Undergraduate Honours Theses (Biology)
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Item Establishing a new protocol to investigate sensory adaptation in a mouse model of Rett Syndrome(2022) Kaban, TaylorThis project is a continuation of Farhoomand (2021). Dr. Farhoomand studied sensory adaptation in the hindlimb to primary somatosensory cortical pathway in a mouse model of Rett syndrome to better understand the loss of MeCP2 function in neuronal circuit and sensory processing. Cortical evoked responses (CERs) to vibratory tactile stimulation of the hind limb were assessed via intrinsic optical imaging (IOS) and intracortical local field potential recordings (LFPs) before, during, and after 1 hour of repetitive vibratory stimulation at 100hz. After 1 hour, the CER was reduced by approximately 40% in both Rett mice (RTT) and wild-type mice (WT). Reduced responses persisted for at least 60 minutes in wild-type mice but recovered to 90-100% of baseline within 15 – 30 minutes in Rett mice. Analysis of this phenomenon via LFP within the test train indicated that the reduced CER was due to an increase in short term adaptation during the 7-stimulus train that was retained in the WT mice but reversed rapidly in the RTT mice. We therefore propose that the persistent sensory adaptation differences between WT and RTT that are mediated by increased short-term adaptation may reflect enhanced feedback by inhibitory elements of circuits within the sensory pathway. The lack of the adaptation to persist after continuous stimulation in the RTT mice may therefore reflect a deficit in the capacity for activity dependent plasticity to consolidate. To determine if this is the case, this project sought to establish a new protocol to further probe this phenomenon of sensory adaptation with a larger cranial window that allows for the simultaneous recording of the CER from both hemispheres. We also seek to replace the piezo device with a new vibratory device that does not leave an artifact in the LFP data. To establish this new protocol this project sought to answer three main questions: (1) Can we reliably replace the piezo vibratory device with a motor device that is cheaper and doesn’t leave an artifact in the data. We found that while there was a significant difference in the timing of the CER after stimulus offset with the motor device, there was no significant difference in the variability of that timing, suggesting consistency with the motor device. We also found no significant difference in the sum of the peaks (mV) between the piezo device and one of the motor settings tested, and finally, we found no significant difference in the paired pulse ratio. In summary, the motor device can reliably replace the piezo device. (2) Do we see evidence for adaptation with the motor device? We found that there was evidence for adaptation, though there may be differences in the persistence of that adaptation. (3) Is there evidence for cross adaptation? We found that while there was a reduction in the CER after the adaptation phase, it wasn’t statistically significant (likely due to the small sample size of N=2). In summary, this project has established many successful aspects of a new protocol to further probe sensory adaptation. It has also paved a clear direction for the next steps in further progress towards our goal of providing a platform to understand some of the circuit level substrates of the sensory, learning, and cognitive deficits in RTT patients.