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Piber, M.

Publications and source records attributed to Piber, M..

2 recordsLinked to original sources
bioRxiv2023

ARID1B controls transcriptional programs of axon projection in the human corpus callosum

Mutations in ARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms in humans. The most common structural abnormality in the brain of ARID1B patients is agenesis of the corpus callosum (ACC). This condition is characterized by a partial or complete absence of the corpus callosum (CC), an interhemispheric white matter tract that connects distant cortical regions. Using human neural organoids, we identify a vulnerability of callosal projection neurons (CPNs) to ARID1B haploinsufficiency, resulting in abnormal maturation trajectories and dysregulation of transcriptional programs of CC development. Through a novel in vitro model of the CC tract, we demonstrate that ARID1B mutations reduce the proportion of CPNs capable of forming long-range projections, leading to structural underconnectivity phenotypes. Our study uncovers new functions of the mSWI/SNF during human corticogenesis, identifying cell-autonomous defects in axonogenesis as a cause of ACC in ARID1B patients. O_FIG O_LINKSMALLFIG WIDTH=193 HEIGHT=200 SRC="FIGDIR/small/539362v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@dd4e9aorg.highwire.dtl.DTLVardef@153a081org.highwire.dtl.DTLVardef@14e884corg.highwire.dtl.DTLVardef@d64081_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Human callosal projection neurons are vulnerable to ARID1B haploinsufficiency. (Top) During healthy development, callosal projection neurons (CPNs) project long interhemispheric axons, forming the corpus callosum (CC) tract, which can be modeled in vitro. (Bottom) In ARID1B patients, transcriptional dysregulation of genetic programs of CC development reduces the formation of long-range projections from CPNs, causing CC agenesis in vivo and underconnectivity phenotypes in vitro. C_FIG

neuroscience↗
bioRxiv2019

Brain-wide visual habituation networks in wild type and fmr1 zebrafish

Habituation is a form of learning during which animals stop responding to repetitive stimuli, and deficits in habituation are characteristics of several psychiatric disorders. Due to the technical challenges of measuring brain activity comprehensively and at cellular resolution, the brain-wide networks mediating habituation are poorly understood. Here we report brain-wide calcium imaging during visual learning in larval zebrafish as they habituate to repeated threatening loom stimuli. We show that different functional categories of loom-sensitive neurons are located in characteristic locations throughout the brain, and that both the functional properties of their networks and the resulting behavior can be modulated by stimulus saliency and timing. Using graph theory, we identify a principally visual circuit that habituates minimally, a moderately habituating midbrain population proposed to mediate the sensorimotor transformation, and downstream circuit elements responsible for higher order representations and the delivery of behavior. Zebrafish larvae carrying a mutation in the fmr1 gene have a systematic shift towards sustained premotor activity in this network, and show slower behavioral habituation. This represents the first description of a visual learning network across the brain at cellular resolution, and provides insights into the circuit-level changes that may occur in people with Fragile X syndrome and related psychiatric conditions.

neuroscience↗