Early Vision: Where (Some of) the Magic Happens

SummaryA recent study provides new insights into how the very different response characteristics of the main visual pathways from the eye to the brain may directly result from the presence or absence of a ‘spike trigger-zone’ in retinal bipolar cells

Visual neuroscience: a retinal ganglion cell to report image focus?

A recent study describes a mouse neuron projecting from the retina to the brain that exhibits exquisitely high sensitivity to high spatial frequency patterns presented over an unusually large receptive field: could this cell be a (de)focus detector

In situ characterisation and manipulation of biological systems with Chi.Bio

The precision and repeatability of in vivo biological studies is predicated upon methods for isolating a targeted subsystem from external sources of noise and variability. However, in many experimental frameworks, this is made challenging by nonstatic environments during host cell growth, as well as variability introduced by manual sampling and measurement protocols. To address these challenges, we developed Chi.Bio, a parallelised open-source platform that represents a new experimental paradigm in which all measurement and control actions can be applied to a bulk culture in situ. In addition to continuous-culturing capabilities, it incorporates tunable light outputs, spectrometry, and advanced automation features. We demonstrate its application to studies of cell growth and biofilm formation, automated in silico control of optogenetic systems, and readout of multiple orthogonal fluorescent proteins in situ. By integrating precise measurement and actuation hardware into a single low-cost platform, Chi.Bio facilitates novel experimental methods for synthetic, systems, and evolutionary biology and broadens access to cutting-edge research capabilities

Fovea-like photoreceptor specializations underlie single UV cone driven prey-capture behavior in zebrafish

In the eye, the function of same-type photoreceptors must be regionally adjusted to process a highly asymmetrical natural visual world. Here, we show that UV cones in the larval zebrafish area temporalis are specifically tuned for UV-bright prey capture in their upper frontal visual field, which may use the signal from a single cone at a time. For this, UV-photon detection probability is regionally boosted more than 10-fold. Next, in vivo two-photon imaging, transcriptomics, and computational modeling reveal that these cones use an elevated baseline of synaptic calcium to facilitate the encoding of bright objects, which in turn results from expressional tuning of phototransduction genes. Moreover, the light-driven synaptic calcium signal is regionally slowed by interactions with horizontal cells and later accentuated at the level of glutamate release driving retinal networks. These regional differences tally with variations between peripheral and foveal cones in primates and hint at a common mechanistic origin

Leveraging open hardware to alleviate the burden of COVID-19 on global health systems.

With the current rapid spread of COVID-19, global health systems are increasingly overburdened by the sheer number of people that need diagnosis, isolation and treatment. Shortcomings are evident across the board, from staffing, facilities for rapid and reliable testing to availability of hospital beds and key medical-grade equipment. The scale and breadth of the problem calls for an equally substantive response not only from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilities and knowledge to meaningfully contribute to a consolidated global response. Here, we summarise community-driven approaches based on Free and Open Source scientific and medical Hardware (FOSH) as well as personal protective equipment (PPE) currently being developed and deployed to support the global response for COVID-19 prevention, patient treatment and diagnostics

Imaging Ca²+ dynamics in cone photoreceptor axon terminals of the mouse retina

Retinal cone photoreceptors (cones) serve daylight vision and are the basis of color discrimination. They are subject to degeneration, often leading to blindness in many retinal diseases. Calcium (Ca2+), a key second messenger in photoreceptor signaling and metabolism, has been proposed to be indirectly linked with photoreceptor degeneration in various animal models. Systematically studying these aspects of cone physiology and pathophysiology has been hampered by the difficulties of electrically recording from these small cells, in particular in the mouse where the retina is dominated by rod photoreceptors. To circumvent this issue, we established a two-photon Ca2+ imaging protocol using a transgenic mouse line that expresses the genetically encoded Ca²+ biosensor TN-XL exclusively in cones and can be crossbred with mouse models for photoreceptor degeneration. The protocol described here involves preparing vertical sections (“slices”) of retinas from mice and optical imaging of light stimulus-evoked changes in cone Ca²+ level. The protocol also allows “in-slice measurement” of absolute Ca²+ concentrations; as the recordings can be followed by calibration. This protocol enables studies into functional cone properties and is expected to contribute to the understanding of cone Ca²+ signaling as well as the potential involvement of Ca²+ in photoreceptor death and retinal degeneration

GABAA_A Receptors Containing the α\alpha2 Subunit Are Critical for Direction-Selective Inhibition in the Retina

Far from being a simple sensor, the retina actively participates in processing visual signals. One of the best understood aspects of this processing is the detection of motion direction. Direction-selective (DS) retinal circuits include several subtypes of ganglion cells (GCs) and inhibitory interneurons, such as starburst amacrine cells (SACs). Recent studies demonstrated a surprising complexity in the arrangement of synapses in the DS circuit, i.e. between SACs and DS ganglion cells. Thus, to fully understand retinal DS mechanisms, detailed knowledge of all synaptic elements involved, particularly the nature and localization of neurotransmitter receptors, is needed. Since inhibition from SACs onto DSGCs is crucial for generating retinal direction selectivity, we investigate here the nature of the GABA receptors mediating this interaction. We found that in the inner plexiform layer (IPL) of mouse and rabbit retina, GABA$_A$ receptor subunit $\alpha$2 (GABA$_A$R $\alpha$2) aggregated in synaptic clusters along two bands overlapping the dendritic plexuses of both ON and OFF SACs. On distal dendrites of individually labeled SACs in rabbit, GABA$_A$R $\alpha$2 was aligned with the majority of varicosities, the cell's output structures, and found postsynaptically on DSGC dendrites, both in the ON and OFF portion of the IPL. In GABA$_A$R $\alpha$2 knock-out (KO) mice, light responses of retinal GCs recorded with two-photon calcium imaging revealed a significant impairment of DS responses compared to their wild-type littermates. We observed a dramatic drop in the proportion of cells exhibiting DS phenotype in both the ON and ON-OFF populations, which strongly supports our anatomical findings that $\alpha$2-containing GABA$_A$Rs are critical for mediating retinal DS inhibition. Our study reveals for the first time, to the best of our knowledge, the precise functional localization of a specific receptor subunit in the retinal DS circuit

Colourfulness as a possible measure of object proximity in the larval zebrafish brain

The encoding of light increments and decrements by separate On- and Off- systems is a fundamental ingredient of vision, which supports edge detection and makes efficient use of the limited dynamic range of visual neurons. Theory predicts that the neural representation of On- and Off-signals should be balanced, including across an animal’s visible spectrum. Here we find that larval zebrafish violate this textbook expectation: in the zebrafish brain, UV-stimulation near exclusively gives On-responses, blue/green stimulation mostly Off-responses, and red-light alone elicits approximately balanced On- and Off-responses (see also references2, 3, 4). We link these findings to zebrafish visual ecology, and suggest that the observed spectral tuning boosts the encoding of object ‘colourfulness’, which correlates with object proximity in their underwater world