PERINEURONAL NETS IN HIPPOCAMPAL AREA CA2: REGULATION BY ACTIVITY AND DISEASE

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  • March 20, 2019
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  • CARSTENS, KELLY
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
Abstract
  • Perineuronal nets (PNNs) first appear in the brain during early postnatal development and increase until they are fully expressed in adulthood, often tracking the end of critical windows of synaptic plasticity1, 2. The experience-dependent development of PNNs in the brain is thought to function as a molecular brake on plasticity during the closure of these critical windows 3, 4. PNNs are typically associated with inhibitory neurons throughout the brain; however, I characterized a dense localization of PNNs surrounding a population of excitatory pyramidal neurons in hippocampal area CA2. I found that PNNs in CA2 function to restrict plasticity at CA2 synapses in mice 14-18 days old (P14-18). I also identified a novel window of plasticity in area CA2, P8-11, an age prior to the maturation of PNNs in CA2. PNNs are reportedly altered in several neurodevelopmental disorders such as temporal lobe epilepsy (TLE) and Rett syndrome. I found that PNNs are precociously increased and develop prematurely in a Rett mouse model. Moreover, PNNs appear to be at least one mechanism restricting plasticity prematurely in CA2 of the Rett model mouse. Finally, because PNNs are regulated by pathological activity, I characterize PNNs in a TLE mouse model. PNNs were attenuated in CA2 by age P45, but were unchanged at younger ages after the onset of seizures (P21). To further examine how activity regulates PNNs in CA2, we chemogenetically increased or decreased CA2 activity for five days and found that PNNs are inversely regulated by activity in CA2. Overall, these findings reveal a critical function for PNNs in restricting plasticity in CA2 and identify a novel, yet-to-be described, window of plasticity in the hippocampus.
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Advisor
  • Dudek, Serena
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2018
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