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Browsing by Subject "Dendritic spines"

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    ARP2/3 complex has a neuroprotective role and is required for mature dendritic spine head morphology
    (2010-08) Maldonado, Marcela
    Several lines of evidence suggest that Arp2/3 may play a role in regulating dendritic spine morphology. First, inhibition of the Arp2/3 activators N-WASP, Cortactin, and Wave alters spine morphology and density (Racz and Weinberg 2004, Pipel and Segal 2005, Soderling et al. 2007b, Wegner et al. 2008). Second, electron microscopy of dendritic spines revealed that the actin filaments within the spine head appear to be organized in "Y" shaped branches (Fifkova and Delay 1982). Since, Arp2/3 is the only complex known to make "Y" branched actin filaments, the presence of such branches in spine heads strongly suggests that Arp2/3 is involved in actin polymerization in spines. Consequently, the general hypothesis for my doctoral work is that if Arp2/3 is a major regulator of dendritic spine morphology, then Arp2/3 will be enriched in dendritic spines heads and inhibition of Arp2/3 activity will alter the number and/or morphology of dendritic spines. Our results show Arp2/3 localization within the dendritic spine heads of cultured hippocampal neurons. However, we observed Arp2/3 redistribution within dendritic shafts in response to induced synaptic activity. Temporal inhibition of Arp2/3 function during dendritic spine development showed severe morphological consequence in mature cultures. Finally, in collaboration with Dr. Robert Meller of Dow Neurobiology Laboratory at Legacy Research, Legacy Health in Portland Oregon, we show that Arp2/3 has a neuroprotective role of in ischemia tolerance.
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    mGluR5 Structural Plasticity in the Nucleus Accumbens: Characterization, Mechanism, and Sex Differences
    (2017-10) Gross, Kellie S
    The group I metabotropic glutamate receptors, mGluR1 and mGluR5, are important modulators of neuronal signaling and plasticity. One specific way that group I mGluRs appear to influence excitatory neurotransmission is through the remodeling of neuronal structure by inducing changes to dendritic spines. However, group I mGluR spine remodeling has only been studied in an extremely limited number of regions and cell types, leaving the contribution of this mechanism to plasticity in many systems unknown. Group I mGluRs, especially mGluR5, have been associated with the synaptic plasticity in the reward circuitry of the brain that is believed to underlie addiction. Structural changes in this circuitry, particularly in the nucleus accumbens (NAc) are strongly correlated with the development and maintenance of addiction. Yet a potential relationship between mGluR5 signaling and spine plasticity in the NAc has not been directly studied. Here, the effects of mGluR5 signaling on spine plasticity in medium spiny neurons of the NAc are characterized, with particular attention on the sex differences and hormonal regulation of these effects. Activation of mGluR5 signaling is found to decrease spine density in the NAc with sex differences in subregion specificity. Additionally, primary gonadal hormones are found to trigger mGluR5 signaling to produce structural modulation in the NAc, with previous evidence implicating mGluR5 in estradiol-induced spine changes in this region in females, and research here finding a similar, novel role for androgen signaling in males. The mechanisms of mGluR5-mediated spine plasticity are also explored. Endocannabinoid signaling was found to be required for mGluR5-induced spine decreases in the male NAc, and spine changes were found to be correlated with a change in NAc F-actin content. Collectively, these results indicate that mGluR5 signaling results in structural plasticity in a region that is critical to reward in a sex-dependent manner, suggesting that the activity of this receptor might contribute differently to both natural and pathological motivated behavior in males and females.