Capturing human category representations by sampling in deep feature spaces

Understanding how people represent categories is a core prob-lem in cognitive science. Decades of research have yieldeda variety of formal theories of categories, but validating themwith naturalistic stimuli is difficult. The challenge is that hu-man category representations cannot be directly observed andrunning informative experiments with naturalistic stimuli suchas images requires a workable representation of these stimuli.Deep neural networks have recently been successful in solvinga range of computer vision tasks and provide a way to com-pactly represent image features. Here, we introduce a methodto estimate the structure of human categories that combinesideas from cognitive science and machine learning, blendinghuman-based algorithms with state-of-the-art deep image gen-erators. We provide qualitative and quantitative results as aproof-of-concept for the method’s feasibility. Samples drawnfrom human distributions rival those from state-of-the-art gen-erative models in quality and outperform alternative methodsfor estimating the structure of human categories

Perspective on equitable translational studies and clinical support for an unbiased inclusion of the LGBTQIA2S+community.

Research regarding the mental health of the Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual, 2 Spirit (LGBTQIA2S+) community has been historically biased by individual and structural homophobia, biphobia, and transphobia, resulting in research that does not represent the best quality science. Furthermore, much of this research does not serve the best interests or priorities of LGBTQIA2S + communities, despite significant mental health disparities and great need for quality mental health research and treatments in these populations. Here, we will highlight how bias has resulted in missed opportunities for advancing understanding of mental health within LGBTQIA2S + communities. We cite up-to-date research on mental health disparities facing the LGBTQIA2S + community and targeted treatment strategies, as well as guidance from health care professionals. Importantly, research is discussed from both preclinical and clinical perspectives, providing common language and research priorities from a translational perspective. Given the rising tide of anti-transgender sentiment among certain political factions, we further emphasize and discuss the impact of historical and present day ciscentrism and structural transphobia in transgender mental health research, from both clinical and translational perspectives, with suggestions for future directions to improve the quality of this field. Finally, we address current best practices for treatment of mental health issues in this community. This approach provides an opportunity to dispel myths regarding the LGBTQIA2S + community as well as inform the scientific community of best practices to work with this community in an equitable manner. Thus, our approach ties preclinical and clinical research within the LGBTQIA2S + community

Centering the needs of transgender, non-binary, and gender-diverse populations in neuroendocrine models of gender-affirming hormone therapy

The majority of studies attempting to address the healthcare needs of the millions of transgender, non-binary, and/or gender diverse (TNG) individuals rely on human subjects, overlooking the benefits of translational research in animal models. Researchers have identified many ways in which gonadal steroid hormones regulate neuronal gene expression, connectivity, activity, and function across the brain to control behavior. However, these discoveries primarily benefit cisgender populations. Research into the effects of exogenous hormones such as estradiol, testosterone, and progesterone has direct translational benefit for TNG individuals on gender affirming hormone therapies (GAHT). Despite this potential, endocrinological healthcare for TNG individuals remains largely unimproved. Here, we outline important areas of translational research that could address the unique healthcare needs of TNG individuals on GAHT. We highlight key biomedical questions regarding GAHT that can be investigated using animal models. We discuss how contemporary research fails to address the needs of GAHT-users and identify equitable practices for cisgender scientists engaging with this work. We conclude that if necessary and important steps are taken to address these issues, translational research on GAHT will greatly benefit the healthcare outcomes of TNG people

Restoration of high-sensitivity and adapting vision with a cone opsin.

Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision

Determinants of synapse diversity revealed by super-resolution quantal transmission and active zone imaging.

Neural circuit function depends on the pattern of synaptic connections between neurons and the strength of those connections. Synaptic strength is determined by both postsynaptic sensitivity to neurotransmitter and the presynaptic probability of action potential evoked transmitter release (Pr). Whereas morphology and neurotransmitter receptor number indicate postsynaptic sensitivity, presynaptic indicators and the mechanism that sets Pr remain to be defined. To address this, we developed QuaSOR, a super-resolution method for determining Pr from quantal synaptic transmission imaging at hundreds of glutamatergic synapses at a time. We mapped the Pr onto super-resolution 3D molecular reconstructions of the presynaptic active zones (AZs) of the same synapses at the Drosophila larval neuromuscular junction (NMJ). We find that Pr varies greatly between synapses made by a single axon, quantify the contribution of key AZ proteins to Pr diversity and find that one of these, Complexin, suppresses spontaneous and evoked transmission differentially, thereby generating a spatial and quantitative mismatch between release modes. Transmission is thus regulated by the balance and nanoscale distribution of release-enhancing and suppressing presynaptic proteins to generate high signal-to-noise evoked transmission

Restoration of high-sensitivity and adapting vision with a cone opsin.

Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision