235 research outputs found
Storage Capacity Diverges with Synaptic Efficiency in an Associative Memory Model with Synaptic Delay and Pruning
It is known that storage capacity per synapse increases by synaptic pruning
in the case of a correlation-type associative memory model. However, the
storage capacity of the entire network then decreases. To overcome this
difficulty, we propose decreasing the connecting rate while keeping the total
number of synapses constant by introducing delayed synapses. In this paper, a
discrete synchronous-type model with both delayed synapses and their prunings
is discussed as a concrete example of the proposal. First, we explain the
Yanai-Kim theory by employing the statistical neurodynamics. This theory
involves macrodynamical equations for the dynamics of a network with serial
delay elements. Next, considering the translational symmetry of the explained
equations, we re-derive macroscopic steady state equations of the model by
using the discrete Fourier transformation. The storage capacities are analyzed
quantitatively. Furthermore, two types of synaptic prunings are treated
analytically: random pruning and systematic pruning. As a result, it becomes
clear that in both prunings, the storage capacity increases as the length of
delay increases and the connecting rate of the synapses decreases when the
total number of synapses is constant. Moreover, an interesting fact becomes
clear: the storage capacity asymptotically approaches due to random
pruning. In contrast, the storage capacity diverges in proportion to the
logarithm of the length of delay by systematic pruning and the proportion
constant is . These results theoretically support the significance of
pruning following an overgrowth of synapses in the brain and strongly suggest
that the brain prefers to store dynamic attractors such as sequences and limit
cycles rather than equilibrium states.Comment: 27 pages, 14 figure
Factors That Influence Primary Cilium Length
Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells;this phenomenon is likely independent of glycogen synthase kinase-3β inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors
Neuroprotective Effects of Metallothionein Against Rotenone-Induced Myenteric Neurodegeneration in Parkinsonian Mice
Parkinson's disease (PD) is a neurodegenerative disease with motor symptoms as well as non-motor symptoms that precede the onset of motor symptoms. Mitochondrial complex I inhibitor, rotenone, has been widely used to reproduce PD pathology in the central nervous system (CNS) and enteric nervous system (ENS). We reported previously that metallothioneins (MTs) released from astrocytes can protect dopaminergic neurons against oxidative stress. The present study examined the changes in MT expression by chronic systemic rotenone administration in the striatum and colonic myenteric plexus of C57BL mice. In addition, we investigated the effects of MT depletion on rotenone-induced neurodegeneration in CNS and ENS using MT-1 and MT-2 knockout (MT KO) mice, or using primary cultured neurons from MT KO mice. In normal C57BL mice, subcutaneous administration of rotenone for 6 weeks caused neurodegeneration, increased MT expression with astrocytes activation in the striatum and myenteric plexus. MT KO mice showed more severe myenteric neuronal damage by rotenone administration after 4 weeks than wild-type mice, accompanied by reduced astroglial activation. In primary cultured mesencephalic neurons from MT KO mice, rotenone exposure induced neurotoxicity in dopaminergic neurons, which was complemented by addition of recombinant protein. The present results suggest that MT seems to provide protection against neurodegeneration in ENS of rotenone-induced PD model mice
Visualization of Astrocytic Primary Cilia in the Mouse Brain by Immunofluorescent Analysis Using the Cilia Marker Arl13b
In vertebrates, almost all somatic cells extend a single immotile cilium, referred to as a primary cilium. Increasing evidence suggests that primary cilia serve as cellular antennae in many types of tissues by sensing chemical or mechanical stimuli in the milieu surrounding the cells. In rodents an antibody to adenylyl cyclase 3 (AC3) has been widely used to label the primary cilia of neurons in vivo by immunostaining, whereas the lack of markers for the primary cilia of astrocytes has made it difficult to observe astrocytic primary cilia in vivo. Here, we obtained a visualization of astrocytic primary cilia in the mouse brain. In the somatosensory cortex, a large portion of neurons and astrocytes at postnatal day 10 (P10), and of neurons at P56 had AC3-positive primary cilia, whereas only approx. one-half of the astrocytes in the P56 mice carried primary cilia weakly positive for AC3. In contrast, the majority of astrocytes had ADP-ribosylation factor-like protein 13B (Arl13b)-positive primary cilia in the somatosensory cortex and other brain regions of P56 mice. The lengths of astrocytic primary cilia positive for Arl13b varied among the brain regions. Our data indicate that Arl13b is a noteworthy marker of astrocytic primary cilia in the brain
Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity
AbstractDopamine (DA) quinone as DA neuron-specific oxidative stress conjugates with cysteine residues in functional proteins to form quinoproteins. Here, we examined the effects of cysteine-rich metal-binding proteins, metallothionein (MT)-1 and -2, on DA quinone-induced neurotoxicity. MT quenched DA semiquinones in vitro. In dopaminergic cells, DA exposure increased quinoproteins and decreased cell viability; these were ameliorated by pretreatment with MT-inducer zinc. Repeated L-DOPA administration markedly elevated striatal quinoprotein levels and reduced the DA nerve terminals specifically on the lesioned side in MT-knockout parkinsonian mice, but not in wild-type mice. Our results suggested that intrinsic MT protects against L-DOPA-induced DA quinone neurotoxicity in parkinsonian mice by its quinone-quenching property
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