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생존하려면 동물은 감각 정보를 적절한 행동으로 전환해야 합니다1,2. 비전은 행동학적으로 관련된 자극을 찾고 운동 반응을 안내하는 상식입니다3,4,5. 회로가 망막 좌표의 물체 위치를 신체 좌표의 이동 방향으로 변환하는 방법은 아직 거의 알려져 있지 않습니다. 여기에서 우리는 초파리의 행동, 생리학, 해부학 및 연결학을 통해 특징 감지 시각적 투영 뉴런(VPN)6,7의 수상돌기에 의해 형성된 지형 지도를 VPN 출력의 시냅스 중량 구배로 중앙 뇌 뉴런으로 변환함으로써 시각 운동 변형이 발생한다는 것을 보여줍니다. . 우리는 이 그라데이션 모티프가 시각적 어렴풋한 자극의 전후 위치를 파리의 방향 탈출로 변환하는 방법을 보여줍니다. 특히, 우리는 어렴풋이 반응하는 VPN 유형에 대한 시냅스 후의 두 뉴런이 반대 이륙 방향을 촉진한다는 것을 발견했습니다. 서로 다른 시야 영역에 있는 어렴풋한 VPN에서 이러한 뉴런에 대한 반대 시냅스 가중치 구배는 국지적인 어렴풋한 위협을 올바른 방향의 탈출로 변환합니다. 두 번째로 다가오는 반응형 VPN 유형의 경우 배측 배축을 따라 등급별 응답을 보여줍니다. 우리는 이 시냅스 그라데이션 모티프가 20개의 기본 VPN 셀 유형 모두에 걸쳐 일반화되며 VPN 축삭 지형 없이 가장 자주 발생한다는 것을 보여줍니다. 따라서 시냅스 기울기는 감각 정보의 공간적 특징을 지향성 모터 출력으로 전달하기 위한 일반적인 메커니즘일 수 있습니다.
공을 잡거나, 전화를 받을 때 몸을 돌리거나, 컵을 집으려면 우리의 뇌는 무엇을 해야 할지뿐만 아니라 어디서 해야 할지 지시해야 합니다. 이 과정에는 망막 위의 위치와 같이 감각 공간에서 감지된 물체의 위치가 사지나 관절의 방향과 같은 운동 좌표계의 이동 방향으로 변환되는 '감각 운동 변환'2,8,9이 있습니다. 각도가 변경됩니다. 다양한 종의 지형적으로 조직된 뇌 영역이 시각적 개체의 위치와 정체성을 인코딩한다는 상당한 증거가 있습니다. 그러나 신경 연결 패턴이 이러한 정보를 하류 전운동 네트워크에 전달하는 방법과 발달 프로그램이 이러한 연결을 지정하는 방법은 잘 이해되지 않은 상태로 남아 있습니다.
초파리에서 시엽에 수상돌기가 있고 중앙 뇌에 있는 축삭 말단이 있는 VPN은 작은 물체의 움직임이나 어두운 물체의 어렴풋한 출현과 같은 행동학적으로 관련된 시각적 특징을 감지하고 감각 운동 인터페이스. 여러 VPN 유형은 시각적 안내 동작6,18,19,20,21을 시작하고 일부 VPN 유형은 활성화가 별개의 모터 동작을 구동하는 반뇌당 약 500개의 전운동 하강 뉴런(DN)의 하위 집합에 직접 시냅스됩니다. VPN에는 20~30가지 유형이 있으며, 각 VPN은 반뇌당 20~200개의 뉴런으로 구성되어 있으며(그림 1a), 시각적 공간을 함께 덮는 작은 수용 영역(20~40°)이 있습니다6,15,16. 따라서 시신경엽의 VPN 수상돌기는 시각 공간의 지형도를 형성하고, 파리의 망막에 있는 물체 위치는 이론적으로 주어진 유형 내의 VPN 뉴런이 흥분되는 방식으로 인코딩됩니다. 그러나 주어진 유형 내의 모든 VPN의 축삭이 거의 25 또는 6,15 없는 중앙 뇌 내의 좁고 뚜렷한 사구체(그림 1a)로 끝나기 때문에 이 공간 정보가 다운스트림 파트너에게 전달되는지 여부와 방법은 불분명합니다. ,26,27 광학 현미경 수준에서 관찰 가능한 지형. 그러나 여러 VPN 셀 유형은 후진 및 회전, 다른 방향에서 다가오는 자극 탈출, 충돌 회피, 비행 중 시각적 자극으로부터 단속운동 회전 등 방향별 동작과 관련이 있습니다6,28,29,30. 여기에서는 전자 현미경(EM), 광학 현미경, 생리학 및 행동을 사용하여 VPN-시냅스 후 파트너 인터페이스를 탐색하여 방향별 시각 정보가 다운스트림 전운동 네트워크로 변환되는 방법을 조사합니다.
50 postsynaptic neurons typically innervate each optic glomerulus. Inset: EM-based reconstructions (hemibrain connectome27) of 71 LC4 VPNs (blue), a single LC4 neuron (red) and LC4 postsynaptic partner, GF DN (black). VNC, ventral nerve cord; D, dorsal; L, lateral; glom., glomerulus. Scale bar, 20 μm. b, Confocal projections of GFP (green) expression in seven DNs innervating the LC4 glomerulus (red dashed line). Grey, brain neuropils. Images adapted from ref. 24, CC BY 4.0 (n = 4 brains for each DN). Scale bar, 50 μm. c, Synaptic connectivity from looming-sensitive VPN cell types onto seven DNs based on the hemibrain connectome. Arrow width is proportional to synapse number. Pie charts indicate proportion of a given DN's inputs from each looming-sensitive VPN cell type. d, Forward–backward postural shifts in response to DN photostimulation; quantified as Δ[T2 leg angle], the change in angle between the middle jumping legs and COM. e, Δ[T2 leg angle] 75 ms after the onset of 50-ms photostimulation. Points, individual flies; error bars, s.d.; one-way analysis of variance (ANOVA), Dunnett's test, ***P < 0.001, exact P values in Supplementary Table 1. f, Δ[T2 leg angle] time courses from machine-learning-tracked data; red shaded area, photostimulation period. g, Δ[T2 leg angle] for a subset of manually annotated flies. In f,g: lines, mean; shading, s.d. h, Takeoff direction is COM movement direction between onset of middle leg extension and takeoff. i, Polar histograms of optogenetically activated takeoff direction. Red line, circular mean; n, number of flies tested; \(\bar{R}\), mean vector length; P, Hodges–Ajne test for angular uniformity./p>90%), suggesting that natural threats may simultaneously activate multiple LC4-DNs to drive downstream escape motor circuits. DNp04- and DNp11-activated takeoffs were almost exclusively ‘long-mode’, in which the wings are raised before the takeoff jump, whereas GF activation produced ‘short-mode’ escapes without prior wing-raising as previously described36 (Extended Data Fig. 1g,h and Supplementary Table 1). Combination line activation drove primarily long-mode takeoff, but did also unexpectedly produce many short-mode takeoffs, which are thought to rely on GF activation. Taken together with the findings of our previous work37, this mixed result indicates either that the combination of DNp02, DNp04 and DNp06 inputs to the GFs, or that these DNs are not naturally co-activated with the strong intensity of optogenetic activation./p> 0.05). m, GF depolarization responses from localized activation of dorsal versus ventral LPLC2 and LC4 neurons expressing the P2X2 receptor. Left: representative GF responses (n = 5, one fly); individual (lighter-coloured lines) and averaged (darker lines) responses. Right: comparison of normalized average GF responses (resp.) to dorsal versus ventral VPN activation (two-tailed paired t-test; error bars, s.e.m., *P ≤ 0.05, ****P < 0.0001). Responses were averaged during the late response peak; see Extended Data Fig. 12c for quantification of the early peak. n, individual flies tested. A, anterior; P, posterior; D, dorsal; V, ventral; L, lateral; M, medial. All box plots show median and interquartile range./p> 0.05, *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001 for all figures where applicable. Statistical tests for Figs. 1e and 3e,h and Extended Data Figs. 1,2,4 and 12 are described in Supplementary Table 1. In all box plots (Fig. 6 and Extended Data Fig. 11), the solid line depicts the median; the upper and lower bounds of the box depict the third and first quantiles of the data spread, respectively. Whiskers indicate minimum and maximum values. All other statistical tests, number of replicates, statistical significance levels and other elements of statistical analysis are reported in the corresponding section of the Methods, along with the associated results and/or in the corresponding figure legends. No data were excluded from the analysis except as noted for the behaviour experiments (see the section in the Methods entitled Behavioural data analysis). All measurements were taken from distinct samples./p>Kir2.1. One trial per fly. b, Some flies also takeoff in response to looming, and those that do takeoff in a direction away from the stimulus (with some influence of the heading of the fly33). Shown are polar takeoff direction histograms with 12° bin width and mean resultant vector overlaid (red line). p, Hodges-Ajne test for angular uniformity. c, Takeoff direction results from the fly shifting its COM relative to the axes formed by a line connecting the ground contact points of its two middle jumping legs and a perpendicular bisector. Black points indicate COM at stimulus onset and red points indicate COM just prior to takeoff. d, The specific direction in which the COM moves in body coordinates depends on its starting location. Vector position is the COM position at stimulus onset. The vector itself indicates the shift of COM position from stimulus onset to just prior to takeoff. Black vectors are tracked data, gray vectors are interpolated. Black square is approximated point of convergence. e, Percent of flies (individual DN driver lines) that performed a takeoff in response to CsChrimson optogenetic activation in the FlyPEZ assay. Error bars, Wilson score interval; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 vs control (Empty, empty brain split-Gal4 control; DL – wild type control); normal approximation to binomial, two-sided Z-test, Bonferroni correction post hoc test. f, Same data as in (e) but with driver lines grouped by cell type. Error bars, SD. g, Histograms displaying the distribution of escape sequence durations between the wing raising and takeoff jump sub-behaviors (for LC4-DN driver lines expressing CsChrimson that can elicit escape upon activation). Escape trials are combined from split-Gal4 lines for each LC4-DN type. Short-mode escape duration (0 to 7 ms, gray shaded region) and long-mode escape duration (>7 ms), as previously established. h, Percentage of short-mode activated escapes. Error bars, Wilson score interval; ****p < 0.0001 versus GF; normal approximation to binomial, two-sided Z-test, Bonferroni correction post hoc test. Detailed description of statistical tests used and p-values for panels "e" and "h" is available in Supplementary Table 1./p> 0.1 for both DNs, Kuiper's Test). However, DN silencing altered the distribution of backward takeoffs direction in response to frontal looming (0°) for both DNp02 (p < 0.005, Kuiper's test) and DNp11 (p < 0.001, Kuiper's test) silencing compared to controls. Strikingly, many DNp02- and DNp11-silenced flies performed forward takeoffs in response to frontal looming stimulation, effectively jumping toward the threatening stimulus. c, To further understand why flies were inappropriately taking off forwards, we looked at how much DN-silenced flies moved their COM backwards in response to 0° looming. We visualized COM movement in body coordinates from different starting postures using the same flow fields in body-centric coordinates as in Extended Data Fig. 1d. Visual inspection indicated that COM movement fields for DN-silenced flies differed from controls in the amount of backwards movement and had more lateral movement. d, To quantify this motion, we measure the T2 angle (angle formed by T2 tarsal contact points and COM), which is >180° when the COM is in front of the T2 jumping legs and <180° when the COM is behind the T2 jumping legs. The mean T2 angle just before takeoff was significantly different for DNp02- and DNp11-silenced flies compared to controls (*p = 0.0468, ***p = 4.79e-04, One-Way ANOVA, Dunnett's test). Black points, individual flies; error bars, SD. e, Looking at time courses for T2 leg angle in response to 0° azimuth looming stimulus for the different DN-silenced lines (colors, shaded area, SD), with control data overlaid (grey), it is clear that the difference in the DN-silenced flies is that they do not shift backwards as much as controls. Since COM placement prior to takeoff determines whether the fly's jump will propel it forwards (T2 angle>180) or backwards (T2 angle<180), the impaired pre-takeoff T2 leg angle change in DNp02- and DNp11-silenced flies, which on average does not become <180° as in control flies, likely underlies altered takeoff performance leading to more forward-directed takeoffs. f, DNp02 and DNp11 silencing does not affect takeoff rates. Percentage of flies which performed a takeoff to a looming visual stimulus (azimuth = 90°, elevation = 45°) at four looming rates (l/v = 10, 20, 40 and 80 ms), or a looming visual stimulus (azimuth = 0° or 180°, elevation = 45°) at l/v = 40. L1/L2-silenced flies serve as "motion-blind" negative controls. Error bars, SEM; Wilson score interval; **p < 0.01, ***p < 0.001, ****p < 0.0001 versus Empty control; normal approximation to binomial, two-sided Z-test, Bonferroni correction post hoc test. Detailed description of statistical tests and p-values for panel "f" is available in Supplementary Table 1./p>50 synapses total. c, Representative examples of graded synaptic connectivity between four VPN cell types and their top 15 postsynaptic partners based on the total number of synapses. Each individual neuron within a VPN cell type is assigned a color based on just one plot (DNp11 for LC4, Giant Fiber for LPLC2 etc.), with the colors preserved in other graphs. Every plot indicates the number of synapses between individual neurons within one VPN cell type and a given postsynaptic partner (arranged by descending number of synapses). d, Single LC4 neurons (EM-based connectome reconstructions) with dendrites in anterior (bodyID 1907587934) or posterior (bodyID 1249932198) regions of the lobula are highlighted. The remaining LC4 neurons shown in grey. e, Differential synaptic connectivity between two LC4 neurons from (d) and their top 25 postsynaptic partners (measured by total number of synapses). 15 out of 25 postsynaptic neurons receive preferential or exclusive input from either anterior or posterior LC4. f–g, Differential synaptic connectivity of individual LPLC2 neurons with dendrites in dorsal (bodyID 1815826155) vs ventral (bodyID 1815809293) lobula. Similar to (d, e). P, posterior; M, medial; D, dorsal; L, lateral./p>0.05; *: P <0.05; **: P <0.01; ****: P <0.0001. Detailed description of statistical tests and p-values for panels is available in Supplementary Table 1./p>
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