This proposal seeks to understand the regulatory processes involved in mammalian synaptic plasticity. Specifically, the specific aims outlined in this research proposal will delineate the role of the pertussis toxin (PTX) sensitive G proteins in processes involved in hippocampus dependent long-term memory (LTM) and CAl late phase long-term potentiation (L-LTP) in the mouse. Pharmacological and genetic disruption of PTX-sensitive G proteins and the subsequent disruption of LTM and L-LTP will be the focus of the first and second specific aims. Since the PTX-sensitive 0 protein G1 provide the primary regulatory mechanism of adenylyl cyclase-mediated increases in cAMP, the third specific aim will center on studying the memory perturbations caused by excessive levels of this cyclic nucleotide. The fourth specific aim proposes to use pharmacological agents to reverse the LTM and L-LTP deficits caused by ablation of Gi protein function. Therefore, the conclusions from these studies will provide a better understanding of the aberrant signaling that lead to learning and memory deficits. Finally, based on unpublished data from our laboratory that implicate one of the pertussis toxin-sensitive G proteins as a possible cause for some forms of autism, an animal model may be derived from these studies to further understand the molecular basis of this human disorder.
| Wang, Hongbing; Ferguson, Gregory D; Pineda, Victor V et al. (2004) Overexpression of type-1 adenylyl cyclase in mouse forebrain enhances recognition memory and LTP. Nat Neurosci 7:635-42 |
| Pineda, Victor V; Athos, Jaime I; Wang, Hongbing et al. (2004) Removal of G(ialpha1) constraints on adenylyl cyclase in the hippocampus enhances LTP and impairs memory formation. Neuron 41:153-63 |
| Wang, Hongbing; Pineda, Victor V; Chan, Guy C K et al. (2003) Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long-term potentiation. J Neurosci 23:9710-8 |
| Athos, Jaime; Impey, Soren; Pineda, Victor V et al. (2002) Hippocampal CRE-mediated gene expression is required for contextual memory formation. Nat Neurosci 5:1119-20 |
