Mice lacking the adenosine a, receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Using mice with a targeted disruption of the adenosine A, receptor (AIR), we examined the role of A(1)Rs in hippocampal long-term potentiation (LTP), long-term depression (LTD), and memory formation. Recordings from the Shaffer collateral-CA1 pathway of hippocampal slices from adult mice showed no differences between theta burst and tetanic stimulation-induced LTP in adenosine A, receptor knockout (A(1)R(-/-)), heterozygote (A(1)R(+/-)), and wildtype (A(1)R(+/+)) mice. However, paired pulse facilitation was impaired significantly in A1R(-/-) slices as compared to A1R(+/+) slices. LTD in the CA1 region was unaffected by the genetic manipulation. The three genotypes showed similar memory acquisition patterns when assessed for spatial reference and working memory in the Morris water maze tasks at 9 months of age. However, 10 months later A1R(-/-) mice showed some deficits in the 6-arm radial tunnel maze test. The latter appeared, however, not due to memory deficits but to decreased habituation to the test environment. Taken together, we observe normal spatial learning and memory and hippocampal CA1 synaptic plasticity in adult adenosine AIR knockout mice, but find modifications in arousal-related processes, including habituation, in this knockout model. (c) 2005 Wiley-Liss, Inc.