Researchers Explore Spatial Memory with Stereo Investigator

The researchers quantified c-Fos positive cells in the CA1 region of the hippocampus. Image provided by Dr. Matthew Holahan.

The researchers quantified c-Fos positive cells in the CA1 region of the hippocampus. Image provided by Dr. Matthew Holahan.

Spacial memories help us navigate places like the office, the local coffee shop, or the supermarket. The hippocampus plays a key role in processing and recalling spacial memory, but as time passes, there is evidence that the anterior cingulate cortex (ACC) becomes more involved in recalling these memories. A recent paper published in PLOS ONE further investigates the ACC and found that taxing the hippocampus with spacial memory tasks accelerates the recruitment of the ACC for spacial memory recall.

The researchers divided 64 rats into 2 groups. One group was trained on one spacial memory task (water maze), and the other group was trained on two sequential spacial memory tasks (water maze and radial arm maze) to increase the demand on the hippocampus. Then, 8 days after the water maze training, 8 rats from each training group received an injection of muscimol, a GABA receptor agonist used to deactivate the ACC, and 8 rats from each group received an injection of saline. After receiving the injection of muscimol or saline, the rats were tested on their ability to navigate the water maze. This procedure was repeated with the remaining rats 37 days after water maze training.

There was a “substantial deficit” in test performance in the group trained on two spatial tasks, treated with muscimol, and tested at 37 days (a remote time point) compared to the control group (rats trained on two tasks, treated with saline, and tested at 37 days). This finding supports the hypothesis that the ACC is engaged more quickly when the hippocampus is taxed with spacial memory tasks. Rats treated with muscimol, trained on two spatial tasks, and tested at 8 days (a recent time point) displayed a “subtle deficit,” as did the group treated with muscimol, trained on just one spatial task, and tested at 37 days.

“The severely impaired performance in group WM/RAM:Remote:Muscimol supports the hypothesis that a remote spatial memory comes to rely more fully on neural ensembles in the ACC when distinct memories are sequentially encoded by overlapping neural ensembles in the hippocampus,” they say in their paper.

The researchers euthanized the rats and sectioned the brains to determine neuronal activity within the hippocampus. Using the Optical Fractionator probe in Stereo Investigator, they quantified cells labeled with c-Fos, an indicator of neuronal action, in the CA1 region of the hippocampus. They found higher levels of c-Fos positive cells in the hippocampi of rats who ran the water maze test 37 days (the remote time point) after training compared to rats who were tested 8 days after training.

“Because c-Fos labeling is often quite extensive both in the x-y and z-planes, it is difficult to get a reliable estimate of labeling by simply counting cells,” said Dr. Matthew Holahan, an author of the study. “With Stereo Investigator, we are able to get more reliable estimates of labeled cells in all planes, particularly, the z-plane which we are not able to get with other methods of analysis.”

The higher number of c-Fos positive cells in rats tested at the remote time point suggests that the hippocampus is continually involved in memory retrieval. And the behavioral tests indicate accelerated ACC involvement in spacial memory recall when the hippocampus is taxed.

Wartman, B.C., Gabel, J., Holahan, M.R. (2014) Inactivation of the Anterior Cingulate Reveals Enhanced Reliance on Cortical Networks for Remote Spatial Memory Retrieval after Sequential Memory Processing. PLoS ONE 9(10): e108711. doi:10.1371/journal.pone.0108711

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