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Kim, A. J.

Publications and source records attributed to Kim, A. J..

21 records · Page 2Linked to original sources

Neural Correlates of Value-Driven Spatial Attention

Reward learning has been shown to habitually guide spatial attention to regions of a scene. However, the neural mechanisms that support this bias in spatial orienting are unknown. In the present study, participants learned to orient to a particular quadrant of a scene (high-value quadrant) to maximize monetary gains. This learning was scene-specific, with the high-value quadrant varying across different scenes. During a subsequent test phase, participants were faster at identifying a target if it appeared in the high-value quadrant (valid), and initial saccades were more likely to be made to the high-value quadrant. fMRI analyses during the test phase revealed learning-dependent priority signals in the bilateral caudate tail and superior colliculus, frontal eye field, substantia nigra, and insula, paralleling findings concerning feature-based value-driven attention. In addition, ventral regions typically associated with scene selective and spatial information processing, including the hippocampus, parahippocampal gyrus, and temporo-occipital cortex, were also implicated. Taken together, our findings offer new insights into the neural architecture subserving value-driven attention, both extending our understanding of nodes in the attention network previously implicated in feature-based value-driven attention and identifying a ventral network of brain regions implicated in rewards influence on scene-dependent spatial orienting.

neuroscience↗

Visual stimulation induces distinct forms of sensitization of On-Off direction-selective ganglion cell responses in the dorsal and ventral retina

Experience-dependent modulation of neuronal responses is a key attribute in sensory processing. In the mammalian retina, the On-Off direction-selective ganglion cell (On-Off DSGC) is well known for its robust direction selectivity. However, how the On-Off DSGC light responsiveness dynamically adjusts to the changing visual environment is underexplored. Here, we report that the On-Off DSGC can be transiently sensitized by prior stimuli. Notably, distinct sensitization patterns are found in dorsal and ventral DSGCs that receive visual inputs from lower and upper visual fields respectively. Although responses of both dorsal and ventral DSGCs to dark stimuli (Off responses) are sensitized, only dorsal cells show sensitization of responses to bright stimuli (On responses). Visual stimulation to the dorsal retina potentiates a sustained excitatory input from Off bipolar cells, leading to tonic depolarization of dorsal DSGCs. Such tonic depolarization propagates from the Off to the On dendritic arbor of the DSGC to sensitize its On response. We also identified a previously overlooked feature of DSGC dendritic architecture that can support direct electrotonic propagation between On and Off dendritic layers. By contrast, ventral DSGCs lack a sensitized tonic depolarization and thus do not exhibit sensitization of their On responses. Our results highlight a topographic difference in Off bipolar cell inputs underlying divergent sensitization patterns of dorsal and ventral On-Off DSGCs. Moreover, substantial crossovers between dendritic layers of On-Off DSGCs suggest an interactive dendritic algorithm for processing On and Off signals before they reach the soma.

neuroscience↗

Designed Nanoparticles Elicit Cross-Reactive Antibody Responses To Conserved Influenza Virus Hemagglutinin Stem Epitopes

Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that an alpha-helical fragment (helix-A) from the conserved stem region can be displayed on nanoparticles. The stem region of HA on these nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, H1-nanoparticles protected mice from lethal challenge with H1N1 influenza virus. Importantly, antibodies elicited by these nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity. The helix-A stem nanoparticle design represents a novel approach to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens up opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes.\n\nSignificanceInfluenza virus is a public health issue that affects millions of people globally each year. Commercial influenza vaccines are based on the hemagglutinin (HA) surface glycoprotein, which can change antigenically every year, demanding the manufacture of newly matched vaccines annually. HA stem epitopes have a higher degree of conservation than HA molecules contained in conventional vaccine formulations and we demonstrate that we are able to design nanoparticles that display hundreds of HA stem fragments on nanoparticles. These designed nanoparticles are heat-stable, elicit antibodies to the HA stem, confer protection in mouse challenge models, and show cross-reactivity between HA subtypes. This technology provides promising opportunities to improve seasonal vaccines, develop pandemic preparedness vaccines, and facilitate the development of a universal influenza vaccine.

microbiology↗