Biology subjects

Howlett, M. H. C.

Publications and source records attributed to Howlett, M. H. C..

3 recordsLinked to original sources

bioRxiv2025

Taking it slow: A positive feedback chloride current in cone photoreceptors supports slow motion detection

Photoreceptors gate and shape visual information. Since perception ultimately guides action, the way photoreceptors transform light into neural signals constrains an animals behavioural repertoire. Yet, the physiological role of the highly conserved calcium-dependent chloride current in cone photoreceptors has remained elusive. Whereas calcium-activated currents typically provide negative feedback, we identify a counter-intuitive positive feedback mechanism that enhances detection of slow motion. Using genetics, electrophysiology, and behavioural assays in zebrafish, we show that loss of this current exaggerates the biphasic character of cone impulse responses and diminishes their voltage response amplitude to low temporal frequencies (<1 Hz). These changes in photoreceptor properties translate to behaviour, reducing the gain of the optokinetic response to slow-moving stimuli. Mechanistically, the calcium-dependent chloride current acts as a positive feedback loop that sustains the photovoltage response and counteracts strong adaptation within the cone phototransduction cascade. This functional role is conserved across sensory modalities, as demonstrated by similar temporal integration and amplification observed in the odorant system.

neuroscience↗

bioRxiv2023

A Common Cause for Nystagmus in Different Congenital Stationary Night Blindness Mouse Models

In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, i.e., nystagmus. Given the distribution of mGluR6 and Cav1.4 in the retina as well as their clinical association with CSNB, we hypothesize that mGluR6-/- and Cav1.4-/- mutants show, like the Nyxnob mouse, oscillations that originate in the AII amacrine cells (AII ACs). Using eye movement and multi-electrode array (MEA) recordings of RGCs we show that the nystagmus as well as the underlying RGC oscillations are also present in mGluR6-/- and Cav1.4-/- mice. Yet, we find that the oscillations in the mGluR6-/- and Cav1.4-/- mutants slightly differ from each other and also from those of the Nyxnob mice. Moreover, each of the three mutations likely impacts the membrane potential of the AII ACs differently. Together our results indicate that nystagmus and oscillating RGCs are generalizable features associated with CSNB mutations localized at the photoreceptor-bipolar cell synapse.

neuroscience↗

bioRxiv2021

Enhancing the darkside: Asymmetric gain of cone photoreceptors underpins discrimination of visual scenes based on their skewness

Psychophysical data indicates humans can discriminate visual scenes based on their skewness - the ratio of dark and bright patches within a visual scene. It was also shown that on a phenomenological level this skew discrimination is described by the so-called Blackshot mechanism, which accentuates strong negative contrasts within a scene. Here we demonstrate that the underlying computation starts as early as the cone phototransduction cascade whose gain is higher for strong negative contrasts than for strong positive contrasts. We recorded from goldfish cone photoreceptors and found that the asymmetry in the phototransduction gain leads to higher amplitude of the responses to negatively than to positively skewed light stimuli. This asymmetry in the amplitude was present in the photocurrent, voltage response and cone synaptic output. These results highlight the importance of the early photoreceptor non-linearity for perception. Additionally, we found that stimulus skewness leads to a subtle change in photoreceptor kinetics. For negatively skewed stimuli, the cones impulse response functions peak later than for positively skewed stimulus. However, stimulus skewness does not affect the cones overall integration time.

neuroscience↗