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年终盘点：2019年神经活动记录十大基础研究进展
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2019年神经活动记录十大基础研究进展
1. Cell—科学家开发下一代四色遗传编码性钙离子探针XCaMPs用于不同神经元类群的同步成像
英文摘要：
Todecipher dynamic brain information processing, current genetically encodedcalcium indicators (GECIs) are limited in single action potential (AP) detectionspeed, combinatorial spectral compatibility, and two-photon imaging depth. Toaddress this, here, we rationally engineered a next-generation quadricolor GECIsuite, XCaMPs. Single AP detection was achieved within 3-10 ms of spike onset,enabling measurements of fast-spike trains in parvalbumin (PV)-positiveinterneurons in the barrel cortex in vivo and recording three distinct (twoinhibitory and one excitatory) ensembles during pre-motion activity in freelymoving mice. In vivo paired recording of pre- and postsynaptic firing revealedspatiotemporal constraints of dendritic inhibition in layer 1 in vivo, betweenaxons of somatostatin (SST)-positive interneurons and apical tufts dendrites ofexcitatory pyramidal neurons. Finally, non-invasive, subcortical imaging usingred XCaMP-R uncovered somatosensation-evoked persistent activity in hippocampalCA1 neurons. Thus, the XCaMPs offer a critical enhancement of solution space instudies of complex neuronal circuit dynamics.
参考文献：
Inoueet al (2019). Rational Engineering of XCaMPs, a Multicolor GECI Suite for InVivo Imaging of Complex Brain Circuit Dynamics. Cell. 2019 May16;177(5):1346-1360.e24.
2.Science—科学家成功给小鼠大脑中插入了幻觉：皮层特异的神经元动力学驱动小鼠的认知决策
英文摘要：
Perceptualexperiences may arise from neuronal activity patterns in mammalian neocortex. We probed mouseneocortex during visual discrimination using a red-shifted channelrhodopsin(ChRmine, discovered through structure-guided genome mining) alongsidemultiplexed multiphoton-holography (MultiSLM), achieving control ofindividually specified neurons spanning large cortical volumes with millisecondprecision. Stimulating a critical number of stimulus-orientation-selectiveneurons drove widespread recruitment of functionally related neurons, a processenhanced by (but not requiring) orientation-discrimination task learning.Optogenetic targeting of orientation-selective ensembles elicited correctbehavioral discrimination. Cortical layer-specific dynamics were apparent, asemergent neuronal activityasymmetrically propagated from layer 2/3 to layer 5, and smaller layer 5ensembles were as effective as larger layer 2/3 ensembles in elicitingorientation discrimination behavior. Population dynamics emerging afteroptogenetic stimulation both correctly predicted behavior and resembled naturalinternal representations of visual stimuli at cellular resolution over volumesof cortex.
参考文献：
Marshelet al (2019). Cortical layer-specific critical dynamics triggering perception. Science.2019 Aug 9;365(6453).
3.Cell—关系好不好，看一看大脑活动就知道：科学家在小鼠社交性行为的神经元同步活动方面取得了突破性进展
英文摘要：
Socialinteractions involve complex decision-making tasks that are shaped by dynamic,mutual feedback between participants. An open question is whether and howemergent properties may arise across brains of socially interacting individualsto influence social decisions. By simultaneously performing microendoscopiccalcium imaging in pairs of socially interacting mice, we find that animalsexhibit interbrain correlations of neural activityin the prefrontal cortex that are dependent on ongoing social interaction. Activity synchrony arises from two neuronal populations that separately encode one's ownbehaviors and those of the social partner. Strikingly, interbrain correlationspredict future social interactions as well as dominance relationships in acompetitive context. Together, our study provides conclusive evidence forinterbrain synchrony in rodents, uncovers how synchronization arises from activity at the single-cell level, and presents a rolefor interbrain neural activity coupling as aproperty of multi-animal systems in coordinating and sustaining socialinteractions between individuals.
参考文献：
Kingsburyet al (2019). Correlated Neural Activity and Encoding of Behavior across Brainsof Socially Interacting Animals. Cell. 2019 Jul 11;178(2):429-446.e16.
4.Nature—复杂动力学的重要作用：科学家揭示了运动皮层短期记忆引导未来运动的吸引子动力学原理
英文摘要：
Short-termmemories link events separated in time, such as past sensation and futureactions. Short-term memories are correlated with slow neural dynamics,including selective persistent activity, which can be maintained over seconds.In a delayed response task that requires short-term memory, neurons in themouse anterior lateral motor cortex (ALM) show persistent activity thatinstructs future actions. To determine the principles that underlie thispersistent activity, here we combined intracellular and extracellular electrophysiology with optogenetic perturbations andnetwork modelling. We show that during the delay epoch, the activity of ALMneurons moved towards discrete end points that correspond to specific movementdirections. These end points were robust to transient shifts in ALM activitycaused by optogenetic perturbations. Perturbations occasionally switched thepopulation dynamics to the other end point, followed by incorrect actions. Ourresults show that discrete attractor dynamics underlie short-term memoryrelated to motor planning.
参考文献：
Inagakiet al (2019). Discrete attractor dynamics underlies persistent activity in thefrontal cortex. Nature. 2019 Feb;566(7743):212-217.
5.Science—比CNO更特异更高效：科学家开发新的化学遗传系统药物uPSEMs用于神经元的激活和抑制
英文摘要：
Chemogenetics enables noninvasive chemical control over cellpopulations in behaving animals. However, existing small-molecule agonists showinsufficient potency or selectivity. There is also a need for chemogeneticsystems compatible with both research and human therapeutic applications. Wedeveloped a new ion channel-based platform for cell activation and silencingthat is controlled by low doses of the smoking cessation drug varenicline. Wethen synthesized subnanomolar-potency agonists, called uPSEMs, with highselectivity for the chemogenetic receptors. uPSEMs and their receptors werecharacterized in brains of mice and a rhesus monkey by in vivo electrophysiology, calcium imaging, positron emissiontomography, behavioral efficacy testing, and receptor counterscreening. Thisplatform of receptors and selective ultrapotent agonists enables potentialresearch and clinical applications of chemogenetics.
参考文献：
Magnuset al (2019). Ultrapotent chemogenetics for research and potential clinicalapplications. Science. 2019 Apr 12;364(6436). pii: eaav5282.
6.Science—科学家开发新型遗传编码性电压探针Voltron，可用于小鼠、斑马鱼和果蝇的在体神经元活动记录
英文摘要：
Geneticallyencoded voltage indicators (GEVIs) enable monitoring of neuronalactivity at high spatial and temporal resolution.However, the utility of existing GEVIs has been limited by the brightness andphotostability of fluorescent proteins and rhodopsins. We engineered a GEVI,called Voltron, that uses bright and photostable synthetic dyes instead of protein-basedfluorophores, thereby extending the number of neurons imaged simultaneously invivo by a factor of 10 and enabling imaging for significantly longer durationsrelative to existing GEVIs. We used Voltron for in vivo voltage imaging inmice, zebrafish, and fruit flies. In the mouse cortex, Voltron allowedsingle-trial recording of spikes and subthreshold voltage signals from dozensof neurons simultaneously over a 15-minute period of continuous imaging. Inlarval zebrafish, Voltron enabled the precise correlation of spike timing withbehavior.
参考文献：
Abdelfattahet al (2019). Bright and photostable chemigenetic indicators for extended invivo voltage imaging. Science. 2019 Aug 16;365(6454):699-704.
7.Science—Delta波的功能被首次阐明：Delta通过隔离皮层计算进而促进记忆巩固
英文摘要：
Deltawaves have been described as periods of generalized silence across the cortex,and their alternation with periods of endogenous activityresults in the slow oscillation of slow-wave sleep. Despite evidence that deltawaves are instrumental for memory consolidation, their specific role inreshaping cortical functional circuits remains puzzling. In a rat model, wefound that delta waves are not periods of complete silence and that theresidual activity is not mere neuronal noise. Instead, cortical cells involved inlearning a spatial memory task subsequently formed cell assemblies during deltawaves in response to transient reactivation of hippocampal ensembles duringripples. This process occurred selectively during endogenous or induced memoryconsolidation. Thus, delta waves represent isolated cortical computationstightly related to ongoing information processing underlying memoryconsolidation.
参考文献：
Todorovaet al (2019). Isolated cortical computations during delta waves support memoryconsolidation.
Science.2019 Oct 18;366(6463):377-381.
8.Nat Nanotechnol—纳米技术大显身手：科学家开发新型纳米晶体管探针用于高效神经元细胞内记录
英文摘要：
Newtools for intracellular electrophysiology thatpush the limits of spatiotemporal resolution while reducing invasiveness couldprovide a deeper understanding of electrogenic cells and their networks intissues, and push progress towards human-machine interfaces. Althoughsignificant advances have been made in developing nanodevices for intracellularprobes, current approaches exhibit a trade-off between device scalability andrecording amplitude. We address this challenge by combining deterministicshape-controlled nanowire transfer with spatially definedsemiconductor-to-metal transformation to realize scalable nanowire field-effecttransistor probe arrays with controllable tip geometry and sensor size, whichenable recording of up to 100 mV intracellular action potentials from primaryneurons. Systematic studies on neurons and cardiomyocytes show that controllingdevice curvature and sensor size is critical for achieving high-amplitudeintracellular recordings. In addition, this device design allows formultiplexed recording from single cells and cell networks and could enablefuture investigations of dynamics in the brain and other tissues.
参考文献：
Zhaoet al (2019). Scalable ultrasmall three-dimensional nanowire transistor probesfor intracellular recording. NatNanotechnol. 2019 Aug;14(8):783-790.
9. Cell—科学家开发出新型电压探针ASAP3，可用于清醒活动小鼠的实时双光子成像
英文摘要：
Opticalinterrogation of voltage in deep brain locations with cellular resolution wouldbe immensely useful for understanding how neuronal circuits processinformation. Here, we report ASAP3, a genetically encoded voltage indicatorwith 51% fluorescence modulation by physiological voltages, submillisecondactivation kinetics, and full responsivity under two-photon excitation. We alsointroduce an ultrafast local volume excitation (ULoVE) method forkilohertz-rate two-photon sampling in vivo with increased stability andsensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we showsingle-trial tracking of spikes and subthreshold events for minutes in deeplocations, with subcellular resolution and with repeated sampling over days. Inthe visual cortex, we use soma-targeted ASAP3 to illustrate cell-type-dependentsubthreshold modulation by locomotion. Thus, ASAP3 and ULoVE enable high-speedoptical recording of electrical activity in genetically defined neurons at deeplocations during awake behavior.
参考文献：
Villetteet al (2019). Ultrafast Two-Photon Imaging of a High-Gain Voltage Indicator inAwake Behaving Mice. Cell. 2019 Dec 12;179(7):1590-1608.e23.
10.Nature—科学家开发出新型电压探针SomArchon，可用于清醒活动小鼠的神经元集群活动成像
英文摘要：
Alongstanding goal in neuroscience has been to image membrane voltage across apopulation of individual neurons in an awake, behaving mammal. Here we describea genetically encoded fluorescent voltage indicator, SomArchon, which exhibitsmillisecond response times and is compatible with optogenetic control, andwhich increases the sensitivity, signal-to-noise ratio, and number of neuronsobservable several-fold over previously published fully genetically encodedreagents1-8. Under conventional one-photon microscopy, SomArchonenables the routine population analysis of around 13 neurons at once, inmultiple brain regions (cortex, hippocampus, and striatum) of head-fixed, awake,behaving mice. Using SomArchon, we detected both positive and negativeresponses of striatal neurons during movement, as previously reported by electrophysiology but not easily detected using moderncalcium imaging techniques9-11, highlighting the power of voltageimaging to reveal bidirectional modulation. We also examined how spikes relateto the subthreshold theta oscillations of individual hippocampal neurons, withSomArchon showing that the spikes of individual neurons are more phase-lockedto their own subthreshold theta oscillations than to local field potentialtheta oscillations. Thus, SomArchon reports both spikes and subthresholdvoltage dynamics in awake, behaving mice.
参考文献：
Piatkevichet al (2019). Population imaging of neural activity in awake behaving mice. Nature.2019 Oct;574(7778):413-417.
2019年十大研究进展名录
6. 年终盘点：2019年抑郁症领域十大基础研究进展（一半来自中国）
2018年十大研究进展名录
14. 2018年的十大睡眠研究突破
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