Silvio O. Conte Centers for Interdisciplinary Research on Brain, Behavior, and Mental Health (P50): Regulation of In Vivo Synaptic Plasticity via the Dopamine/cAMP Signaling Pathway
The Conte Center has the objective of testing the hypothesis that aberrant dopamine (DA) signaling along the cAMP pathway contributes to ADHD. Project 3 serves multiple duties in achieving the overall objective. The research will link ADHD genetic targets to measures of in vivo memory-related synaptic plasticity. Viral vectors expressing small interfering RNA (siRNA) will be used to knockdown selected targets within the DA/cAMP pathway to examine their contribution to in vivo synaptic plasticity. Project 3 also will serveas the testing ground for the siRNA techniques and will determine the efficacy of particular siRNA targets suggested by Projects 1 & 2. The successfully developed techniques and best siRNA targets will then be applied in Project 4 using non-human primates. Thus, the well characterized synaptic plasticity measures in mice will be used to determine siRNA targets in the DA/cAMP pathway, and the most successful techniques and targets will be passed along to Project 4 for use in monkeys.
Relevance of the project to IDDRC mission:
The project examines memory mechanism in mice arising from aberrant dopamine (DA) signaling along the cAMP pathway. The work is guided by genetic defects that underlie Attention Deficit, Hyperactive Disorder (ADHD). Thus, the work is directly relevant to the mission of understanding dysfunction that contributes to developmental and retardation neural dysfunction.