Search bioRxiv⌕ Search

Biology subjects

Liang, E.

Publications and source records attributed to Liang, E..

27 records · Page 2Linked to original sources

Differential encoding of temporal context and expectation under representational drift across hierarchically connected areas

The classic view that neural populations in sensory cortices preferentially encode responses to incoming stimuli has been strongly challenged by recent experimental studies. Despite the fact that a large fraction of variance of visual responses in rodents can be attributed to behavioral state and movements, trial-history, and salience, the effects of contextual modulations and expectations on sensory-evoked responses in visual and association areas remain elusive. Here, we present a comprehensive experimental and theoretical study showing that hierarchically connected visual and association areas differentially encode the temporal context and expectation of naturalistic visual stimuli, consistent with the theory of hierarchical predictive coding. We measured neural responses to expected and unexpected sequences of natural scenes in the primary visual cortex (V1), the posterior medial higher order visual area (PM), and retrosplenial cortex (RSP) using 2-photon imaging in behaving mice collected through the Allen Institute Mindscopes OpenScope program. We found that information about image identity in neural population activity depended on the temporal context of transitions preceding each scene, and decreased along the hierarchy. Furthermore, our analyses revealed that the conjunctive encoding of temporal context and image identity was modulated by expectations of sequential events. In V1 and PM, we found enhanced and specific responses to unexpected oddball images, signaling stimulus-specific expectation violation. In contrast, in RSP the population response to oddball presentation recapitulated the missing expected image rather than the oddball image. These differential responses along the hierarchy are consistent with classic theories of hierarchical predictive coding whereby higher areas encode predictions and lower areas encode deviations from expectation. We further found evidence for drift in visual responses on the timescale of minutes. Although activity drift was present in all areas, population responses in V1 and PM, but not in RSP, maintained stable encoding of visual information and representational geometry. Instead we found that RSP drift was independent of stimulus information, suggesting a role in generating an internal model of the environment in the temporal domain. Overall, our results establish temporal context and expectation as substantial encoding dimensions in the visual cortex subject to fast representational drift and suggest that hierarchically connected areas instantiate a predictive coding mechanism.

neuroscience↗

Multimodal, multiscale connectivity blueprints of the cerebral cortex

The brain is composed of disparate neural populations that communicate and interact with one another. Although fiber bundles, similarities in molecular architecture, and synchronized neural activity all represent brain connectivity, a comprehensive study of how all these connectivity modes jointly reflect brain structure and function remains missing. Here we systematically integrate seven multimodal, multiscale brain connectivity profiles derived from gene expression, neurotransmitter receptor density, cellular morphology, glucose metabolism, haemodynamic activity, and electrophysiology. We uncover a compact set of universal organizational principles through which brain geometry and neuroanatomy shape emergent connectivity modes. Connectivity modes also exhibit unique and diverse connection patterns, hub profiles, dominant gradients, and modular organization. Throughout, we observe a consistent primacy of molecular connectivity modes--namely correlated gene expression and receptor similarity--that map well onto multiple phenomena including the rich club and patterns of cortical abnormalities across 13 neurological, psychiatric, and neurodevelopmental disorders. Finally, we fuse all seven connectivity modes into a single multimodal network and show that it maps onto major organizational features of the brain including structural conenctivity, intrinsic functional networks, and cytoarchitectonic classes. Altogether, this work contributes to next-generation connectomics and the integrative study of inter-regional relationships.

neuroscience↗

Taxonomic classification methods reveal a new subgenus in the paramyxovirus subfamily Orthoparamyxovirinae

As part of a broad One Health surveillance effort to detect novel viruses in wildlife and people, we report several paramyxoviruses sequenced primarily from bats during 2013 and 2014 in Brazil and Malaysia, including seven from which we recovered full-length genomes. Of these, six represent the first full-length paramyxovirus genomes sequenced from the Americas, including two sequences which are the first full-length bat morbillivirus genomes published to date. Our findings add to the vast number of viral sequences in public repositories that have been increasing considerably in recent years due to the rising accessibility of metagenomics. Taxonomic classification of these sequences in the absence of phenotypic data has been a significant challenge, particularly in the paramyxovirus subfamily Orthoparamyxovirinae, where the rate of discovery of novel sequences has been substantial. Using pairwise amino acid sequence classification (PASC), we describe a novel genus within this subfamily tentatively named Jeishaanvirus, which we propose should include as subgenera Jeilongvirus, Shaanvirus, and a novel South American subgenus Cadivirus. We also highlight inconsistencies in the classification of Tupaia virus and Mojiang virus using the same demarcation criteria and show that members of the proposed subgenus Shaanvirus are paraphyletic. Importantly, this study underscores the critical importance of sequence length in PASC analysis as well as the importance of biological characteristics such as genome organization in the taxonomic classification of viral sequences.

microbiology↗

Metabolic and functional connectivity provide unique and complementary insights into cognition-connectome relationships

A major challenge in current cognitive neuroscience is how functional brain connectivity gives rise to human cognition. Functional magnetic resonance imaging (fMRI) describes brain connectivity based on cerebral oxygenation dynamics (hemodynamic connectivity), whereas [18 F]-fluorodeoxyglucose functional positron emission tomography (FDG-fPET) describes brain connectivity based on cerebral glucose uptake (metabolic connectivity), each providing a unique characterisation of the human brain. How these two modalities differ in their contribution to cognition and behaviour is unclear. We used simultaneous resting-state FDG-fPET/fMRI to investigate how hemodynamic connectivity and metabolic connectivity relate to cognitive function by applying partial least squares analyses. Results revealed that while for both modalities the frontoparietal anatomical subdivisions related the strongest to cognition, using hemodynamic measures this network expressed executive functioning, episodic memory, and depression, while for metabolic measures this network exclusively expressed executive functioning. These findings demonstrate the unique advantages that simultaneous FDG-PET/fMRI has to provide a comprehensive understanding of the neural mechanisms that underpin cognition and highlights the importance of multimodality imaging in cognitive neuroscience research.

neuroscience↗

The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.

evolutionary biology↗

A survey of spiking activity reveals a functional hierarchy of mouse corticothalamic visual areas

The mammalian visual system, from retina to neocortex, has been extensively studied at both anatomical and functional levels. Anatomy indicates the cortico-thalamic system is hierarchical, but characterization of cellular-level functional interactions across multiple levels of this hierarchy is lacking, partially due to the challenge of simultaneously recording activity across numerous regions. Here, we describe a large, open dataset (part of the Allen Brain Observatory) that surveys spiking from units in six cortical and two thalamic regions responding to a battery of visual stimuli. Using spike cross-correlation analysis, we find that inter-area functional connectivity mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas. Classical functional measures of hierarchy, including visual response latency, receptive field size, phase-locking to a drifting grating stimulus, and autocorrelation timescale are all correlated with the anatomical hierarchy. Moreover, recordings during a visual task support the behavioral relevance of hierarchical processing. Overall, this dataset and the hierarchy we describe provide a foundation for understanding coding and dynamics in the mouse cortico-thalamic visual system.

neuroscience↗

Is Drosophila melanogaster Stress Odorant (dSO) really an alarm pheromone?

Social interactions are crucial for the reproduction and survival of many organisms, including those using visual, auditory and olfactory cues to signal the presence of danger. Drosophila melanogaster emits an olfactory alarm signal, termed the Drosophila stress odorant (dSO) in response to mechanical agitation or electric shock, and conspecifics avoid areas previously occupied by stressed individuals. However, the contextual, genetic and neural underpinnings of the emission of, and response to dSO, have received little attention. Using a binary choice assay, we determined that neither age and sex of emitters, nor the time of the day, affected the emission or avoidance of dSO. However, both sex and mating status affected the response to dSO. We also demonstrated that dSO was not species specific so it should not be considered a pheromone but a general alarm signal for Drosophila. However, the response levels to both intra and inter-specific cues differed between species and possible reasons for these differences are discussed. HIGHLIGHTSO_LIEmission of dSO, a highly volatile chemical blend emitted by stressed flies, is not context specific C_LIO_LIResponse to dSO is context specific, affected by factors such as age and mating status. C_LIO_LIAs flies respond to volatiles for stressed heterospecifics, dSO should not be considered an alarm pheromone, but as an alarm cue. C_LI

animal behavior and cognition↗

Spring frost controls spring tree phenology along elevational gradients on the southeastern Tibetan Plateau

Temperature is considered to be a main driver of spring phenology, whereas the role of climate extremes (such as spring frosts) has long been neglected. A large elevational gradient of mature forests on the Tibetan Plateau provides a powerful space-for-time natural experiment to explore driving forces of spring phenology. Combining 5-yr of in situ phenological observations of Smith fir (Abies georgei var. smithii) with concurrent air temperature data along two altitudinal gradients on the southeastern Tibetan Plateau, we tested the hypothesis that spring frost was a major factor regulating the timing of spring phenology. Onset of bud swelling and leaf unfolding in the study years occurred {approx} 18 or 17 days earlier, respectively, at the lowest (3800 m a.s.l.) elevation relative to upper treelines (4360 or 4380 m a.s.l.). The frequency of freezing events and last freezing date were critical factors in determining the timing of bud swelling along two altitudinal gradients, whereas onset of leaf unfolding was primarily controlled by the onset of bud swelling. This finding provides evidence for detrimental impacts of spring frost on spring phenology, which have been underappreciated in research on phenological sensitivity to climate but should be included in phenology models. It contributes to explain the declining global warming effects on spring phenophases, because climatic extreme events (e.g. spring frosts) tend to increase with warming.

ecology↗

Critical minimum temperature limits xylogenesis and maintains treelines on the Tibetan Plateau

Physiological and ecological mechanisms that define treelines are still debated. It is suggested that the absence of trees above the treeline is caused by the low temperature that limits growth. Thus, we raise the hypothesis that there is a critical minimum temperature (CTmin) preventing xylogenesis at treeline. We tested this hypothesis by examining weekly xylogenesis across three and four growing seasons in two natural Smith fir (Abies georgei var. smithii) treeline sites on the south-eastern Tibetan Plateau. Despite differences in the timing of cell differentiation among years, minimum air temperature was the dominant climatic variable associated with xylem growth; the critical minimum temperature (CTmin) for the onset and end of xylogenesis occurred at 0.7{+/-}0.4 {degrees}C. A process-based-modeled chronology of tree-ring formation using this CTmin was consistent with actual tree-ring data. This extremely low CTmin permits Smith fir growing at treeline to complete annual xylem production and maturation and provides both support and a mechanism for treeline formation.

ecology↗