Biomedical subjects

Yuichi Sakumura

Publications and source records attributed to Yuichi Sakumura.

5 recordsLinked to original sources

PubMed2006

Shootin1: A protein involved in the organization of an asymmetric signal for neuronal polarization.

Neurons have the remarkable ability to polarize even in symmetrical in vitro environments. Although recent studies have shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized signals are organized without asymmetric cues. We describe a novel protein, named shootin1, that became up-regulated during polarization of hippocampal neurons and began fluctuating accumulation among multiple neurites. Eventually, shootin1 accumulated asymmetrically in a single neurite, which led to axon induction for polarization. Disturbing the asymmetric organization of shootin1 by excess shootin1 disrupted polarization, whereas repressing shootin1 expression inhibited polarization. Overexpression and RNA interference data suggest that shootin1 is required for spatially localized phosphoinositide-3-kinase activity. Shootin1 was transported anterogradely to the growth cones and diffused back to the soma; inhibiting this transport prevented its asymmetric accumulation in neurons. We propose that shootin1 is involved in the generation of internal asymmetric signals required for neuronal polarization.

Amino Acid Sequence↗

PubMed2006

The role of short-term depression in sustained neural activity in the prefrontal cortex: a simulation study.

Recent experimental researches have suggested that sustained neural activity in the prefrontal cortex is a process of memory retention in decision making. Previous theoretical studies indicate that a balance between recurrent excitation and feedback inhibition is important for sustaining the activity. To investigate a plausible balancing mechanism, we simulated a biophysically realistic network model. Our model shows that short-term depression (STD) enables the network to sustain its activity despite the presence of long-term inhibition by GABA(B) receptors and that the sustained firing rates have a bell-shaped dependence on the degree of STD. By analyzing the neural network dynamics, we show that the bell-shaped dependence on STD is formed by destabilizing the balance with either excessive or insufficient STD. We also show that the optimal degree of STD has a linear relationship with the neural network size. These results suggest that STD provides a balancing mechanism and controls levels of sustained activities of various size networks.

Action Potentials↗

PubMed2005

Local signaling with molecular diffusion as a decoder of Ca2+ signals in synaptic plasticity.

Synaptic plasticity is induced by the influx of calcium ions (Ca2+) through N-methyl-D-aspartate receptors (NMDARs), and the direction and strength of the response depend on the frequency of the synaptic inputs. Recent studies have shown that the direction of synaptic plasticity is also governed by two distinct NMDAR subtypes (NR1/NR2A, NR1/NR2B). How are the different types of regulation (frequency-dependent and receptor-specific) processed simultaneously? To clarify the molecular basis of this dual dependence of synaptic plasticity, we have developed a mathematical model of spatial Ca2+ signaling in a dendritic spine. Our simulations revealed that calmodulin (CaM) activation in the vicinity of NMDARs is strongly affected by the diffusion coefficient of CaM itself, and that this 'local CaM diffusion system' works as a dual decoder of both the frequency of Ca2+ influxes and their postsynaptic current shapes, generated by two NMDAR subtypes, implying that spatial factors may underlie the complicated regulation scheme of synaptic plasticity.

Animals↗

PubMed2005

Stochastic resonance with differential code in feedforward network with intra-layer random connections.

We examined stochastic resonance with a differential coding scheme using a multilayer feedforward neural network which is composed of intra-layer connections. We show that the network, with random synaptic connections in each layer, encodes an input signal into a spike coherence that represents temporal differences among the inputs. We also demonstrate that both internal and external noise enhance the detection of weak signals. Finally, we discuss how the feedforward network with intra-layer random connections is similar to a membrane in its sensitivity to and amplification of a change in stimulus and suggest that the intensity of internal noise may be tuned in a real brain.

Computer Simulation↗

PubMed2005

A molecular model for axon guidance based on cross talk between rho GTPases.

To systematically understand the molecular events that underlie biological phenomena, we must develop methods to integrate an enormous amount of genomic and proteomic data. The integration of molecular data should go beyond the construction of biochemical cascades among molecules to include tying the biochemical phenomena to physical events. For the behavior and guidance of growth cones, it remains largely unclear how biochemical events in the cytoplasm are linked to the morphological changes of the growth cone. We take a computational approach to simulate the biochemical signaling cascade involving members of the Rho family of GTPases and examine their potential roles in growth-cone motility and axon guidance. Based on the interactions between Cdc42, Rac, and RhoA, we show that the activation of a Cdc42-specific GEF resulted in switching responses between oscillatory and convergent activities for all three GTPases. We propose that the switching responses of these GTPases are the molecular basis for the decision mechanism that determines the direction of the growth-cone expansion, providing a spatiotemporal integration mechanism that allows the growth cone to detect small gradients of external guidance cues. These results suggest a potential role for the cross talk between Rho GTPases in governing growth-cone movement and axon guidance and underscore the link between chemodynamic reactions and cellular behaviors.

Animals↗