Biology subjects

Yu, H.-H.

Publications and source records attributed to Yu, H.-H..

6 recordsLinked to original sources

bioRxiv2025

Genetic Network Shaping Kenyon Cell Identity and Function in Drosophila Mushroom Bodies

Revealing the molecular mechanisms underlying neuronal specification and acquisition of specific functions is key to understanding how the nervous system is constructed. In the Drosophila brain, Kenyon cells (KCs) are sequentially generated to assemble the backbone of the mushroom body (MB). Broad-complex, tramtrack and bric-{square}-brac zinc finger transcription factors (BTBzf TFs) specify early-born KCs, whereas the essential TFs for specifying late-born KCs remain unidentified. Here, we report that Pipsqueak domain-containing TF Eip93F promotes the identity of late-born KCs by reciprocally regulating gene expression in main KC types. Moreover, Eip93F not only regulates the expression of calcium channel Ca-1T in late-born KCs to functionally control animal behavior, but it also forms a genetic network with BTBzf TFs to specify the identities of main KC types. Our study provides crucial information linking KC-type diversification to unique function acquisition in the adult MB.

developmental biology↗

bioRxiv2021

VISUAL CORTICAL AREA MT IS REQUIRED FOR DEVELOPMENT OF THE DORSAL STREAM AND ASSOCIATED VISUOMOTOR BEHAVIOURS

The middle temporal (MT) area of the extrastriate visual cortex has long been studied in adulthood for its distinctive physiological properties and function as a part of the dorsal stream, yet interestingly possesses a similar maturation profile as the primary visual cortex (V1). Here we examined whether an early-life lesion of MT altered the dorsal stream development and the behavioural precision of reaching to grasp sequences. We observed permanent changes in the anatomy of cortices associated with both reaching (PE and MIP) and grasping (AIP), as well as in reaching and grasping behaviours. In addition, we observed a significant impact on the anatomy of V1 and the direction sensitivity of V1 neurons in the lesion projection zone. These findings indicate that area MT is a crucial node for the development of the primate vision, impacting both V1 and areas in the dorsal visual pathway known to mediate visually guided manual behaviours. TeaserThe early life loss of visual area MT leads to significant anatomical, physiological and behavioural changes.

neuroscience↗

bioRxiv2019

A \"twisted\" visual field map in the primate cortex predicted by topographic continuity

Adjacent neurons in visual cortex have overlapping receptive fields within and across area boundaries, an arrangement which is theorized to minimize wiring cost. This constraint is thought to create retinotopic maps of opposing field sign (mirror and non-mirror representations of the visual field) in adjacent visual areas, a concept which has become central in current attempts to subdivide the cortex. We modelled a realistic developmental scenario in which adjacent areas do not mature simultaneously, but need to maintain topographic continuity across their borders. This showed that the same mechanism that is hypothesized to maintain topographic continuity within each area can lead to a more complex type of retinotopic map, consisting of sectors with opposing field sign within a same area. Using fully quantitative electrode array recordings, we then demonstrate that this type of map exists in the primate extrastriate cortex.

neuroscience↗

bioRxiv2019

Basis for discrimination by engineered CRISPR/Cas9 enzymes

CRISPR/Cas9 is a programmable genome editing tool that has been widely used for biological applications. While engineered Cas9s have been reported to increase discrimination against off-target cleavage compared with wild type Streptococcus pyogenes (SpCas9) in vivo, the mechanism for enhanced specificity has not been extensively characterized. To understand the basis for improved discrimination against off-target DNA containing important mismatches at the distal end of the guide RNA, we performed kinetic analyses on the high-fidelity (Cas9-HF1) and hyper-accurate (HypaCas9) engineered Cas9 variants. While DNA unwinding is the rate-limiting step for on-target cleavage by SpCas9, we show that chemistry is seriously impaired by more than 100-fold for the high-fidelity variants. The high-fidelity variants improve discrimination by slowing the rate of chemistry without increasing the rate of DNA rewinding--the kinetic partitioning favors release rather than cleavage of a bound off-target substrate because chemistry is slow. Further improvement in discrimination may require engineering increased rates of dissociation of off-target DNA.

biochemistry↗

bioRxiv2019

Topographic organization of the third tier dorsomedial visual cortex in the macaque

The boundaries of the visual areas located anterior to V2 in the dorsomedial region of the macaque cortex remain contentious. This region is usually conceptualized as including two functional subdivisions: the dorsal component of area V3 (V3d), laterally, and another area, named the parietooccipital area (PO) or V6, medially. However, the nature of the putative border between V3d and PO/V6 has remained undefined. We recorded the receptive fields of multiunit clusters in adult male macaques, and reconstructed the locations of recording sites using histological sections and \"unfolded\" cortical maps. Immediately adjacent to dorsomedial V2 we observed a representation of the lower contralateral quadrant, which represented the vertical meridian at its rostral border. This region, corresponding to V3d of previous studies, formed a simple eccentricity gradient, from approximately <5{degrees} in the annectant gyrus, to >60{degrees} in the parietooccipital sulcus. However, there was no topographic reversal where one would expect to find the border between V3d and PO/V6. Rather, near the midline, this lower quadrant map continued directly into a representation of the peripheral upper visual field, without an intervening lower quadrant representation that could be unambiguously assigned to PO/V6. Thus, V3d and PO/V6 form a continuous topographic map, which includes parts of both quadrants. Together with previous observations that V3d and PO/V6 are both densely myelinated relative to adjacent cortex, and share similar input from V1, these results suggest that they are parts of a single area, which is distinct from the one forming the ventral component of the third tier complex.\n\nSignificance statementThe primate visual cortex has a large number of areas. Knowing the extent of each visual area, and how they can be distinguished from each other, are essential for the interpretation of experiments aimed at understanding visual processing. Currently, there are conflicting models of the organization of the dorsomedial visual cortex rostral to area V2 (one of the earliest stages of cortical processing of vision). By conducting large-scale electrophysiological recordings, we found that what were originally thought to be distinct areas in this region (dorsal V3, and the parietooccipital area [PO/V6]), together form a single map the visual field. These results will help guide future functional studies, and the interpretation of the outcomes of lesions involving the dorsal visual cortex.

neuroscience↗

bioRxiv2017

The most informative neural code accounts for population heterogeneity

Perception is produced by reading out the representation of a sensory stimulus contained in the firing rates of a population of neurons. To examine experimentally how populations code information, a common approach is to decode a linearly-weighted sum of the neurons firing rates. This approach is popular because of its biological validity: weights in a computational decoder are analogous to synaptic strengths. For neurons recorded in vivo, weights are highly variable when derived through machine learning methods, but it is unclear what neuronal properties explain this variability, and how the variability affects decoding performance. To address this, we recorded from neurons in the middle temporal area (MT) of anesthetized marmosets (Callithrix jacchus) viewing stimuli comprising a sheet of dots that moved coherently in one of twelve different directions. We found that high gain and direction selectivity both predicted that a neuron would be weighted more highly in an optimised decoding model. Although learned weights differed markedly from weights chosen according to a priori rules based on a neurons tuning profile, decoding performance was only marginally better for the learned weights. In the models with a priori rules, selectivity is the best predictor of weighting, and defining weights according to a neurons preferred direction and selectivity improves decoding performance to very near the maximum level possible, as defined by the learned weights.\n\nNew & NoteworthyWe examined which aspects of a neurons tuning account for its contribution to sensory coding. Strongly direction-selective neurons were weighted most highly by machine learning algorithms trained to discriminate motion direction. Models with a priori defined decoding weights demonstrate that the learned weighting scheme causally improved direction representation by a neuronal population. Optimising decoders (using machine learning) lead to only marginally better performance than decoders based purely on a neurons preferred direction and selectivity.

neuroscience↗