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 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 2019Associations between vascular risk factors and brain MRI indices in UK Biobank Supplementary Material, bioRxiv, 2019-01-04
Aims Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macro- and microstructure in large community-dwelling populations across middle- and older age. Methods and Results Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholersterolaemia, BMI, and waist-hip ratio) and both global and regional brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-77 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤ 1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker. Conclusion Higher levels of VRFs were associated with poorer brain health across grey and white matter macro- and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasise the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.
biorxiv neuroscience 0-100-users 2019Fundamental bounds on learning performance in neural circuits, bioRxiv, 2019-01-01
How does the size of a neural circuit influence its learning performance? Intuitively, we expect the learning capacity of a neural circuit to grow with the number of neurons and synapses. Larger brains tend to be found in species with higher cognitive function and learning ability. Similarly, adding connections and units to artificial neural networks can allow them to solve more complex tasks. However, we show that in a biologically relevant setting where synapses introduce an unavoidable amount of noise, there is an optimal size of network for a given task. Beneath this optimal size, our analysis shows how adding apparently redundant neurons and connections can make tasks more learnable. Therefore large neural circuits can either devote connectivity to generating complex behaviors, or exploit this connectivity to achieve faster and more precise learning of simpler behaviors. Above the optimal network size, the addition of neurons and synaptic connections starts to impede learning performance. This suggests that overall brain size may be constrained by the need to learn efficiently with unreliable synapses, and may explain why some neurological learning deficits are associated with hyperconnectivity. Our analysis is independent of specific learning rules and uncovers fundamental relationships between learning rate, task performance, network size and intrinsic noise in neural circuits.
biorxiv neuroscience 0-100-users 2019Inception in visual cortex in vivo-silico loops reveal most exciting images, bioRxiv, 2018-12-29
Much of our knowledge about sensory processing in the brain is based on quasi-linear models and the stimuli that optimally drive them. However, sensory information processing is nonlinear, even in primary sensory areas, and optimizing sensory input is difficult due to the high-dimensional input space. We developed inception loops, a closed-loop experimental paradigm that combines in vivo recordings with in silico nonlinear response modeling to identify the Most Exciting Images (MEIs) for neurons in mouse V1. When presented back to the brain, MEIs indeed drove their target cells significantly better than the best stimuli identified by linear models. The MEIs exhibited complex spatial features that deviated from the textbook ideal of V1 as a bank of Gabor filters. Inception loops represent a widely applicable new approach to dissect the neural mechanisms of sensation.
biorxiv neuroscience 0-100-users 2018The mutational landscape of normal human endometrial epithelium, bioRxiv, 2018-12-24
All normal somatic cells are thought to acquire mutations. However, characterisation of the patterns and consequences of somatic mutation in normal tissues is limited. Uterine endometrium is a dynamic tissue that undergoes cyclical shedding and reconstitution and is lined by a gland-forming epithelium. Whole genome sequencing of normal endometrial glands showed that most are clonal cell populations derived from a recent common ancestor with mutation burdens differing from other normal cell types and manyfold lower than endometrial cancers. Mutational signatures found ubiquitously account for most mutations. Many, in some women potentially all, endometrial glands are colonised by cell clones carrying driver mutations in cancer genes, often with multiple drivers. Total and driver mutation burdens increase with age but are also influenced by other factors including body mass index and parity. Clones with drivers often originate during early decades of life. The somatic mutational landscapes of normal cells differ between cell types and are revealing the procession of neoplastic change leading to cancer.
biorxiv cancer-biology 0-100-users 2018