Doctoral Dissertations
Date of Award
12-2021
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Major
Biochemistry and Cellular and Molecular Biology
Major Professor
Keerthi Krishnan
Committee Members
Brad Binder, Rebecca Prosser, Rachel Patton McCord, Matthew Cooper
Abstract
Rett Syndrome (RTT) is a neurological disorder caused by mutations in MECP2, a gene expression regulator. The emerging hypothesis of RTT pathogenesis is that RTT is a sensory processing disorder which causes the onset of higher-order cognitive and social communication deficits seen in syndromic patients. Using a female Mecp2-heterozygous (Het) mouse model of RTT, our lab showed MECP2 is essential for regulating experience-dependent plasticity, measured by perineuronal net (PNN) expression in the adult auditory cortex during the pup gathering paradigm. PNNs are extracellular matrix structures that form around cortical inhibitory interneurons solidifying synaptic connections made after new experiences. As the pup gathering paradigm is multisensory, we chose to investigate how MECP2 regulates the timing of experience-dependent plasticity within another sensory modality important to the behavior: somatosensation. Through whole brain manual quantification of PNN expression within the primary somatosensory cortex (SS1) in the adult Het brains before (Naïve) and after (Sur) pup gathering behavior, we found an increase in PNN density in the Naïve and SurHet SS1. Atypical increase of PNN density within the NaïveHet SS1 suggested adult Hets are unable to process tactile information causing inefficient pup retrieval. We confirmed that adult Hets have deficits in tactile perception through simple whisker-based tactile tasks (Tac). The adult atypical NaïveHet PNN expression in SS1 is not present between 6-week-old (WO) NaïveHet and WT females, suggesting these animals would not present with the same tactile phenotypes as the adults. 6 WO Hets do not present with tactile perception deficits but are inefficient at the pup gathering behavior. Whole brain quantification of PNN density in the 6 WO Tac brains showed little significant alterations in PNN density between the TacHet and TacWT SS1. Comparatively, we found a significant increase in SurHet SS1 PNN density compared to SurWT and NaïveHet, which was present in all subregions. Together, these data suggest that MECP2 deficiency affects experience-dependent plasticity, as measured by PNN expression, during complex multisensory but not simple tactile behaviors within the SS1, in an age-dependent manner.
Recommended Citation
Layo-Carris, Dana E., "Identification of extracellular matrix plasticity during tactile sensation in a female mouse model of Rett Syndrome. " PhD diss., University of Tennessee, 2021.
https://trace.tennessee.edu/utk_graddiss/7047
Included in
Behavioral Neurobiology Commons, Cell Biology Commons, Molecular and Cellular Neuroscience Commons