Research Awards
Reiko Maki Fitzsimonds, Ph.D.
Yale University School of Medicine
"Relationship between synaptic structure and plasticity in dendritic neuropathologies associate with Rett Syndrome"
2-Year Award: $100,000
Research Sponsor: The Farmer Family Foundation
Final Report (November 2005)
Brain cells communicate with each other and store information by modulating the efficiency or strength of electrical signals sent from one neuron to the next. In the laboratory it is possible to measure how "strong" the connections are using a variety of methods including recording the electrical signals (electrophysiology) as well as measuring the levels of proteins (biochemistry) that are necessary for allowing these electrical signals to pass from one neuron to the next. Using the brains from genetically engineered Mecp2-null mouse of Rett Syndrome, we performed electrophysiological and biochemical analyses to determine what, if any, changes occurred in neuronal communication in mice that were pre-symptomatic (young mice) versus those who exhibited motor and cognitive symptoms (older mice) that are very reminiscent to those observed in girls with Rett Syndrome. Interestingly, under baseline conditions, both younger and older Mecp2-null mice were indistinguishable from normal littermates. However, when neurons were challenged to respond to repetitive activity (thought to be analogous to learning) while the neurons of younger pre-symptomatic Mecp2-null mice were able to respond like their wild-type littermate control neurons, neurons from older, symptomatic Mecp2-null mice were impaired. Biochemically, we found that there are age-dependent abnormalities in the protein levels of a class of neurotransmitter receptors, the NMDA receptors, which are known to be critical for enabling neurons to change the strength of communication as a function of activity. NMDA receptors have been previously shown to be critical for some forms of learning and memory. The most interesting outcome of these studies however, is that many aspects of neuronal function are in fact preserved in the Mecp2-null mice, and that subtle and specific impairments in information encoding and storage may underlie myriad of neurological dysfunctions of Rett Syndrome.
Reiko Maki Fitzsimonds, Ph.D.Yale University School of Medicine
"Relationship between synaptic structure and plasticity in dendritic neuropathologies associate with Rett Syndrome"
2-Year Award: $100,000
Research Sponsor: The Farmer Family Foundation
Final Report (November 2005)
Brain cells communicate with each other and store information by modulating the efficiency or strength of electrical signals sent from one neuron to the next. In the laboratory it is possible to measure how "strong" the connections are using a variety of methods including recording the electrical signals (electrophysiology) as well as measuring the levels of proteins (biochemistry) that are necessary for allowing these electrical signals to pass from one neuron to the next. Using the brains from genetically engineered Mecp2-null mouse of Rett Syndrome, we performed electrophysiological and biochemical analyses to determine what, if any, changes occurred in neuronal communication in mice that were pre-symptomatic (young mice) versus those who exhibited motor and cognitive symptoms (older mice) that are very reminiscent to those observed in girls with Rett Syndrome. Interestingly, under baseline conditions, both younger and older Mecp2-null mice were indistinguishable from normal littermates. However, when neurons were challenged to respond to repetitive activity (thought to be analogous to learning) while the neurons of younger pre-symptomatic Mecp2-null mice were able to respond like their wild-type littermate control neurons, neurons from older, symptomatic Mecp2-null mice were impaired. Biochemically, we found that there are age-dependent abnormalities in the protein levels of a class of neurotransmitter receptors, the NMDA receptors, which are known to be critical for enabling neurons to change the strength of communication as a function of activity. NMDA receptors have been previously shown to be critical for some forms of learning and memory. The most interesting outcome of these studies however, is that many aspects of neuronal function are in fact preserved in the Mecp2-null mice, and that subtle and specific impairments in information encoding and storage may underlie myriad of neurological dysfunctions of Rett Syndrome.