Memory and long-term potentiation (LTP) dissociated: Normal spatial memorydespite CA1 LTP elimination with Kv1.4 antisense

Long-term potentiation (LTP) in the hippocampal slice preparation has been proposed as an in vitro model for long-term memory. However, correlation of LTP with memory in living animals has been difficult to demonstrate. Furth ermore, in the last few years evidence has accumulated that dissociate the two. Because potassium channels might determine the weight of synapses in n etworks, we studied the role of Kv1.4, a presynaptic A-type voltage-depende nt K+ channel, in both memory and LTP. Reverse transcription-PCR and Wester n blot analysis with specific antibodies showed that antisense oligodeoxyri bonucleotide to Kv1.4 microinjected intraventricularly into rat brains obst ructed hippocampal Kv1.4 mRNA, "knocking down" the protein in the hippocamp us. This antisense knockdown had no effect on rat spatial maze learning, me mory, or exploratory behavior, but eliminated both early- and late-phase LT P and reduced paired-pulse facilitation (a presynaptic effect) in CA1 pyram idal neurons without affecting dentate gyrus LTP. This presynaptic Kv1.4 kn ockdown together with previous postsynaptic Kv1.1 knockdown demonstrates th at CA1 LTP is neither necessary nor sufficient for rat spatial memory.