Biology subjects

Honore, C.

Publications and source records attributed to Honore, C..

3 recordsLinked to original sources

bioRxiv2022

Visual Perception of 3D Space and Shape in Time - Part I: 2D Space Perception by 2D Linear Translation

Visual perception plays a critical role in navigating space and extracting useful semantic information crucial to survival. To identify distant landmarks, we constantly shift gaze vectors through saccades, while still maintaining the visual perception of stable allocentric space. How can we sustain stable allocentric space so effortlessly? To solve this question, we have developed a new concept of NHT (Neural Holography Tomography). This model states that retinotopy is invisible (not available to consciousness) and must be converted to a time code by traveling alpha brainwaves to perceive objects consciously. According to this framework, if identical alpha phases are continually assigned to a landmark, we perceive its exact and consistent allocentric location. To test this hypothesis, we designed reaction time (RT) experiments to observe evidence of the predicted space-to-time conversion. Various visual stimuli were generated at a wide range of eccentricities either on a large TV (up to 40{degrees}) or by LED strips on a hemispherical dome (up to 60{degrees}). Participants were instructed to report the observed patterns promptly under either covert (no eye movement) or overt (with eye movement) conditions. As predicted, stimuli presented at the center of fixation always produced the fastest RTs. The additional RT delay was precisely proportional to the eccentricity of the peripheral stimulus presentation. Furthermore, both covert and overt attention protocols created the same RT delays, and trajectories of saccadic eye motions were in parallel to the overt RT vs. eccentricity. These findings strongly support our NHT model, in which the observed RT-eccentricity dependence is indicative of the spatiotemporal conversion required for maintaining a stable allocentric frame of reference. That is, we perceive space by time.

neuroscience↗

bioRxiv2022

Visual Perception of 3D Space and Shape in Time - Part III: 2D Shape Recognition by Log-Scaling

Human vision has a remarkable ability to recognize complex 3D objects such as faces that appear with any size and 3D orientations at any 3D location. If we initially memorize a face only with a normalized size and viewed from directly head on, the direct comparison between the one-sized memory and a new incoming image would demand tremendous mental frame translations in 7D. How can we perform such a demanding task so promptly and reliably as we experience the objects in the world around us? Intriguingly, our primary visual cortex exhibits a 2D retinotopy with a log-polar coordinate system, where scaling up/down of shape is converted to linear frame translation. As a result, mental scaling can be performed by linearly translating the memory or the perceptual image until they overlap with each other. According to our new model of NHT (Neural Holography Tomography), alpha brainwaves traveling at a constant speed can conduct this linear translation. With this scheme, every scaling up/down by a factor of two should take the same amount of extra mental time to recognize a smaller/larger face. To test this hypothesis, we designed a reaction time (RT) experiment, where participants were first asked to memorize sets of unfamiliar faces with a given specific size (4{degrees} or 8{degrees}). Following the memorization phase, similar stimuli with a wide range of sizes (from 1{degrees} to 32{degrees}) were presented, and RTs were recorded. As predicted, the increase in RT was proportional to the scaling factor in the log scale. Furthermore, we observed that RTs were fastest for 8{degrees} faces even if the memorized face was 4{degrees}. This supports our hypothesis that we always memorize faces at the exact size of ~8 {degrees}. To our surprise, the increases in RT were also consistent with the mentally-estimated depth sensation, which indicates that the apparent size of the recognized face can create a proper depth sensation.

neuroscience↗

bioRxiv2021

Extensive NEUROG3 occupancy in the human pancreatic endocrine gene regulatory network

ObjectiveMice lacking the bHLH transcription factor (TF) Neurog3 do not form pancreatic islet cells, including insulin secreting beta cells, causing diabetes. In human, homozygous mutations of NEUROG3 manifest with neonatal or childhood diabetes. Despite this critical role in islet cell development, the precise function and downstream genetic programs regulated directly by NEUROG3 remain elusive. We therefore mapped genome-wide NEUROG3 occupancy in human induced pluripotent stem cell (iPSC)-derived endocrine progenitors and determined NEUROG3 dependency of associated genes to uncover direct targets. MethodsWe generated a novel hiPSC line (NEUROG3-HA-P2A-Venus), where NEUROG3 is HA-tagged and fused to a self-cleaving fluorescent VENUS reporter. We used the CUT&RUN technique to map NEUROG3 occupancy and epigenetic marks in pancreatic endocrine progenitors (PEP) differentiated from this hiPSC line. We integrated NEUROG3 occupancy data with chromatin status and gene expression in PEPs and their NEUROG3-dependence. In addition, we searched whether NEUROG3 binds type 2 diabetes mellitus (T2DM)-associated variants at the PEP stage. ResultsCUT&RUN revealed a total of 863 NEUROG3 binding sites assigned to 1268 unique genes. NEUROG3 occupancy was found at promoters as well as at distant cis-regulatory elements frequently overlapping within PEP active enhancers. De novo motif analyses defined a NEUROG3 consensus binding motif and suggested potential co-regulation of NEUROG3 target genes by FOXA, RFX or PBX transcription factors. Moreover, we found that 22% of the genes downregulated in NEUROG3-/- hESC-derived PEPs are bound by NEUROG3 and thus likely to be directly regulated. NEUROG3 targets include transcription factors known to have important roles in islet cell development or function, such as NEUROD1, PAX4, NKX2-2, SOX4, MLXIPL, LMX1B, RFX3, and NEUROG3 itself. Remarkably, we uncovered that NEUROG3 binds transcriptional regulator genes with enriched expression in human fetal pancreatic alpha (e.g., IRX1, IRX2), beta (e.g., NKX6-1, SMAD9, ISX, TFCP2L1) and delta cells (ERBB4) suggesting that NEUROG3 could control islets subtype programs. Moreover, NEUROG3 targets genes critical for insulin secretion in beta cells (e.g., GCK, ABCC8/KCNJ11, CACNA1A, CHGA, SCG2, SLC30A8 and PCSK1). In addition, we unveiled a panel of ncRNA potentially regulated by NEUROG3. Lastly, we identified several T2DM risk SNPs within NEUROG3 peaks suggesting a possible developmental role of NEUROG3 in T2DM susceptibility. ConclusionMapping of NEUROG3 genome occupancy in PEPs uncovers an unexpectedly broad, direct control of the endocrine gene regulatory network (GRN) and raises novel hypotheses on how this master regulator controls islet and beta cell differentiation. HighlightsO_LINEUROG3 CUT&RUN analysis revealed 1268 target genes in human pancreatic endocrine progenitors (PEPs) C_LIO_LINEUROG3 binding sites overlap with active chromatin regions in PEPs. C_LIO_LI1/5 of the genes downregulated in NEUROG3-/- hESC-derived PEPs are bound by NEUROG3. C_LIO_LINEUROG3 targets islet specific TFs and regulators of insulin secretion. C_LIO_LISeveral T2DM risk allelles lie within NEUROG3 bound regions. C_LI

genomics↗