Effects of Blocking Multiple Sources of Calcium in Hippocampus During Spatial Learning and Memory Using a Rapid Acquisition Variant of the Morris Water Task

Abstract

Long-term potentiation (LTP) is proposed to be the molecular mechanism underlying learning and memory in the brain. A key event for LTP is the influx of calcium into post-synaptic neurons via multiple ion channel control systems. One such system involves N-methyl-D-aspartate receptors (NMDARs), which were originally believed to be essential for LTP and new learning. Recent studies have demonstrated that hippocampal NMDARs are critical for learning new spatial information in a novel environment; however, when pre-training occurs prior to new spatial learning, these receptors are not needed. Additionally, researchers have shown that activation of voltage-gated calcium channels (VGCCs) and their associated calcium influx can induce LTP independent of NMDARs. These findings led to the idea that the amount of calcium required for learning in hippocampus depends on whether the new learning takes place in a novel or familiar environment, with a novel environment demanding greater calcium influx. It was hypothesized that to impair new learning in a familiar environment both NMDARs and VGCCs would need to be blocked. Long-Evans rats were trained in a three-phase version of the Morris water task, which included pre-training, new learning mass-training, and a probe test. Prior to mass-training, intrahippocampal VGCCs were blocked individually or in combination with NMDARs blockade to evaluate their effects on the rats learning and memory. The results showed that blocking both NMDARs and VGCCs simultaneously impaired new spatial learning with familiar information, whereas VGCC blockade alone did not.