Biology subjects

White, D. N.

Publications and source records attributed to White, D. N..

3 recordsLinked to original sources

bioRxiv2026

Synaptotagmin isoforms differentially regulate glutamate and GABA release in the lateral habenula

Neurotransmitter co-transmission contributes to diverse physiological processes throughout the mammalian brain, including sensory integration, motivational control, and social behaviors. Projections from the globus pallidus internus (GPi; the entopeduncular nucleus, EPN, in rodents) to the lateral habenula (LHb) are well-characterized by the co-transmission of both GABA and glutamate. These dual-release inputs modulate behavioral states in chronically learned helpless (cLH) rats, influencing both the onset and recovery of pathological phenotypes. Here, we employed confocal 3D reconstructions that confirmed the presence of both vesicular transporters VGAT and VGLUT2 in EPN axon terminals within the LHb. Further investigation revealed that GABA and glutamate are packaged in distinct vesicle populations within individual presynaptic terminals. Notably, the calcium (Ca{superscript 2}) sensors Synaptotagmin-2 (Syt2) and Synaptotagmin-3 (Syt3) are highly expressed in the EPN whereas expression of the canonical Ca{superscript 2} sensor, Synaptotagmin 1 (Syt1), is downregulated. Additionally, using confocal microscopy, we observed selective spatial correlations of Syt2 and VGLUT2 and between Syt3 and VGAT in LHb axon terminals. These observations strongly suggested that Syt2 serves as the predominant Ca{superscript 2} sensor for glutamatergic vesicle fusion, and Syt3 serves as the predominant Ca{superscript 2} sensor for GABAergic vesicle fusion in the LHb. To test this hypothesis, we employed targeted antisense oligonucleotide (ASO) knockdown of Syt2 and Syt3 in EPN neurons and measured LHb glutamatergic and GABAergic currents. Syt2 knockdown resulted in an increase in mEPSC frequency, amplitude, half-width and decay, suggesting increased glutamate vesicle release probability and increased glutamate vesicle packing. However, Syt2 knockdown had no influence on mIPSCs amplitude or frequency. On the other hand, Syt3 knockdown had no apparent effect on glutamate release but caused an increase in mIPSC frequency suggesting increased quantal release probability of GABA. Together, these findings identify a molecular mechanism by which synaptotagmin isoforms govern differential glutamate and GABA release at EPN dual-transmitter terminals in the LHb. These results provide evidence for presynaptic mechanisms regulating excitatory-inhibitory balance within this brain structure and importantly provide molecular targets for pharmacological intervention.

neuroscience↗

bioRxiv2024

Sources of uncertainty in human stereo-depth perception in natural images and scenes

2Stimulus variability--a form of nuisance variability--is a primary source of perceptual uncertainty in every-day natural tasks. How do different properties of natural images and scenes contribute to this uncertainty? Using binocular disparity as a model system, we report a systematic investigation of how various forms of natural stimulus variability impact performance in a stereo-depth discrimination task. With stimuli sampled from a stereo-image database of real-world scenes having pixel-by-pixel ground-truth distance data, three human observers completed two closely related double-pass psychophysical experiments. In the two experiments, each human observer responded twice to ten thousand unique trials, in which twenty thousand unique stimuli were presented. New analytical methods reveal, from this data, the specific and nearly dissociable effects of two distinct sources of natural stimulus variability--variation in luminance-contrast patterns and variation in local-depth structure--on discrimination performance, as well as the relative importance of stimulus-driven-variability and internal-noise in determining performance limits. Between-observer analyses show that both stimulus-driven sources of uncertainty are responsible for a large proportion of total variance, have strikingly similar effects on different people, and--surprisingly--make stimulus-by-stimulus responses more predictable (not less). The consistency across observers raises the intriguing prospect that image-computable models can make reasonably accurate performance predictions in natural viewing. Overall, the findings provide a rich picture of stimulus factors that contribute to human perceptual performance in natural scenes. The approach should have broad application to other animal models and other sensory-perceptual tasks with natural or naturalistic stimuli. 1 SignificanceLinking properties of the external world, and of sensory stimuli, to how neurons and animals respond has proven an important approach to understanding how the brain works. Much is known about how nervous systems respond to simple stimuli. Less is known about how systems respond during real-world viewing. Using data from two human stereo-depth discrimination experiments, we develop a new approach that reveals how distinct features of natural scenes and images contribute to perceptual performance. Results show that stimulus-by-stimulus variation has highly consistent effects on different people. The approach should have broad application to other animal models and other sensory-perceptual tasks.

neuroscience↗

bioRxiv2020

Natural image statistics at depth edges modulate perceptual stability

Binocular fusion relies on matching points in the two eyes that correspond to the same physical feature in the world. However, not all world features are binocularly visible. In particular, at depth edges parts of a scene are often visible to only one eye (so-called half occlusions). Accurate detection of these monocularly visible regions is likely to be important for stable visual perception. If monocular regions are not detected as such, the visual system may attempt to binocularly fuse non-corresponding points, which can result in unstable percepts. We investigated the hypothesis that the visual system capitalizes upon statistical regularities associated with depth edges in natural scenes to aid binocular fusion and facilitate perceptual stability. By sampling from a large set of stereoscopic natural image patches, we found evidence that monocularly visible regions near depth edges in natural scenes tend to have features more visually similar to the adjacent binocularly visible background region than to the adjacent binocularly visible foreground. The generality of these results was supported by a parametric study of three-dimensional (3D) viewing geometry in simulated environments. In two perceptual experiments, we examined if this statistical regularity may be leveraged by the visual system. The results show that perception tended to be more stable when the visual properties of the depth edge were statistically more likely. Exploiting regularities in natural environments may allow the visual system to facilitate fusion and perceptual stability of natural scenes when both binocular and monocular regions are visible. PrecisWe report an analysis of natural scenes and two perceptual studies aimed at understanding how the visual statistics of depth edges impact perceptual stability. Our results suggest that the visual system exploits natural scene regularities to aid binocular fusion and facilitate perceptual stability.

neuroscience↗