Biology subjects

Helmbrecht, T. O.

Publications and source records attributed to Helmbrecht, T. O..

3 recordsLinked to original sources

bioRxiv2020

Molecular classification of zebrafish retinal ganglion cells links genes to cell types to behavior

Retinal ganglion cells (RGCs) form an array of feature detectors, which convey visual information to central brain regions. Characterizing RGC diversity is required to understand the logic of the underlying functional segregation. Using single-cell transcriptomics, we systematically classified RGCs in adult and larval zebrafish, thereby identifying marker genes for at least 33 stable and transient cell types. We used this dataset to engineer transgenic driver lines, enabling experimental access to specific RGC types. Strikingly, expression of one or few transcription factors often predicts dendrite morphologies and axonal projections to specific tectal layers and extratectal targets. In vivo calcium imaging revealed that molecularly defined RGCs exhibit highly specific functional tuning. Finally, chemogenetic ablation of eomesa+ RGCs, which comprise melanopsin-expressing types with projections to a small subset of central targets, selectively impaired phototaxis. Together, our study establishes a framework for systematically studying the functional architecture of the visual system.

neuroscience↗

bioRxiv2019

Neuronal circuitry for stimulus selection in the visual system

Visual objects naturally compete for the brains attention, and selecting just one of them for a behavioural response is often crucial for the animals survival1. The neural correlate of such stimulus prioritisation might take the form of a saliency map by which responses to one target are enhanced relative to distractors in other parts of the visual field2. Single-cell responses consistent with this type of computation have been observed in the tectum of primates, birds, turtles and lamprey2-7. However, the exact circuit implementation has remained unclear. Here we investigated the underlying neuronal mechanism presenting larval zebrafish with two simultaneous looming stimuli, each of which was able to trigger directed escapes on their own. Behaviour tracking revealed that the fish respond to these competing stimuli predominantly with a winner-take-all strategy. Using brain-wide functional recordings, we discovered neurons in the tectum whose responses to the target stimulus were non-linearly modulated by the saliency of the distractor. When the two stimuli were presented monocularly in different positions of the visual field, stimulus selection was already apparent in the activity of retinal ganglion cell axons, a likely consequence of antagonistic mechanisms operating outside the classical receptive field8,9. When the two stimuli were presented binocularly, i.e., on opposite sides of the fish, our analysis indicates that a loop involving excitatory and inhibitory neurons in the nucleus isthmi (NI) and the tectum weighed stimulus saliencies across hemispheres. Consistent with focal enhancement and global suppression, glutamatergic NI cells branch locally in the tectum, whereas GABAergic NI cells project broadly across both tectal hemispheres. Moreover, holographic optogenetic stimulation confirmed that glutamatergic NI neurons can modulate visual responses in the tectum. Together, our study shows, for the first time, context-dependent contributions of retinotectal and isthmotectal circuits to the computation of the visual saliency map, a prerequisite for stimulus-driven, bottom-up attention.

neuroscience↗

bioRxiv2017

Detection of whole-field luminance changes by superficial interneurons in the zebrafish tectum

The superficial interneurons, SINs, of the zebrafish tectum, also known as tectal horizontal cells, have been implicated in a range of behavioral responses to visual cues, including prey capture and looming-evoked escape. However, there is limited information on their tuning properties, synaptic connectivity and molecular diversity. We have begun to close this gap in our knowledge by performing functional GCaMP6 imaging and electrophysiological recordings of SIN responses to simplified stimuli. We found that a large subset of the SINs strongly responded to luminance changes, with a preference for OFF steps. Although SINs were generally tuned to any dark-light, or light-dark, transition, they were often most sensitive to a narrow range of luminance steps. Tuning properties did not vary with the position of the SIN cell body along the depth of the tectal neuropil or with the orientation of the cell neurites within the neuropil. Receptive field (RF) mapping revealed that SINs sample over large areas of the visual field (greater than 20 degrees, typically 50 degrees). RFs of individual SINs were sometimes spatially incoherent, indicating that SINs may receive sparse inputs from multiple RGCs scattered widely over the retina. Lastly, we found that, while most SINs express GABAergic markers, as reported before, a substantial minority express a vesicular glutamate transporter. We propose that the role of the SINs is more complex than previously reported, and provide evidence that at least one SIN subtype could function as a multi-purpose circuit element for signaling changes in ambient luminance for subsequent processing in the tectum.

neuroscience↗