The population dynamics of a canonical cognitive circuit Supplementary Information, bioRxiv, 2019-01-10
The brain constructs distributed representations of key low-dimensional variables. These variables may be external stimuli or internal constructs of quantities relevant for survival, such as a sense of one's location in the world. We consider that the high-dimensional population-level activity vectors are the fundamental representational currency of a neural circuit, and these vectors trace out a low-dimensional manifold whose dimension and topology matches those of the represented variable. This manifold perspective -- applied to the mammalian head direction circuit across rich waking behaviors and sleep -- enables powerful inferences about circuit representation and mechanism, including Direct visualization and blind discovery that the network represents a one-dimensional circular variable across waking and REM sleep; fully unsupervised decoding of the coded variable; stability and attractor dynamics in the representation; the discovery of new dynamical trajectories during sleep; the limiting role of external rather than internal noise in the fidelity of memory states; and the conclusion that the circuit is set up to integrate velocity inputs according to classical continuous attractor models.
biorxiv neuroscience 0-100-users 2019False-positive neuroimaging Undisclosed flexibility in testing spatial hypotheses allows presenting anything as a replicated finding, bioRxiv, 2019-01-09
AbstractHypothesis testing in neuroimaging studies relies heavily on treating named anatomical regions (e.g., “the amygdala”) as unitary entities. Though data collection and analyses are conducted at the voxel level, inferences are often based on anatomical regions. The discrepancy between the unit of analysis and the unit of inference leads to ambiguity and flexibility in analyses that can create a false sense of reproducibility. For example, hypothesizing effects on “amygdala activity” does not provide a falsifiable and reproducible definition of precisely which voxels or which patterns of activation should be observed. Rather, it comprises a large number of unspecified sub-hypotheses, leaving room for flexible interpretation of findings, which we refer to as “model degrees of freedom.” From a survey of 135 functional Magnetic Resonance Imaging studies in which researchers claimed replications of previous findings, we found that 42.2% of the studies did not report any quantitative evidence for replication such as activation peaks. Only 14.1% of the papers used exact coordinate-based or a priori pattern-based models. Of the studies that reported peak information, 42.9% of the ‘replicated’ findings had peak coordinates more than 15 mm away from the ‘original’ findings, suggesting that different brain locations were activated, even when studies claimed to replicate prior results. To reduce the flexible and qualitative region-level tests in neuroimaging studies, we recommend adopting quantitative spatial models and tests to assess the spatial reproducibility of findings. Techniques reviewed here include permutation tests on peak distance, Bayesian MANOVA, and a priori multivariate pattern-based models. These practices will help researchers to establish precise and falsifiable spatial hypotheses, promoting a cumulative science of neuroimaging.
biorxiv neuroscience 200-500-users 2019From Habitat Use to Social Behavior Natural History of a Voiceless Poison Frog, Dendrobates tinctorius, bioRxiv, 2019-01-09
Descriptive studies of natural history have always been a source of knowledge on which experimental work and scientific progress rely. Poison frogs are a well-studied group of small Neotropical frogs with diverse parental behaviors, distinct calls, and bright colors that warn predators about their toxicity; and a showcase of advances in fundamental biology through natural history observations. The dyeing poison frog, Dendrobates tinctorius, is emblematic of the Guianas region, widespread in the pet-trade, and increasingly popular in research. This species shows several unusual behaviors, such as the lack of advertisement calls and the aggregation around tree-fall gaps, which remain poorly described and understood. Here, we summarize our observations from a natural population of D. tinctorius in French Guiana collected over various field trips between 2009 and 2017; our aim is to provide groundwork for future fundamental and applied research spanning parental care, animal dispersal, disease spread, habitat use in relation to color patterns, and intra specific communication, to name a few. We report sex differences in habitat use and the striking invasion of tree-fall gaps; describe their courtship and aggressive behaviors; document egg development and tadpole transport; and discuss how the knowledge generated by this study could set the grounds for further research on the behavior, ecology, and conservation of this species.
biorxiv animal-behavior-and-cognition 0-100-users 2019Multiplexed electron microscopy by fluorescent barcoding allows screening for ultrastructural phenotype, bioRxiv, 2019-01-09
Genetic screens performed using high-throughput fluorescent microscopes have generated large datasets that have contributed many insights into cell biology. However, such approaches typically cannot tackle questions requiring knowledge of ultrastructure below the resolution limit of fluorescent microscopy. Electron microscopy (EM) is not subject to this resolution limit, generating detailed images of cellular ultrastructure, but requires time consuming preparation of individual samples, limiting its throughput. Here we overcome this obstacle and describe a robust method for screening by high-throughput electron microscopy. Our approach uses combinations of fluorophores as barcodes to mark the genotype of each cell in mixed populations, and correlative light and electron microscopy to read the fluorescent barcode of each cell before it is imaged by electron microscopy. Coupled with an easy-to-use software workflow for correlation, segmentation and computer image analysis, our method allows to extract and analyze multiple cell populations from each EM sample preparation. We demonstrate the method on several organelles with samples that each contain up to 15 different yeast variants. The methodology is not restricted to yeast, can be scaled to higher-throughput, and can be utilized in multiple ways to enable electron microscopy to become a powerful screening methodology.
biorxiv cell-biology 100-200-users 2019Optical clearing of living brains with MAGICAL to extend in vivo imaging, bioRxiv, 2019-01-09
To understand brain functions, it is important to observe directly how multiple neural circuits are performing in living brains. However, due to tissue opaqueness, observable depth and spatiotemporal resolution are severely degraded in vivo. Here, we propose an optical brain clearing method for in vivo fluorescence microscopy, termed MAGICAL (Magical Additive Glycerol Improves Clear Alive Luminance). MAGICAL enabled two-photon microscopy to capture vivid images with fast speed, at cortical layer V and hippocampal CA1 in vivo. Moreover, MAGICAL promoted conventional confocal microscopy to visualize finer neuronal structures including synaptic boutons and spines in unprecedented deep regions, without intensive illumination leading to phototoxic effects. Fluorescence Emission Spectrum Transmissive Analysis (FESTA) showed that MAGICAL improved in vivo transmittance of shorter wavelength light, which is vulnerable to optical scattering thus unsuited for in vivo microscopy. These results suggest that MAGICAL would transparentize living brains via scattering reduction.
biorxiv neuroscience 200-500-users 2019Perception of naturally dead conspecifics impairs health and longevity through serotonin signaling in Drosophila, bioRxiv, 2019-01-09
Sensory perception modulates health and aging across taxa. Understanding the nature of relevant cues and the mechanisms underlying their action may lead to novel interventions that improve the length and quality of life. In humans, psychological trauma is often associated with the recognition of dead individuals, with chronic exposure leading to persistent mental health issues including depression and post-traumatic stress disorder. The mechanisms that link mental and physical health, and the degree to which these are shared across species, remain largely unknown. Here we show that the vinegar fly, Drosophila melanogaster, has the capability to perceive dead conspecifics in its environment and that this perceptive experience induces both short- and long-term effects on health and longevity. Death perception is mediated by visual and olfactory cues, and remarkably, its effects on aging are eliminated by targeted attenuation of serotonin signaling. Our results suggest a complex perceptive ability in Drosophila that reveals deeply conserved mechanistic links between psychological state and aging, the roots of which might be unearthed using invertebrate model systems.
biorxiv animal-behavior-and-cognition 100-200-users 2019