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Nearest neighbours reveal fast and slow components of motor learning 期刊论文
NATURE, 2020, 577 (7791) : 526-+
作者:  Kollmorgen, Sepp;  Hahnloser, Richard H. R.;  Mante, Valerio
收藏  |  浏览/下载:4/0  |  提交时间:2020/07/03

A new method for analysing change in high-dimensional data is based on nearest-neighbour statistics and is applied here to song dynamics during vocal learning in zebra finches, but could potentially be applied to other biological and artificial behaviours.


Changes in behaviour resulting from environmental influences, development and learning(1-5) are commonly quantified on the basis of a few hand-picked features(2-4,6,7) (for example, the average pitch of acoustic vocalizations(3)), assuming discrete classes of behaviours (such as distinct vocal syllables)(2,3,8-10). However, such methods generalize poorly across different behaviours and model systems and may miss important components of change. Here we present a more-general account of behavioural change that is based on nearest-neighbour statistics(11-13), and apply it to song development in a songbird, the zebra finch(3). First, we introduce the concept of '  repertoire dating'  , whereby each rendition of a behaviour (for example, each vocalization) is assigned a repertoire time, reflecting when similar renditions were typical in the behavioural repertoire. Repertoire time isolates the components of vocal variability that are congruent with long-term changes due to vocal learning and development, and stratifies the behavioural repertoire into '  regressions'  , '  anticipations'  and '  typical renditions'  . Second, we obtain a holistic, yet low-dimensional, description of vocal change in terms of a stratified '  behavioural trajectory'  , revealing numerous previously unrecognized components of behavioural change on fast and slow timescales, as well as distinct patterns of overnight consolidation(1,2,4,14,15) across the behavioral repertoire. We find that diurnal changes in regressions undergo only weak consolidation, whereas anticipations and typical renditions consolidate fully. Because of its generality, our nonparametric description of how behaviour evolves relative to itself-rather than to a potentially arbitrary, experimenter-defined goal(2,3,14,16)-appears well suited for comparing learning and change across behaviours and species(17,18), as well as biological and artificial systems(5).


  
Single-chain heteropolymers transport protons selectively and rapidly 期刊论文
NATURE, 2020, 577 (7789) : 216-+
作者:  Jiang, Tao;  Hall, Aaron;  Eres, Marco;  Hemmatian, Zahra;  Qiao, Baofu;  Zhou, Yun;  Ruan, Zhiyuan;  Couse, Andrew D.;  Heller, William T.;  Huang, Haiyan;  de la Cruz, Monica Olvera;  Rolandi, Marco;  Xu, Ting
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels(1,2), both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks(3-13). However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs)(14) can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains(15,16) for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.


  
Where I work 期刊论文
NATURE, 2020, 582 (7813) : 600-600
作者:  Bodin, Madeline;  Khan, Christin
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

US federal biologist Christin Khan embraces risk above the Atlantic Ocean to monitor a rare species.


US federal biologist Christin Khan embraces risk above the Atlantic Ocean to monitor a rare species.


  
IL-17a promotes sociability in mouse models of neurodevelopmental disorders 期刊论文
NATURE, 2020, 577 (7789) : 249-+
作者:  Reed, Michael Douglas;  Yim, Yeong Shin;  Wimmer, Ralf D.;  Kim, Hyunju;  Ryu, Changhyeon;  Welch, Gwyneth Margaret;  Andina, Matias;  King, Hunter Oren;  Waisman, Ari;  Halassa, Michael M.;  Huh, Jun R.;  Choi, Gloria B.
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

A subset of children with autism spectrum disorder appear to show an improvement in their behavioural symptoms during the course of a fever, a sign of systemic inflammation(1,2). Here we elucidate the molecular and neural mechanisms that underlie the beneficial effects of inflammation on social behaviour deficits in mice. We compared an environmental model of neurodevelopmental disorders in which mice were exposed to maternal immune activation (MIA) during embryogenesis(3,4) with mouse models that are genetically deficient for contactin-associated protein-like 2 (Cntnap2)(5), fragile X mental retardation-1 (Fmr1)(6) or Sh3 and multiple ankyrin repeat domains 3 (Shank3)(7). We establish that the social behaviour deficits in offspring exposed to MIA can be temporarily rescued by the inflammatory response elicited by the administration of lipopolysaccharide (LPS). This behavioural rescue was accompanied by a reduction in neuronal activity in the primary somatosensory cortex dysgranular zone (S1DZ), the hyperactivity of which was previously implicated in the manifestation of behavioural phenotypes associated with offspring exposed to MIA(8). By contrast, we did not observe an LPS-induced rescue of social deficits in the monogenic models. We demonstrate that the differences in responsiveness to the LPS treatment between the MIA and the monogenic models emerge from differences in the levels of cytokine production. LPS treatment in monogenic mutant mice did not induce amounts of interleukin-17a (IL-17a) comparable to those induced in MIA offspring  bypassing this difference by directly delivering IL-17a into S1DZ was sufficient to promote sociability in monogenic mutant mice as well as in MIA offspring. Conversely, abrogating the expression of IL-17 receptor subunit a (IL-17Ra) in the neurons of the S1DZ eliminated the ability of LPS to reverse the sociability phenotypes in MIA offspring. Our data support a neuroimmune mechanism that underlies neurodevelopmental disorders in which the production of IL-17a during inflammation can ameliorate the expression of social behaviour deficits by directly affecting neuronal activity in the central nervous system.


  
Internal state dynamics shape brainwide activity and foraging behaviour 期刊论文
NATURE, 2020, 577 (7789) : 239-+
作者:  Marques, Joao C.;  Li, Meng;  Schaak, Diane;  Robson, Drew N.;  Li, Jennifer M.
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/03

The brain has persistent internal states that can modulate every aspect of an animal'  s mental experience(1-4). In complex tasks such as foraging, the internal state is dynamic(5-8). Caenorhabditis elegans alternate between local search and global dispersal(5). Rodents and primates exhibit trade-offs between exploitation and exploration(6,7). However, fundamental questions remain about how persistent states are maintained in the brain, which upstream networks drive state transitions and how state-encoding neurons exert neuromodulatory effects on sensory perception and decision-making to govern appropriate behaviour. Here, using tracking microscopy to monitor whole-brain neuronal activity at cellular resolution in freely moving zebrafish larvae(9), we show that zebrafish spontaneously alternate between two persistent internal states during foraging for live prey (Paramecia). In the exploitation state, the animal inhibits locomotion and promotes hunting, generating small, localized trajectories. In the exploration state, the animal promotes locomotion and suppresses hunting, generating long-ranging trajectories that enhance spatial dispersion. We uncover a dorsal raphe subpopulation with persistent activity that robustly encodes the exploitation state. The exploitation-state-encoding neurons, together with a multimodal trigger network that is associated with state transitions, form a stochastically activated nonlinear dynamical system. The activity of this oscillatory network correlates with a global retuning of sensorimotor transformations during foraging that leads to marked changes in both the motivation to hunt for prey and the accuracy of motor sequences during hunting. This work reveals an important hidden variable that shapes the temporal structure of motivation and decision-making.


  
Ensuring meiotic DNA break formation in the mouse pseudoautosomal region 期刊论文
NATURE, 2020
作者:  Schuessler, R. X.;  Bekker, H.;  Brass, M.;  Cakir, H.;  Crespo Lopez-Urrutia, J. R.;  Door, M.;  Filianin, P.;  Harman, Z.;  Haverkort, M. W.;  Huang, W. J.;  Indelicato, P.;  Keitel, C. H.;  Koenig, C. M.;  Kromer, K.;  Mueller, M.;  Novikov, Y. N.;  Rischka, A.;  Schweiger, C.;  Sturm, S.;  Ulmer, S.;  Eliseev, S.;  Blaum, K.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

In mice, the pseudoautosomal region of the sex chromosomes undergoes a dynamic structural rearrangement to promote a high rate of DNA double-strand breaks and to ensure X-Y recombination.


Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation(1,2). How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyperaccumulate in the PAR, its chromosome axes elongate and the sister chromatids separate. These processes are linked to heterochromatic mo-2 minisatellite arrays, and require MEI4 and ANKRD31 proteins but not the axis components REC8 or HORMAD1. We propose that the repetitive DNA sequence of the PAR confers unique chromatin and higher-order structures that are crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, notably, oocytes can be reprogrammed to exhibit spermatocyte-like levels of DSBs in the PAR simply by delaying or preventing synapsis. Thus, the sexually dimorphic behaviour of the PAR is in part a result of kinetic differences between the sexes in a race between the maturation of the PAR structure, formation of DSBs and completion of pairing and synapsis. Our findings establish a mechanistic paradigm for the recombination of sex chromosomes during meiosis.


  
A neurotransmitter produced by gut bacteria modulates host sensory behaviour 期刊论文
NATURE, 2020
作者:  Zhao, Xiaoxu;  Song, Peng;  Wang, Chengcai;  Riis-Jensen, Anders C.;  Fu, Wei;  Deng, Ya;  Wan, Dongyang;  Kang, Lixing;  Ning, Shoucong;  Dan, Jiadong;  Venkatesan, T.;  Liu, Zheng;  Zhou, Wu;  Thygesen, Kristian S.;  Luo, Xin;  Pennycook, Stephen J.;  Loh, Kian Ping
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

A neuromodulator produced by commensalProvidenciabacteria that colonize the gut ofCaenorhabditis elegansmimics the functions of the cognate host molecule to manipulate a sensory decision of the host.


Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms(1). Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts(2,3). However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that inCaenorhabditis elegans, the neuromodulator tyramine produced by commensalProvidenciabacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine beta-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis inProvidencia, and show that these genes are necessary for the modulation of host behaviour. We further find thatC. eleganscolonized byProvidenciapreferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.


  
Hidden neural states underlie canary song syntax 期刊论文
NATURE, 2020
作者:  Bao, Han;  Duan, Junlei;  Jin, Shenchao;  Lu, Xingda;  Li, Pengxiong;  Qu, Weizhi;  Wang, Mingfeng;  Novikova, Irina;  Mikhailov, Eugeniy E.;  Zhao, Kai-Feng;  Molmer, Klaus;  Shen, Heng;  Xiao, Yanhong
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Neurons in the canary premotor cortex homologue encode past song phrases and transitions, carrying information relevant to future choice of phrases as '  hidden states'  during song.


Coordinated skills such as speech or dance involve sequences of actions that follow syntactic rules in which transitions between elements depend on the identities and order of past actions. Canary songs consist of repeated syllables called phrases, and the ordering of these phrases follows long-range rules(1)in which the choice of what to sing depends on the song structure many seconds prior. The neural substrates that support these long-range correlations are unknown. Here, using miniature head-mounted microscopes and cell-type-specific genetic tools, we observed neural activity in the premotor nucleus HVC(2-4)as canaries explored various phrase sequences in their repertoire. We identified neurons that encode past transitions, extending over four phrases and spanning up to four seconds and forty syllables. These neurons preferentially encode past actions rather than future actions, can reflect more than one song history, and are active mostly during the rare phrases that involve history-dependent transitions in song. These findings demonstrate that the dynamics of HVC include '  hidden states'  that are not reflected in ongoing behaviour but rather carry information about prior actions. These states provide a possible substrate for the control of syntax transitions governed by long-range rules.


  
Observation of Bose-Einstein condensates in an Earth-orbiting research lab 期刊论文
NATURE, 2020, 582 (7811) : 103-+
作者:  Yamamoto, Keisuke;  Venida, Anthony;  Yano, Julian;  Biancur, Douglas E.;  Kakiuchi, Miwako;  Gupta, Suprit;  Sohn, Albert S. W.;  Mukhopadhyay, Subhadip;  Lin, Elaine Y.;  Parker, Seth J.;  Banh, Robert S.;  Paulo, Joao A.;  Wen, Kwun Wah;  Debnath, Jayanta;  Kim, Grace E.;  Mancias, Joseph D.;  Fearon, Douglas T.;  Perera, Rushika M.;  Kimmelman, Alec C.
收藏  |  浏览/下载:25/0  |  提交时间:2020/07/03

Quantum mechanics governs the microscopic world, where low mass and momentum reveal a natural wave-particle duality. Magnifying quantum behaviour to macroscopic scales is a major strength of the technique of cooling and trapping atomic gases, in which low momentum is engineered through extremely low temperatures. Advances in this field have achieved such precise control over atomic systems that gravity, often negligible when considering individual atoms, has emerged as a substantial obstacle. In particular, although weaker trapping fields would allow access to lower temperatures(1,2), gravity empties atom traps that are too weak. Additionally, inertial sensors based on cold atoms could reach better sensitivities if the free-fall time of the atoms after release from the trap could be made longer(3). Planetary orbit, specifically the condition of perpetual free-fall, offers to lift cold-atom studies beyond such terrestrial limitations. Here we report production of rubidium Bose-Einstein condensates (BECs) in an Earth-orbiting research laboratory, the Cold Atom Lab. We observe subnanokelvin BECs in weak trapping potentials with free-expansion times extending beyond one second, providing an initial demonstration of the advantages offered by a microgravity environment for cold-atom experiments and verifying the successful operation of this facility. With routine BEC production, continuing operations will support long-term investigations of trap topologies unique to microgravity(4,5), atom-laser sources(6), few-body physics(7,8)and pathfinding techniques for atom-wave interferometry(9-12).


  
Cellular locomotion using environmental topography 期刊论文
NATURE, 2020
作者:  Fernandez, Diego Carlos;  Komal, Ruchi;  Langel, Jennifer;  Ma, Jun;  Duy, Phan Q.;  Penzo, Mario A.;  Zhao, Haiqing;  Hattar, Samer
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Within three-dimensional environments, leukocytes can migrate even in the complete absence of adhesive forces using the topographical features of the substrate to propel themselves.


Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces(1). Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour.