Using in vivo single neuron electrophysiology and population-mediated potentials in response to sound, Drs. Khaleel Razak, Devin Binder and Iryna Ethell of UC Riverside will determine the progression of auditory processing deficits over the course of development in Fmr1 KO mice, and will test hypothesized mechanisms of these deficits. In patients, sensory hypersensitivities often diminish with age; understanding the mechanisms of that effect is important in order to direct treatment development.
The study will evaluate the efficacy of novel candidate therapeutics for reducing functional and structural synaptic deficits in A1 in vivo across the age span. Notably, results with auditory event-related potentials (ERP) will be directly translatable to patients in Project 3. In vivo results are linked to cellular and local circuit mechanisms in Project 1 through common developmental, drug and gene-dependent regulation approaches.
- Sinclair D., Oranje B., Razak K. A., Siegel, S. J., Schmid S. Sensory processing in autism spectrum disorders and Fragile X syndrome-from the clinic to animal models. Neurosci Biobehav Rev. pii: S0149-7634(15)30318-3. doi: 10.1016/j.neubiorev.2016.05.029.
- Lovelace J. W., Wen T. H., Reinhard S., Hsu M. S., Sidhu H., Ethell I. M., Binder D. K., Razak K. A. Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome. Neurobiol Dis. 89, 126-35, (2016).
- Sidhu H., Dansie L. E., Hickmott P. W., Ethell D. W., Ethell I. M. Genetic removal of matrix metalloproteinase 9 rescues the symptoms of fragile X syndrome in a mouse model. J Neurosci. 34, 9867-79, (2014).
- Rotschafer S. E. and Razak K. A. Auditory processing in Fragile X Syndrome. Front Cell Neurosci. 8, 1-11, (2014).
- Carrasco M. M., Trujillo M. Razak K. Development of response selectivity in the mouse auditory cortex. Hear Res. 296, 107-20, (2013).
- Rotschafer S. and Razak K. Altered auditory processing in a mouse model of fragile X syndrome. Brain Res. 1506, 12-24, (2013).
- Dansie L. E., Phommahaxay K., Okusanya A. G., Uwadia J., Huang M., Rotschafer S. E., Razak K. A., Ethell D. W., Ethell I. M. Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice. 246, 186-98, (2013).