Wiring specificity in the direction-selectivity circuit of the retina

Briggman, Kevin L.; Helmstaedter, Moritz; Denk, Winfried

doi:10.1038/nature09818

Cited by 782 publications

(891 citation statements)

References 51 publications

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“…Prior to eye-opening, there is an increase in the number of functional inhibitory synapses from the null-oriented SAC processes to DSGCs [7,16,17]. In adult, serial EM reconstructions indicate that a given SAC branch, which is activated most strongly by centrifugal motion, preferentially but not exclusively synapses onto one DSGC subtype [34]. Therefore, one possibility is that after dark-rearing, the wiring of SACs to DSGCs is less precise in that a given SAC branch is not as particular and forms many synapses with different DSGCs and thus a given DSGC receives inputs from SAC branches of different orientations.…”

Section: Potential Activity-dependent Mechanismsmentioning

confidence: 99%

Role for Visual Experience in the Development of Direction-Selective Circuits

Bos¹,

Gainer²,

Feller³

2017

Current Biology

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SUMMARYVisually-guided behavior can depend critically on detecting the direction of object movement. This computation is first performed in the retina where direction is encoded by direction-selective ganglion cells (DSGCs) that respond strongly to an object moving in the preferred direction and weakly to an object moving in the opposite, or null, direction (reviewed in [1]). These DSGCs come in multiple types that are classified based on their morphologies, response properties and targets in the brain. This study focuses on two types -ON and ON-OFF DSGCs. Though animals can sense motion in all directions, the preferred directions of DSGCs in adult retina cluster along distinct directions that we refer to as the cardinal axes. ON DSGCs have three cardinal axestemporal, ventral and dorsonasal -while ON-OFF DSGCs have four -nasal, temporal, dorsal, and ventral. How these preferred directions emerge during development is still not understood. Several studies have demonstrated that ON [2] and ON-OFF DSGCs are well tuned at eye-opening, and even a few days prior to eye-opening, in rabbits [3], rats [4] and mice [5][6][7][8], suggesting that visual experience is not required to produce direction selective tuning. However, here we show that at eye-opening the preferred directions of both ON and ON-OFF DSGCs are diffusely distributed and that visual deprivation prevents the preferred directions from clustering along the cardinal axes. Our findings indicate a critical role for visual experience in shaping responses in the retina. HHS Public Access RESULTS Clustering of DSGC preferred directions along cardinal axes after eye-opening requires visual experienceWe used two-photon calcium imaging to study the development of DSGC populations in mouse retina. This imaging technique has proven to be quite powerful in characterizing the receptive field properties of retinal ganglion cells [9][10][11][12]. We loaded retinas of WT mice near eye-opening (P13-P14) and in adulthood (>P30) with the calcium dye Oregon green 488 BAPTA-1 hexapotassium salt (OGB-1) via electroporation, thus uniformly labeling the ganglion cell layer ( Figure 1A; see Supplemental Information). Ventral portions of the retina were stimulated with light centered at 385 nm to maximally activate UV-cones [13,14] while minimizing cross talk with the imaging detectors ( Figure S1). This approach allowed us to record from all DSGC subtypes within a single field of view (~40000 μm 2 ).To identify DSGCs, we first used full field UV-light flashes to classify cells as ON, OFF or ON-OFF retinal ganglion cells (RGCs) ( Figure S1; Table S1). We found that around 80% of the cells in the ganglion cell layer of young and adult retinas responded to light flashes with changes in fluorescence (Table S1), similar to the RGC percentages reported in previous studies [9,11,12]. In addition, over development we observed a decrease in the percentage of ON-OFF RGCs (28.03% at P13-14 to 20.84% in adult) (Table S1) [15].Second, we used light bars on a dark background drifting in 8 dir...

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Section: Potential Activity-dependent Mechanismsmentioning

confidence: 99%

Role for Visual Experience in the Development of Direction-Selective Circuits

Bos¹,

Gainer²,

Feller³

2017

Current Biology

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“…6 and Supplementary Fig. 2, and from a P30 C57BL/6 mouse for K0563 were prepared for E1088 and E2006 to selectively enhance cell outlines by using HRP-mediated precipitation of DAB (for preparation details 16 ) stained with osmium alone (E1088) or in conjunction with lead citrate (E2006). For K0563 a more conventional stain was used (same dataset as in 16 ).…”

Section: Sbemmentioning

confidence: 99%

“…Such a reconstruction was performed for the entire nervous system (302 neurons) of the nematode C. elegans 11 using serial-section electron microscopy. 4 Recently developed techniques for automated volume electron microscopy [12][13][14][15] enable the imaging of volumes large enough to contain more complex neural circuits 16 . However, extracting information about neuron morphology and circuit structure from such data poses two major challenges.…”

Section: Introductionmentioning

confidence: 99%

High-accuracy neurite reconstruction for high-throughput neuroanatomy

2011

Self Cite

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Neuroanatomic analysis depends on the reconstruction of complete cell shapes. Highthroughput reconstruction of neural circuits ("connectomics") using volume electron microscopy requires dense staining of all cells, where even experts make annotation errors.Currently, reconstruction rather than acquisition speed limits the determination of neural wiring diagrams. We present methods for the fast and reliable reconstruction of densely labeled datasets. Our approach, based on manually skeletonizing each neurite redundantly (multiple times) with a special visualization/annotation software tool (KNOSSOS), is ~50 times faster than volume labeling. Errors are detected and eliminated by a "redundantskeleton consensus procedure" (RESCOP), which uses a statistical model of how true neurite connectivity is transformed into annotation decisions. RESCOP also estimates the consensus skeletons' reliability. Focused re-annotation of difficult locations promises a rather steep increase of reliability as a function of the average skeleton redundancy and thus the nearly error-free analysis of large neuroanatomical datasets.

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“…By explicitly documenting synaptic connections using EM, the new approach of connectomics (7) now opens the possibility to study wiring variation more widely. However, existing connectomes (8,9) have yet to address this issue, and, so far, their accuracy could only be estimated insofar as the underlying circuit was incompletely known. Indeed, only for the nematode Caenorhabditis elegans, a model of determinate cell lineage and complement, is the complete synaptic network known (10,11).…”

mentioning

confidence: 99%

Synaptic circuits and their variations within different columns in the visual system of Drosophila

Takemura

Lǚ

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

261

379

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We reconstructed the synaptic circuits of seven columns in the second neuropil or medulla behind the fly's compound eye. These neurons embody some of the most stereotyped circuits in one of the most miniaturized of animal brains. The reconstructions allow us, for the first time to our knowledge, to study variations between circuits in the medulla's neighboring columns. This variation in the number of synapses and the types of their synaptic partners has previously been little addressed because methods that visualize multiple circuits have not resolved detailed connections, and existing connectomic studies, which can see such connections, have not so far examined multiple reconstructions of the same circuit. Here, we address the omission by comparing the circuits common to all seven columns to assess variation in their connection strengths and the resultant rates of several different and distinct types of connection error. Error rates reveal that, overall, <1% of contacts are not part of a consensus circuit, and we classify those contacts that supplement (E+) or are missing from it (E−). Autapses, in which the same cell is both presynaptic and postsynaptic at the same synapse, are occasionally seen; two cells in particular, Dm9 and Mi1, form ≥20-fold more autapses than do other neurons. These results delimit the accuracy of developmental events that establish and normally maintain synaptic circuits with such precision, and thereby address the operation of such circuits. They also establish a precedent for error rates that will be required in the new science of connectomics.neural circuits | stereotypy | biological error rates | reconstruction error rates

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Wiring specificity in the direction-selectivity circuit of the retina

Cited by 782 publications

References 51 publications

Role for Visual Experience in the Development of Direction-Selective Circuits

Role for Visual Experience in the Development of Direction-Selective Circuits

High-accuracy neurite reconstruction for high-throughput neuroanatomy

Synaptic circuits and their variations within different columns in the visual system of Drosophila

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