Biology subjects

Kawasaki, H.

Publications and source records attributed to Kawasaki, H..

4 recordsLinked to original sources

bioRxiv2018

YAP activity is necessary and sufficient for basal progenitor abundance and proliferation in the developing neocortex

The expansion of the neocortex during mammalian evolution has been linked to an enlargement of the subventricular zone during cortical development and an increase in the proliferation of the basal progenitors residing therein. Here, we explored a potential role of YAP, the major downstream effector of the Hippo signaling pathway, in proliferation of basal progenitors. We show that YAP expression and activity are high in ferret and human basal progenitors, which are known to exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. To induce YAP activity in mouse basal progenitors, we expressed a constitutively active YAP (CA-YAP). This resulted in an increase in proliferation of basal progenitor. In addition, CA-YAP expressing mouse basal progenitors promoted the production of upper-layer neurons. To investigate if YAP is required for the proliferation of basal progenitors, we pharmacologically interfered with the function of YAP in the developing ferret and human neocortex. This resulted in a decrease of cycling basal progenitors. In concert, genetical interference with the function of YAP in ferret developing neocortex resulted in decreased abundance of basal progenitors. Together, our data indicate that YAP promotes the proliferation of basal progenitors and suggest that changes in YAP activity levels contributed to the evolutionary expansion of the neocortex.

neuroscience↗

bioRxiv2018

Processing of Auditory Novelty Across the Cortical Hierarchy: An Intracranial Electrophysiology Study

Under the predictive coding hypothesis, specific spatiotemporal patterns of cortical activation are postulated to occur during sensory processing as expectations generate feedback predictions and prediction errors generate feedforward signals. Establishing experimental evidence for this information flow within cortical hierarchy has been difficult, especially in humans, due to spatial and temporal limitations of non-invasive measures of cortical activity. This study investigated cortical responses to auditory novelty using the local/global deviant paradigm, which engages the hierarchical network underlying auditory predictive coding over short ( local deviance; LD) and long ( global deviance; GD) time scales. Electrocorticographic responses to auditory stimuli were obtained in neurosurgical patients from regions of interest (ROIs) including auditory, auditory-related and prefrontal cortex. LD and GD effects were assayed in averaged evoked potential (AEP) and high gamma (70-150 Hz) signals, the former likely dominated by local synaptic currents and the latter largely reflecting local spiking activity. AEP LD effects were distributed across all ROIs, with greatest percentage of significant sites in core and non-core auditory cortex. High gamma LD effects were localized primarily to auditory cortex in the superior temporal plane and on the lateral surface of the superior temporal gyrus (STG). LD effects exhibited progressively longer latencies in core, non-core, auditory-related and prefrontal cortices, consistent with feedforward signaling. The spatial distribution of AEP GD effects overlapped that of LD effects, but high gamma GD effects were more restricted to non-core areas. High gamma GD effects had shortest latencies in STG and preceded AEP GD effects in most ROIs. This latency profile, along with the paucity of high gamma GD effects in the superior temporal plane, suggest that the STG plays a prominent role in initiating novelty detection signals over long time scales. Thus, the data demonstrate distinct patterns of information flow in human cortex associated with auditory novelty detection over multiple time scales.

neuroscience↗

bioRxiv2017

Correct laminar positioning in the neocortex influences proper dendritic and synaptic development

The neocortex is a six-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down Dcx, a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines and functional glutamatergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits.

neuroscience↗

bioRxiv2017

Surgically disconnected temporal pole exhibits resting functional connectivity with remote brain regions

Functional connectivity, as measured by resting-state fMRI, has proven a powerful method for studying brain systems in the context of behavior, development, and disease states. However, the relationship of functional connectivity to structural connectivity remains unclear. If functional connectivity relies on structural connectivity, then anatomical isolation of a brain region should eliminate functional connectivity with other brain regions. We tested this by measuring functional connectivity of the surgically disconnected temporal pole in resection patients (N=5; mean age 37; 2F, 3M). Functional connectivity was evaluated based on coactivation of whole-brain fMRI data with the average low-frequency BOLD signal from disconnected tissue in each patient. In sharp contrast to our prediction, we observed significant functional connectivity between the disconnected temporal pole and remote brain regions in each disconnection case. These findings raise important questions about the neural bases of functional connectivity measures derived from the fMRI BOLD signal.

neuroscience↗