First-order visual interneurons distribute distinct contrast and luminance information across ON and OFF pathways to achieve stable behavior

The accurate processing of contrast is the basis for all visually guided behaviors. Visual scenes with rapidly changing illumination challenge contrast computation, because adaptation is not fast enough to compensate for such changes. Yet, human perception of contrast is stable even when the visual environment is quickly changing. The fruit fly Drosophila also shows nearly luminance invariant behavior for both ON and OFF stimuli. To achieve this, first-order interneurons L1, L2 and L3 all encode contrast and luminance differently, and distribute information across both ON and OFF contrast-selective pathways. Behavioral responses to both ON and OFF stimuli rely on a luminance-based correction provided by L1 and L3, wherein L1 supports contrast computation linearly, and L3 non-linearly amplifies dim stimuli. Therefore, L1, L2 and L3 are not distinct inputs to ON and OFF pathways but the lamina serves as a separate processing layer that distributes distinct luminance and contrast information across ON and OFF pathways to support behavioral performance in varying conditions.

Synergy of color and motion vision for detecting approaching objects in Drosophila

Color and motion are used by many species to identify salient moving objects. They are processed largely independently, but color contributes to motion processing in humans, for example, enabling moving colored objects to be detected when their luminance matches the background. Here, we demonstrate an unexpected, additional contribution of color to motion vision in Drosophila. We show that behavioral ON-motion responses are more sensitive to UV than for OFF-motion, and we identify cellular pathways connecting UV-sensitive R7 photoreceptors to ON and OFF-motion-sensitive T4 and T5 cells, using neurogenetics and calcium imaging. Remarkably, the synergy of color and motion vision enhances the detection of approaching UV discs, but not green discs with the same chromatic contrast, and we show how this generalizes for visual systems with ON and OFF pathways. Our results provide a computational and circuit basis for how color enhances motion vision to favor the detection of saliently colored objects.

Scene statistics and noise determine the relative arrangement of receptive field mosaics

Many sensory systems utilize parallel ON and OFF pathways that signal stimulus increments and decrements, respectively. These pathways consist of ensembles or grids of ON and OFF detectors spanning sensory space. Yet, encoding by opponent pathways raises a question: How should grids of ON and OFF detectors be arranged to optimally encode natural stimuli? We investigated this question using a model of the retina guided by efficient coding theory. Specifically, we optimized spatial receptive fields and contrast response functions to encode natural images given noise and constrained firing rates. We find that the optimal arrangement of ON and OFF receptive fields exhibits a transition between aligned and antialigned grids. The preferred phase depends on detector noise and the statistical structure of the natural stimuli. These results reveal that noise and stimulus statistics produce qualitative shifts in neural coding strategies and provide theoretical predictions for the configuration of opponent pathways in the nervous system.

Edge-strand of BepA interacts with immature LptD on the β-barrel assembly machine to direct it to on- and off-pathways

The outer membrane (OM) of gram-negative bacteria functions as a selective permeability barrier. Escherichia coli periplasmic Zn-metallopeptidase BepA contributes to the maintenance of OM integrity through its involvement in the biogenesis and degradation of LptD, a β-barrel protein component of the lipopolysaccharide translocon. BepA either promotes the maturation of LptD when it is on the normal assembly pathway (on-pathway) or degrades it when its assembly is compromised (off-pathway). BepA performs these functions probably on the β‐barrel assembly machinery (BAM) complex. However, how BepA recognizes and directs an immature LptD to different pathways remains unclear. Here, we explored the interactions among BepA, LptD, and the BAM complex. We found that the interaction of the BepA edge-strand located adjacent to the active site with LptD was crucial not only for proteolysis but also, unexpectedly, for assembly promotion of LptD. Site-directed crosslinking analyses indicated that the unstructured N-terminal half of the β-barrel-forming domain of an immature LptD contacts with the BepA edge-strand. Furthermore, the C-terminal region of the β-barrel-forming domain of the BepA-bound LptD intermediate interacted with a 'seam' strand of BamA, suggesting that BepA recognized LptD assembling on the BAM complex. Our findings provide important insights into the functional mechanism of BepA.

Non-preferred contrast responses in the Drosophila motion pathways reveal a receptive field structure that explains a common visual illusion

Diverse sensory systems, from audition to thermosensation, feature a separation of inputs into ON (increments) and OFF (decrements) signals. In the Drosophila visual system, separate ON and OFF pathways compute the direction of motion, yet anatomical and functional studies have identified some crosstalk between these channels. We used this well-studied circuit to ask whether the motion computation depends on ON-OFF pathway crosstalk. Using whole-cell electrophysiology we recorded visual responses of T4 (ON) and T5 (OFF) cells and discovered that both cell types are also directionally selective in response to non-preferred contrast motion. We mapped T4s' and T5s' composite ON-OFF receptive fields and found they share a similar spatiotemporal structure. We fit a biophysical model to these receptive fields that accurately predicts directionally selective T4 and T5 responses to both ON and OFF moving stimuli. This model also provides a detailed mechanistic explanation for the directional-preference inversion in response to a prominent visual illusion, a result we corroborate with electrophysiological recordings and behavioral responses of flying flies.

In vivo Morphometry of Inner Plexiform Layer (IPL) Stratification in the Human Retina With Visible Light Optical Coherence Tomography

From the bipolar cells to higher brain visual centers, signals in the vertebrate visual system are transmitted along parallel on and off pathways. These two pathways are spatially segregated along the depth axis of the retina. Yet, to our knowledge, there is no way to directly assess this anatomical stratification in vivo. Here, employing ultrahigh resolution visible light Optical Coherence Tomography (OCT) imaging in humans, we report a stereotyped reflectivity pattern of the inner plexiform layer (IPL) that parallels IPL stratification. We characterize the topography of this reflectivity pattern non-invasively in a cohort of normal, young adult human subjects. This proposed correlate of IPL stratification is accessible through non-invasive ocular imaging in living humans. Topographic variations should be carefully considered when designing studies in development or diseases of the visual system.

Edge strand of Escherichia coli BepA interacts with immature LptD on the β-barrel assembly machine to direct it to on- and off-pathways

The outer membrane (OM) of gram-negative bacteria is crucial for maintenance of cell viability as it functions as a selective permeability barrier. Escherichia coli periplasmic Zn-metallopeptidase BepA contributes to the maintenance of OM integrity through its involvement in the biogenesis and degradation of an essential OM protein, LptD, a β-barrel component of the lipopolysaccharide translocon. We have previously shown that BepA either promotes the maturation of LptD when it is on the normal assembly pathway (on-pathway) or degrades it when its assembly is compromised (off-pathway). BepA performs these functions possibly on the β‐barrel assembly machinery (BAM) complex. However, the mechanistic details of how BepA recognizes and directs the LptD assembly intermediates to different pathways remains unclear. Here, we performed site-directed mutagenesis and crosslinking experiments to explore the interactions among BepA, LptD, and the BAM complex. We found that the interaction of the BepA edge strand located adjacent to the active site with LptD was crucial not only for proteolysis but also for assembly promotion of LptD. Site-directed crosslinking analysis indicated that the unstructured N-terminal half of the β-barrel-forming domain of an LptD assembly intermediate directly contacts with the BepA edge strand. Furthermore, the C-terminal region of the β-barrel-forming domain of the BepA-bound LptD intermediate interacted with a 'seam' strand of BamA, suggesting that BepA recognized LptD assembling on the BAM complex. Our findings provide important insights into the involvement of BepA in the maintenance of OM structure and function, which can be helpful in developing OM-targeted novel drugs.

The optimal spatial arrangement of ON and OFF receptive fields

Many sensory systems utilize parallel ON and OFF pathways that signal stimulus increments and decrements, respectively. These pathways consist of ensembles or grids of ON and OFF detectors spanning sensory space. Yet encoding by opponent pathways raises a question: How should grids of ON and OFF detectors be arranged to optimally encode natural stimuli? We investigated this question using a model of the retina guided by efficient coding theory. Specifically, we optimized spatial receptive fields and contrast response functions to encode natural images given noise and constrained firing rates. We find that the optimal arrangement of ON and OFF receptive fields exhibits a second-order phase transition between aligned and anti-aligned grids. The preferred phase depends on detector noise and the statistical structure of the natural stimuli. These results reveal that noise and stimulus statistics produce qualitative shifts in neural coding strategies and provide novel theoretical predictions for the configuration of opponent pathways in the nervous system.

Retinal circuits driving a non-image forming visual behavior

Outer retinal circuits that drive non-image forming vision in mammals are unknown. Rods and cones signal light increments and decrements to the brain through the ON and OFF pathways, respectively. Although their contribution to image-forming vision is known, the contributions of the ON and OFF pathway to the pupillary light response (PLR), a non-image forming behavior, are unexplored. Here we use genetically modified mouse lines, to comprehensively define the outer retinal circuits driving the PLR. The OFF pathway, which mirrors the ON pathway in image-forming vision, plays no role in the PLR. We found that rods use the primary rod pathway to drive the PLR at scotopic light levels. At photopic light levels, the primary and secondary rod pathways drive normal PLR. Importantly, we find that cones are unable to compensate for rods. Thus, retinal circuit dynamics allow rods to drive the PLR across a wide range of light intensities.

Modelling Drosophila motion vision pathways for decoding the direction of translating objects against cluttered moving backgrounds

Decoding the direction of translating objects in front of cluttered moving backgrounds, accurately and efficiently, is still a challenging problem. In nature, lightweight and low-powered flying insects apply motion vision to detect a moving target in highly variable environments during flight, which are excellent paradigms to learn motion perception strategies. This paper investigates the fruit fly Drosophila motion vision pathways and presents computational modelling based on cutting-edge physiological researches. The proposed visual system model features bio-plausible ON and OFF pathways, wide-field horizontal-sensitive (HS) and vertical-sensitive (VS) systems. The main contributions of this research are on two aspects: (1) the proposed model articulates the forming of both direction-selective and direction-opponent responses, revealed as principal features of motion perception neural circuits, in a feed-forward manner; (2) it also shows robust direction selectivity to translating objects in front of cluttered moving backgrounds, via the modelling of spatiotemporal dynamics including combination of motion pre-filtering mechanisms and ensembles of local correlators inside both the ON and OFF pathways, which works effectively to suppress irrelevant background motion or distractors, and to improve the dynamic response. Accordingly, the direction of translating objects is decoded as global responses of both the HS and VS systems with positive or negative output indicating preferred-direction or null-direction translation. The experiments have verified the effectiveness of the proposed neural system model, and demonstrated its responsive preference to faster-moving, higher-contrast and larger-size targets embedded in cluttered moving backgrounds.