An essential role for retinoid receptors RAR beta and RXR gamma in long-term potentiation and depression

Hippocampal long-term potentiation (LTP) and longterm depression (LTD) are the most widely studied forms of synaptic plasticity thought to underlie sp atial learning and memory. We report here that RAR beta deficiency in mice virtually eliminates hippocampal CA1 LTP and LTD. It also results in substa ntial performance deficits in spatial learning and memory tasks. Surprising ly, RXR gamma null mice exhibit a distinct phenotype in which LTD is lost w hereas LTP is normal. Thus, while retinoid receptors contribute to both LTP and LTD, they do so in different ways. These findings not only genetically uncouple LTP and LTD but also reveal a novel and unexpected role for vitam in A in higher cognitive functions.