Memory and long-term potentiation (LTP) dissociated: Normal spatial memory despite 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. Furthermore, in the last few years evidence has accumulated that dissociate the two. Because potassium channels might determine the weight of synapses in networks, we studied the role of Kv1.4, a presynaptic A-type voltage-dependent K+ channel, in both memory and LTP. Reverse transcription–PCR and Western blot analysis with specific antibodies showed that antisense oligodeoxyribonucleotide to Kv1.4 microinjected intraventricularly into rat brains obstructed hippocampal Kv1.4 mRNA, “knocking down” the protein in the hippocampus. This antisense knockdown had no effect on rat spatial maze learning, memory, or exploratory behavior, but eliminated both early- and late-phase LTP and reduced paired-pulse facilitation (a presynaptic effect) in CA1 pyramidal neurons without affecting dentate gyrus LTP. This presynaptic Kv1.4 knockdown together with previous postsynaptic Kv1.1 knockdown demonstrates that CA1 LTP is neither necessary nor sufficient for rat spatial memory.

Memory for object features versus memory for object location: a positron-emission tomography study of encoding and retrieval processes.

Regional cerebral blood flow was measured with positron-emission tomography during two encoding and two retrieval tasks that were designed to compare memory for object features with memory for object locations. Bilateral increases in regional cerebral blood flow were observed in both anterior and posterior regions of inferior temporal cortex and in ventral regions of prestriate cortex, when the condition that required retrieval of object locations was subtracted from the condition that required retrieval of object features. During encoding, these changes were less pronounced and were restricted to the left inferior temporal cortex and right ventral prestriate cortex. In contrast, both encoding and retrieval of object location were associated with bilateral changes in dorsal prestriate and posterior parietal cortex. Finally, the two encoding conditions activated left frontal lobe regions preferentially, whereas the two retrieval conditions activated right frontal lobe regions. These findings confirm that, in human subjects, memory for object features is mediated by a distributed system that includes ventral prestriate cortex and both anterior and posterior regions of the inferior temporal gyrus. In contrast, memory for the locations of objects appears to be mediated by an anatomically distinct system that includes more dorsal regions of prestriate cortex and posterior regions of the parietal lobe.