Browsing by Subject "Dendritic Spines"

Now showing 1 - 4 of 4
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    Astrocytes refine cortical connectivity at dendritic spines.
    (Elife, 2014-12-17) Risher, WC; Patel, S; Kim, IH; Uezu, A; Bhagat, S; Wilton, DK; Pilaz, L; Singh Alvarado, J; Calhan, OY; Silver, DL; Stevens, B; Calakos, N; Soderling, SH; Eroglu, C
    During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.
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    Regulation of spine structural plasticity by Arc/Arg3.1.
    (Seminars in cell & developmental biology, 2018-05) Newpher, Thomas M; Harris, Scott; Pringle, Jasmine; Hamilton, Colleen; Soderling, Scott
    Dendritic spines are actin-rich, postsynaptic protrusions that contact presynaptic terminals to form excitatory chemical synapses. These synaptic contacts are widely believed to be the sites of memory formation and information storage, and changes in spine shape are thought to underlie several forms of learning-related plasticity. Both membrane trafficking pathways and the actin cytoskeleton drive activity-dependent structural and functional changes in dendritic spines. A key molecular player in regulating these processes is the activity-regulated cytoskeleton-associated protein (Arc), a protein that has diverse roles in expression of synaptic plasticity. In this review, we highlight important findings that have shaped our understanding of Arc's functions in structural and functional plasticity, as well as Arc's contributions to memory consolidation and disease.
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    Spine microdomains for postsynaptic signaling and plasticity.
    (Trends in cell biology, 2009-05) Newpher, Thomas M; Ehlers, Michael D
    Changes in the molecular composition and signaling properties of excitatory glutamatergic synapses onto dendritic spines mediate learning-related plasticity in the mammalian brain. This molecular adaptation serves as the most celebrated cell biological model for learning and memory. Within their micron-sized dimensions, dendritic spines restrict the diffusion of signaling molecules and spatially confine the activation of signal transduction pathways. Much of this local regulation occurs by spatial compartmentalization of glutamate receptors. Here, we review recently identified cell biological mechanisms regulating glutamate receptor mobility within individual dendritic spines. We discuss the emerging functions of glutamate receptors residing within sub-spine microdomains and propose a model for distinct signaling platforms with specialized functions in synaptic plasticity.
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    Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1.
    (The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015-09) Bukhari, Noreen; Burman, Poromendro N; Hussein, Ayan; Demars, Michael P; Sadahiro, Masato; Brady, Daniel M; Tsirka, Stella E; Russo, Scott J; Morishita, Hirofumi

    Unlabelled

    Experience-dependent cortical plasticity declines with age. At the molecular level, experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain if mice are raised in standard cages. Understanding the mechanism for the loss of permissive proteolytic activity is therefore a key link for improving function in adult brains. Using the mouse primary visual cortex (V1) as a model, we demonstrate that tPA activity in V1 can be unmasked following 4 d of monocular deprivation when the mice older than 2 months are raised in standard cages by the genetic removal of Lynx1, a negative regulator of adult plasticity. This was also associated with the reduction of stubby and thin spine density and enhancement of ocular dominance shift in adult V1 of Lynx1 knock-out (KO) mice. These structural and functional changes were tPA-dependent because genetic removal of tPA in Lynx1 KO mice can block the monocular deprivation-dependent reduction of dendritic spine density, whereas both genetic and adult specific inhibition of tPA activity can ablate the ocular dominance shift in Lynx1 KO mice. Our work demonstrates that the adult brain has an intrinsic potential for experience-dependent elevation of proteolytic activity to express juvenile-like structural and functional changes but is effectively limited by Lynx1 if mice are raised in standard cages. Insights into the Lynx1-tPA plasticity mechanism may provide novel therapeutic targets for adult brain disorders.

    Significance statement

    Experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain in correlation with the decline in cortical plasticity when mice are raised in standard cages. We demonstrated that removal of Lynx1, one of negative regulators of plasticity, unmasks experience-dependent tPA elevation in visual cortex of adult mice reared in standard cages. This proteolytic elevation facilitated dendritic spine reduction and ocular dominance plasticity in adult visual cortex. This is the first demonstration of adult brain to retain the intrinsic capacity to elevate tPA in an experience-dependent manner but is effectively limited by Lynx1. tPA-Lynx1 may potentially be a new candidate mechanism for interventions that were shown to activate plasticity in adult brain.