalities.

Neuroscience↗

bioRxiv2014

Statistical mechanics of multistable perception

The stochastic dynamics of multistable perception poses an enduring challenge to our understanding of neural signal processing in the brain. We show that the emergence of perception switching and stability can be understood using principles of probabilistic Bayesian inference where the prior temporal expectations are matched to a scale-free power spectrum, characteristic of fluctuations in the natural environment. The optimal percept dynamics are inferred by an exact mapping of the statistical estimation problem to the motion of a dissipative quantum particle in a multi-well potential. In the bistable case the problem is further mapped to a long-ranged Ising model. Optimal inference in the presence of a 1/f noise prior leads to critical dynamics, exhibiting a dynamical phase transition from unstable perception to stable perception, as demonstrated in recent experiments. The effect of stimulus fluctuations and perception bias is also discussed.

Neuroscience↗