Enhancement of encoding and retrieval functions through theta phase-specific manipulation of hippocampus.
Enhancement of encoding and retrieval functions through theta phase-specific manipulation of hippocampus.
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DOI：
10.7554/elife.03061
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发表时间：
2014-07-29
期刊：
影响因子：
7.7
通讯作者：
Wilson MA
中科院分区：
文献类型：
--
作者：
Siegle JH;Wilson MA
Assessing the behavioral relevance of the hippocampal theta rhythm has proven difficult, due to a shortage of experiments that selectively manipulate phase-specific information processing. Using closed-loop stimulation, we triggered inhibition of dorsal CA1 at specific phases of the endogenous theta rhythm in freely behaving mice. This intervention enhanced performance on a spatial navigation task that requires the encoding and retrieval of information related to reward location on every trial. In agreement with prior models of hippocampal function, the behavioral effects depended on both the phase of theta and the task segment at which we stimulated. Stimulation in the encoding segment enhanced performance when inhibition was triggered by the peak of theta. Conversely, stimulation in the retrieval segment enhanced performance when inhibition was triggered by the trough of theta. These results suggest that processes related to the encoding and retrieval of task-relevant information are preferentially active at distinct phases of theta. DOI: http://dx.doi.org/10.7554/eLife.03061.001 Around 15 years ago, an imaging study compared the brains of London taxi drivers—who need to know their way around one of the biggest cities in the world—with those of the general public, and found that a structure called the hippocampus was routinely larger in the taxi drivers. This finding was consistent with previous studies from rats, which showed that anatomical changes occur in the hippocampus after animals learn to navigate through various mazes. Together, these results suggest that the hippocampus is important for spatial awareness in both humans and rodents. The hippocampus—which takes its name from the Greek for ‘seahorse’ due to its shape—consists mostly of cells called pyramidal neurons, which communicate with one other using an excitatory molecule called glutamate. However, it also contains cells that suppress the activity of the pyramidal neurons, using an inhibitory molecule called GABA. When electrodes are used to record the combined electrical activity of many cells in the hippocampus—including both excitatory and inhibitory cells—the resulting pattern resembles a wave with peaks and troughs that repeat roughly eight times per second. Although this activity, known as the theta rhythm or cycle, has been observed in countless experiments, it has been difficult to pin down how it is relevant to behavior. Siegle and Wilson now show that the theta cycle may help the brain to keep incoming information separate from information stored in memory. This conclusion is based on the results of experiments on mice with hippocampi that had been modified to make them sensitive to light: in particular, light was needed to activate the neurons that suppress the activity of the pyramidal neurons. This meant that it was possible to reduce the overall level of activity in the hippocampus by shining light on certain neurons. The mice were trained to perform a spatial memory task that consisted of an encoding stage—where they learned the location of a reward—and a retrieval stage, in which they recalled this location from memory. On certain trials, pulses of light could be delivered to the brain at specific points in the theta cycle. Delivering light near the peak of the cycle during the encoding stage resulted in improved memory performance, as did delivering light near the trough of the cycle during the retrieval stage. These results suggest that the hippocampus preferentially encodes and retrieves information at different stages of the theta cycle. Specifically, activity just after the peak of the theta cycle is biased towards retrieval, meaning that reducing hippocampal activity at this time point will make it easier to form new memories. By contrast, reducing activity just after the trough of the theta cycle—when the hippocampus is biased towards encoding—will enhance memory retrieval. DOI: http://dx.doi.org/10.7554/eLife.03061.002
