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Sci. STKE, 13 January 2004
Vol. 2004, Issue 215, p. tw14
[DOI: 10.1126/stke.2152004TW14]


SYNAPTIC PLASTICITY Impaired Memory Despite Enhanced LTP

Synaptic plasticity associated with learning and memory is presently modeled on an enhancement of synaptic efficacy called long-term potentiation (LTP), which is known to involve cAMP signaling and protein kinase A (see Mansuy). Pineda et al. analyzed mice for the involvement of the G protein that inhibits adenylyl cyclase Gαi by pharmacologic inhibition or by genetic knockout (Gαi1–/–) or antisense oligonucleotide-mediated depletion of Gαi, each of which showed similar disruptions in memory formation in live animals. Administration of pertussis toxin to the CA1 region of the hippocampus of mice disrupted memory measured by two behavioral tests. The knockout mice were also impaired in several, but not all, tests of memory, which suggests specificity in the signaling pathways implicated in forming different types of memories. However, the homozygous and heterozygous mice had increased levels of adenylyl cyclase activity. Analysis of various forms of synaptic plasticity in the hippocampal regions of the knockout mice indicated that the mice formed late-phase (longer-lasting) LTP under stimulating conditions that in wild-type mice formed an early, decremental LTP. Thus, loss of tonic inhibition of adenylyl cyclase activity may result in enhanced synaptic efficacy, which occludes the ability to encode synapse activity-dependent information required for proper memory formation.

I. Mansuy, A constraint on cAMP signaling. Neuron 41, 4-6 (2004). [Online Journal]

V. V. Pineda, J. I. Athos, H. Wang, J. Celver, D. Ippolito, G. Boulay, L. Birnbaumer, D. R. Storm, Removal of Giα1 constraints on adenylyl cyclase in the hippocampus enhances LTP and impairs memory formation. Neuron 41, 153-163 (2004). [Online Journal]

Citation: Impaired Memory Despite Enhanced LTP. Sci. STKE 2004, tw14 (2004).

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