Biology subjects

Sugihara, I.

Publications and source records attributed to Sugihara, I..

5 recordsLinked to original sources

bioRxiv2024

Developmental transformations of Purkinje cells tracked by DNA electrokinetic mobility

Brain development relies on orchestrated placement and timing of neurogenesis in progenitor zones to produce the expansive cellular diversity of the brain. We took advantage of bioelectric interactions between DNA and embryonic tissue to perform "stereo-tracking", a developmental targeting strategy that differentially labels cells positioned at different depths within intact progenitor zones. This three-dimensional labeling was achieved by delivery of plasmids with distinct electrokinetic mobilities into neural progenitor zones in utero. We applied stereo-tracking with light sheet imaging in the cerebellum and identified that Purkinje cells follow embryonically committed developmental trajectories linking distinct progenitor zone fields to the topography of the mature cerebellar cortex. In the process of stereo-tracking, we identified a previously unreported subcellular structure on the axon initial segment of Purkinje cells. These structures, we termed "axon bubbles", are developmentally timed and differentially labeled by lipid-modified proteins. Our findings demonstrate key rules that orchestrate the stereotyped transformations from fetal progenitors into mature networks of neuronal circuits, and demonstrate the potential of progenitor zone stereo-tracking to reveal new biology within intact developing systems.

neuroscience↗

bioRxiv2021

Cerebellar connectivity maps embody individual adaptive behavior

From planification to execution, cerebellar microcircuits encode different features of skilled movements. However, it is unknown whether cerebellar synaptic connectivity maps encode movement features in a motor context specific manner. Here we investigated the spatial organization of excitatory synaptic connectivity in mice cerebellar cortex in different locomotor contexts: during development and in normal, trained or altered locomotor conditions. We combined optical, electrophysiological and graph modelling approaches to describe synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs). Synaptic map maturation during development revealed a critical period in juvenile animals before the establishment of a stereotyped functional organization in adults. However, different locomotor conditions lead to specific GC-PC connectivity maps in PCs. Ultimately, we demonstrated that the variability in connectivity maps directly accounts for individual specific behavioral features of mice locomotion, suggesting that GC-PC networks encode a general motor context as well as individual specific internal models underlying motor adaptation.

neuroscience↗

bioRxiv2020

Heterogeneity of intrinsic excitability in Purkinje cells linked with longitudinal zebrin zones in the mouse cerebellum

Heterogeneous populations of Purkinje cells (PCs), classified into zebrin-positive (Z+) and - negative (Z-) types, are arranged into separate longitudinal zones and are involved in different types of cerebellar learning. However, the electrophysiological phenotype that is brought about by the zebrin expression has not been much clarified in PCs. We compared electrophysiological characteristics in the soma and parallel fiber (PF)-PC synapse in Z+ and Z- PCs located in identified vermal and hemispheric zones in cerebellar slices in zebrin-reporter mice. Intrinsic excitability, intrinsic plasticity and PF-PC synaptic long term potentiation (LTP) occurred more strongly in Z- Purkinje cells than in Z+ PCs. The enhanced intrinsic plasticity was correlated with the reduction of medium-time-course after-hyperpolarization (mAHP) only in Z- PCs. These differences, which seem to be produced by the zebrin-linked expression of other functional molecules, may tune Z+ and Z- PCs to zone-specific cerebellar functions.

neuroscience↗

bioRxiv2020

Striped distribution pattern of Purkinje cells of different birthdates in the mouse cerebellar cortex studied with the Neurog2-CreER transgenic line

Heterogeneity of Purkinje cells (PCs) that are arranged into discrete longitudinal stripes in the cerebellar cortex is related to the timing of PC generation. To understand the cerebellar compartmental organization, we mapped the PC birthdate (or differentiation timing) in the entire cerebellar cortex. We used the birthdate-tagging system of neurog2-CreER (G2A) mice hybridized with the AldocV strain which clarifies the zebrin (aldolase C) longitudinal striped pattern. The pattern of the birthdate-dependent PC distribution was arranged consistently into longitudinally-oriented stripes throughout almost all lobules except for the nodulus, paraflocculus and flocculus, in which distinct stripes were observed.Boundaries of the PC birthdate stripes were found either in the middle or coincided with that of the zebrin stripes. PCs in each birthdate stripe were born in various periods between embryonic day (E) 10.0 and E 13.5. In the vermis, PCs were chronologically distributed from lateral to medial stripes. In the paravermis, PCs of early birthdates were distributed in the long lateral zebrin-positive stripe (stripe 4+//5+) and the medially neighboring narrow zebrin-negative substripe (3d-//e2-), while PCs of late birthdates were distributed in the rest of all paravermal areas. In the hemisphere, PCs of early and late birthdates were intermingled in the majority of areas. The results indicate that the birthdate of a PC is a partial determinant for the zebrin compartment in which it is located. However, the correlation between the PC birthdate and the zebrin compartmentalization is not simple, and distinct among the vermis, paravermis, hemisphere, nodulus, and flocculus. HighlightsBirthdates of Purkinje cells (PCs) were mapped on the cerebellar zebrin striped pattern by using Neurog2-CreER (G2A) mice. The vermis, paravermis, hemisphere, nodulus, and flocculus had distinct longitudinally-striped patterns of PC birthdate distribution. PCs in each birthdate stripe were born in various periods between embryonic day (E) 10.0 and E 13.5. Boundaries of PC birthdate distributions were located at the boundaries of zebrin stripes or in the middle of a zebrin stripe. The results indicate that the PC birthdate is a partial determinant for the zebrin compartment in which a PC is located.

neuroscience↗

bioRxiv2019

Convergence of unisensory-evoked signals via multiple pathways to the cerebellum

The cerebellum receives signals directly from peripheral sensory systems and indirectly from the neocortex. To reveal how these different types of signals are processed in the cerebellar cortex, in vivo whole-cell recordings from granule cells and unit recordings from Purkinje cells were performed in mice in which primary somatosensory cortex (S1) could be optogenetically inhibited. Tactile stimulation of the upper lip produced two-phase granule cell responses (with latencies of [~] 8 ms and 28 ms), for which only the late phase was S1 dependent. Complex spikes and the late phase of simple spikes in Purkinje cells were also S1 dependent. These results indicate that individual granule cells integrate convergent inputs from the periphery and neocortex, and send their outputs to Purkinje cells, which then combine those signals with climbing fiber signals from the neocortex.

neuroscience↗