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An acute role for PirB in regulating cortical plasticity [electronic resource]
Bochner, David2013.Neural plasticity is high during developmental critical periods, then declines by adulthood. Here by acutely disrupting PirB function at different ages, we show that Paired immunoglobulin like receptor B (PirB) actively restricts plasticity both during and after the critical periopd. Chapter 1 introduces ocular dominance (OD) plasticity as a model of circuit and synaptic change, and presents a review of the literature on the study of mechanisms of OD plasticity, critical period timing, and manipulations that can alter plasticity later in life. Chapter 2 presents an overview of the methodological approaches used. PirB function was disrupted with temporal precision via either a conditional PirB allele or by minipump infusion of a soluble PirB ectodomain into mouse visual cortex. Chapter 3 details the effects of disrupting PirB function on plasticity in healthy animals. OD plasticity is enhanced not only during the critical period, but also when PirB function is disrupted in adulthood. The effects of adult deletion can occur even when PirB is only lost in excitatory neurons of the forebrain. Acute blockade of PirB for 10 days after the close of the critical period increases spine density on apical and basolateral dendrites of Layer 5 pyramidal neurons. Chapter 4 presents a proof of concept for therapeutic disruption of PirB function in cases of neurological dysfunction and disease. Long term monocular deprivation (LTMD) during the critical period leads to a lasting loss of vision in the deprived eye and to a decrease in dendritic spine density that does not recover even with subsequent binocular vision. However, acute blockade of PirB following LTMD allows for full recovery of spine density. MeCP2308/y mice, a mouse model of Rett Syndrome (a syndromic autism), were found to have increased MHC Class I expression and a concurrent loss of OD plasticity during the critical period, which can be rescued by acute blockade of PirB. Taken together, these results imply that mechanisms for enhanced structural and functional plasticity are present in adult visual cortex but are actively repressed by PirB. By removing negative regulators such as PirB, we show that it is possible to engage these endogenous mechanisms to facilitate recovery from otherwise irreversible effects of dysfunctional development. Our observations suggest that similar manipulations may be useful in other situations where restoring synaptic plasticity and increasing spine density have therapeutic value.
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With everything we've got : a personal anthology of Yiddish poetry
1st ed. - Austin, TX : Host Publications, c2009."A bilingual English/Yiddish poetry anthology"--Provided by publisher.
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Terror train [videorecording]
Beverly Hills, Calif. : Twentieth Century Fox Home Entertainment, c2004.A knife-wielding psycho crashes a New Year's Eve party held aboard a chartered train and begins slaughtering the guests one by one.
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