title: Mice overexpressing type 1 adenylyl cyclase show enhanced spatial memory flexibility in the absence of intact synaptic long-term depression.
abstract: There is significant interest in understanding the contribution of intracellular signaling and synaptic substrates to memory flexibility, which involves new learning and suppression of obsolete memory. Here, we report that enhancement of Ca2+ -stimulated cAMP signaling by overexpressing type 1 adenylyl cyclase (AC1) facilitated long-term potentiation (LTP) but impaired long-term depression (LTD) at the hippocampal Shaffer collateral-CA1 synapses. However, following the induction of LTP, low-frequency stimulation caused comparable synaptic depotentiation in both wild type and AC1 transgenic (AC1 TG) mice. Although previous studies have suggested the function of LTD in spatial memory flexibility, AC1 TG mice showed not only better initial learning in the Morris water maze, but also faster acquisition and increased ratio of new memory formation to old memory retention during the reversal platform training. In the memory extinction test, which requires suppression of old memory without involving the acquisition of the new platform information, AC1 TG and wild type mice showed comparable performance. Our results demonstrate new functions of Ca2+ -stimulated AC1, and also suggest that certain aspects of hippocampus-dependent behavioral flexibility may not require intact LTD.
authors.affiliation: Department of Physiology, Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
mesh_terms: D000222:Adaptation, Physiological; D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1