Zhuoyi Song

Stochastic, adaptive sampling of information by microvilli in fly photoreceptors.

Summary Background In fly photoreceptors, light is focused onto a photosensitive waveguide, the rhabdomere, consisting of tens of thousands of microvilli. Each microvillus is capable of generating elementary responses, quantum bumps, in response to single photons using a stochastically operating phototransduction cascade. Whereas much is known about the cascade reactions, less is known about how the concerted action of the microvilli population encodes light changes into neural information and how the ultrastructure and biochemical machinery of photoreceptors of flies and other insects evolved in relation to the information sampling and processing they perform. Results We generated biophysically realistic fly photoreceptor models, which accurately simulate the encoding of visual information. By comparing stochastic simulations with single cell recordings from Drosophila photoreceptors, we show how adaptive sampling by 30,000 microvilli captures the temporal structure of natural contrast changes. Following each bump, individual microvilli are rendered briefly (∼100–200 ms) refractory, thereby reducing quantum efficiency with increasing intensity. The refractory period opposes saturation, dynamically and stochastically adjusting availability of microvilli (bump production rate: sample rate), whereas intracellular calcium and voltage adapt bump amplitude and waveform (sample size). These adapting sampling principles result in robust encoding of natural light changes, which both approximates perceptual contrast constancy and enhances novel events under different light conditions, and predict information processing across a range of species with different visual ecologies. Conclusions These results clarify why fly photoreceptors are structured the way they are and function as they do, linking sensory information to sensory evolution and revealing benefits of stochasticity for neural information processing.

Refractory Sampling Links Efficiency and Costs of Sensory Encoding to Stimulus Statistics

Sensory neurons integrate information about the world, adapting their sampling to its changes. However, little is understood mechanistically how this primary encoding process, which ultimately limits perception, depends upon stimulus statistics. Here, we analyze this open question systematically by using intracellular recordings from fly (Drosophila melanogaster and Coenosia attenuata) photoreceptors and corresponding stochastic simulations from biophysically realistic photoreceptor models. Recordings show that photoreceptors can sample more information from naturalistic light intensity time series (NS) than from Gaussian white-noise (GWN), shuffled-NS or Gaussian-1/f stimuli; integrating larger responses with higher signal-to-noise ratio and encoding efficiency to large bursty contrast changes. Simulations reveal how a photoreceptors information capture depends critically upon the stochastic refractoriness of its 30,000 sampling units (microvilli). In daylight, refractoriness sacrifices sensitivity to enhance intensity changes in neural image representations, with more and faster microvilli improving encoding. But for GWN and other stimuli, which lack longer dark contrasts of real-world intensity changes that reduce microvilli refractoriness, these performance gains are submaximal and energetically costly. These results provide mechanistic reasons why information sampling is more efficient for natural/naturalistic stimulation and novel insight into the operation, design, and evolution of signaling and code in sensory neurons.

Biophysical Modeling of a Drosophila Photoreceptor

It remains unclear how visual information is co-processed by different layers of neurons in the retina. In particular, relatively little is known how retina translates vast environmental light changes into neural responses of limited range. We began examining this question in a bottom-up way in a relatively simple fly eye. To gain understanding of how complex bio-molecular interactions govern the conversion of light input into voltage output (phototransduction), we are building a biophysical model of the Drosophila R1-R6 photoreceptor. Our model, which relates molecular dynamics of the underlying biochemical reactions to external light input, attempts to capture the molecular dynamics of phototransduction gain control in a quantitative way.

Random Photon Absorption Model Elucidates How Early Gain Control in Fly Photoreceptors Arises from Quantal Sampling

Many diurnal photoreceptors encode vast real-world light changes effectively, but how this performance originates from photon sampling is unclear. A 4-module biophysically-realistic fly photoreceptor model, in which information capture is limited by the number of its sampling units (microvilli) and their photon-hit recovery time (refractoriness), can accurately simulate real recordings and their information content. However, sublinear summation in quantum bump production (quantum-gain-nonlinearity) may also cause adaptation by reducing the bump/photon gain when multiple photons hit the same microvillus simultaneously. Here, we use a Random Photon Absorption Model (RandPAM), which is the 1st module of the 4-module fly photoreceptor model, to quantify the contribution of quantum-gain-nonlinearity in light adaptation. We show how quantum-gain-nonlinearity already results from photon sampling alone. In the extreme case, when two or more simultaneous photon-hits reduce to a single sublinear value, quantum-gain-nonlinearity is preset before the phototransduction reactions adapt the quantum bump waveform. However, the contribution of quantum-gain-nonlinearity in light adaptation depends upon the likelihood of multi-photon-hits, which is strictly determined by the number of microvilli and light intensity. Specifically, its contribution to light-adaptation is marginal (≤ 1%) in fly photoreceptors with many thousands of microvilli, because the probability of simultaneous multi-photon-hits on any one microvillus is low even during daylight conditions. However, in cells with fewer sampling units, the impact of quantum-gain-nonlinearity increases with brightening light.

Microsaccadic information sampling provides Drosophila hyperacute vision

Small fly eyes should not see fine image details. Because flies exhibit saccadic visual behaviors and their compound eyes have relatively few ommatidia (sampling points), their photoreceptors would be expected to generate blurry and coarse retinal images of the world. Here we demonstrate that Drosophila see the world far better than predicted from the classic theories. By using electrophysiological, optical and behavioral assays, we found that R1-R6 photoreceptors’ encoding capacity in time is maximized to fast high-contrast bursts, which resemble their light input during saccadic behaviors. Whilst over space, R1-R6s resolve moving objects at saccadic speeds beyond the predicted motion-blur-limit. Our results show how refractory phototransduction and rapid photomechanical photoreceptor contractions jointly sharpen retinal images in space-time, enabling hyperacute vision, and explain how such microsaccadic information sampling exceeds the compound eyes’ optical limits.

How a fly photoreceptor samples light information in time

A photoreceptors information capture is constrained by the structure and function of its light‐sensitive parts. Specifically, in a fly photoreceptor, this limit is set by the number of its photon sampling units (microvilli), constituting its light sensor (the rhabdomere), and the speed and recoverability of their phototransduction reactions. In this review, using an insightful constructionist viewpoint of a fly photoreceptor being an ‘imperfect’ photon counting machine, we explain how these constraints give rise to adaptive quantal information sampling in time, which maximises information in responses to salient light changes while antialiasing visual signals. Interestingly, such sampling innately determines also why photoreceptors extract more information, and more economically, from naturalistic light contrast changes than Gaussian white‐noise stimuli, and we explicate why this is so. Our main message is that stochasticity in quantal information sampling is less noise and more processing, representing an ‘evolutionary adaptation’ to generate a reliable neural estimate of the variable world.

A biomimetic fly photoreceptor model elucidates how stochastic adaptive quantal sampling provides a large dynamic range

Light intensities (photons s–1 μm–2) in a natural scene vary over several orders of magnitude from shady woods to direct sunlight. A major challenge facing the visual system is how to map such a large dynamic input range into its limited output range, so that a signal is neither buried in noise in darkness nor saturated in brightness. A fly photoreceptor has achieved such a large dynamic range; it can encode intensity changes from single to billions of photons, outperforming man‐made light sensors. This performance requires powerful light adaptation, the neural implementation of which has only become clear recently. A computational fly photoreceptor model, which mimics the real phototransduction processes, has elucidated how light adaptation happens dynamically through stochastic adaptive quantal information sampling. A Drosophila R1–R6 photoreceptors light sensor, the rhabdomere, has 30,000 microvilli, each of which stochastically samples incoming photons. Each microvillus employs a full G‐protein‐coupled receptor signalling pathway to adaptively transduce photons into quantum bumps (QBs, or samples). QBs then sum the macroscopic photoreceptor responses, governed by four quantal sampling factors (limitations): (i) the number of photon sampling units in the cell structure (microvilli), (ii) sample size (QB waveform), (iii) latency distribution (time delay between photon arrival and emergence of a QB), and (iv) refractory period distribution (time for a microvillus to recover after a QB). Here, we review how these factors jointly orchestrate light adaptation over a large dynamic range.

Microsaccadic sampling of moving image information provides Drosophila hyperacute vision

Small fly eyes should not see fine image details. Because flies exhibit saccadic visual behaviors and their compound eyes have relatively few ommatidia (sampling points), their photoreceptors would be expected to generate blurry and coarse retinal images of the world. Here we demonstrate that Drosophila see the world far better than predicted from the classic theories. By using electrophysiological, optical and behavioral assays, we found that R1-R6 photoreceptors’ encoding capacity in time is maximized to fast high-contrast bursts, which resemble their light input during saccadic behaviors. Whilst over space, R1-R6s resolve moving objects at saccadic speeds beyond the predicted motion-blur-limit. Our results show how refractory phototransduction and rapid photomechanical photoreceptor contractions jointly sharpen retinal images of moving objects in space-time, enabling hyperacute vision, and explain how such microsaccadic information sampling exceeds the compound eyes’ optical limits. These discoveries elucidate how acuity depends upon photoreceptor function and eye movements.

Shining new light into the workings of photoreceptors and visual interneurons

Vision starts at the retina. Photoreceptors sample and process visual information and redistribute it synaptically over a rich array of retinal channels, enabling animals to see the world consistently over vastly varying light conditions. Owing to the recent advances in molecular biology, genetics, powerful recording methods and computers, much has been learned about how the phototransduction and visual interneurons work, shining new light into the design principles, mechanisms and computations that underlie early vision. To encourage systems perspective discussions between neurobiologists and engineers about this topic, covering multiple scales (from molecules to circuits) and various animal models (from insects to vertebrates), we organised the ‘1st interdisciplinary UK phototransduction and synaptic transmission workshop’ at the University of Sheffield in September 2016. This special issue is a collection of review papers by the workshop speakers, highlighting the systems perspective in studying early vision.

Modeling elucidates how refractory period can provide profound nonlinear gain control to graded potential neurons

Refractory period (RP) plays a central role in neural signaling. Because it limits an excitable membranes recovery time from a previous excitation, it can restrict information transmission. Classically, RP means the recovery time from an action potential (spike), and its impact to encoding has been mostly studied in spiking neurons. However, many sensory neurons do not communicate with spikes but convey information by graded potential changes. In these systems, RP can arise as an intrinsic property of their quantal micro/nanodomain sampling events, as recently revealed for quantum bumps (single photon responses) in microvillar photoreceptors. Whilst RP is directly unobservable and hard to measure, masked by the graded macroscopic response that integrates numerous quantal events, modeling can uncover its role in encoding. Here, we investigate computationally how RP can affect encoding of graded neural responses. Simulations in a simple stochastic process model for a fly photoreceptor elucidate how RP can profoundly contribute to nonlinear gain control to achieve a large dynamic range.