Fragile X syndrome is the most common inherited cause of mental retardation. The disorder is caused by mutation in a gene, FMR1, that encodes the fragile X mental retardation protein (FMRP). How loss of FMRP produces mental retardation is not known. FMR1 knockout mice have been produced, providing a mouse model for fragile X syndrome. The experiments proposed in this application will use the mouse olfactory system to investigate the normal function of FMRP and the consequences of the protein's absence in knockout mice. FMRP is normally expressed in olfactory brain structures. The project has three specific aims. First, behavioral analyses will be conducted to determine how lack of FMRP results in impairment of memory formation for olfactory information. Second, electrophysiological methods will be used to determine how absence of FMRP alters synaptic function and synaptic plasticity in the primary olfactory cortex. Third, olfactory stimulation and learning paradigms will be used to determine how expression of FMRP is regulated by neuronal activity in the olfactory system. The results of these studies should provide new information regarding the function of FMRP in the normal brain and may identify behavioral or physiological functions that are reliably disrupted in mice lacking this important protein. Such new information would be vital for evaluating novel treatment strategies for a class of developmental disabilities. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC005793-05
Application #
7240562
Study Section
Special Emphasis Panel (ZRG1-BDCN-5 (01))
Program Officer
Davis, Barry
Project Start
2003-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
5
Fiscal Year
2007
Total Cost
$235,361
Indirect Cost
Name
University of Illinois at Chicago
Department
Psychiatry
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Larson, John; Munkácsy, Erin (2015) Theta-burst LTP. Brain Res 1621:38-50
Gocel, James; Larson, John (2012) Synaptic NMDA receptor-mediated currents in anterior piriform cortex are reduced in the adult fragile X mouse. Neuroscience 221:170-81
Smalheiser, Neil R; Lugli, Giovanni (2009) microRNA regulation of synaptic plasticity. Neuromolecular Med 11:133-40
Larson, John; Park, Thomas J (2009) Extreme hypoxia tolerance of naked mole-rat brain. Neuroreport 20:1634-7
Patel, Roseanne C; Larson, John (2009) Impaired olfactory discrimination learning and decreased olfactory sensitivity in aged C57Bl/6 mice. Neurobiol Aging 30:829-37
Larson, John; Kim, Daniel; Patel, Roseanne C et al. (2008) Olfactory discrimination learning in mice lacking the fragile X mental retardation protein. Neurobiol Learn Mem 90:90-102
Lugli, Giovanni; Torvik, Vetle I; Larson, John et al. (2008) Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain. J Neurochem 106:650-61
Larson, John; Jessen, Ruth E; Uz, Tolga et al. (2006) Impaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice. Neurosci Lett 393:23-6
Lugli, Giovanni; Larson, John; Martone, Maryann E et al. (2005) Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain-dependent manner. J Neurochem 94:896-905
Larson, John; Jessen, Ruth E; Kim, Daniel et al. (2005) Age-dependent and selective impairment of long-term potentiation in the anterior piriform cortex of mice lacking the fragile X mental retardation protein. J Neurosci 25:9460-9

Showing the most recent 10 out of 11 publications