Recently, Anna Tyler and Gregory Holmes of the Department of Neurology discovered that changes in neural interaction within the hippocampus predict spatial memory deficits in status epilepticus (SE) rats. SE rats display similar damage to those found in human frontal lobe epilepsy.
Status epilepticus (SE), a common neurological emergency, is an epileptic seizure that lasts over 30 minutes. Caused by an injured hippocampus, SE can later facilitate the development of epilepsy, changes in behavior, and cognitive impairment. SE rats suffered significant loss of cells within three regions of their hippocampi.
Place cells–neurons linked with spatial memory–reside in the hippocampus. Each place cell is assigned to a spatial location in the environment and discharges signals with higher frequency as the rat approaches that location. These cells interact in a series of pyramidal functional networks as the rat navigates through its environment.
After inducing SE in one group with lithium and pilocarpine, Tyler and Holmes surgically fitted multiple electrodes into the CA1 region of the rats’ hippocampi to record their pyramidal neurons. The researchers plotted neural networks by recording ten or more neurons simultaneously. They then measured the rats’ spatial recognition by how accurately the rats completed a figure–eight maze after they had undergone training.
The SE rats performed significantly poorer than their control counterparts, and the researchers found that the SE rats’ neural networks fired simultaneously more frequently than their counterparts. The increased synchronization between pyramidal neurons correlated significantly with decreased spatial performance in the maze. Tyler and Holmes state in their research, “these results provide a physiological mechanism for SE-induced cognitive impairment and highlight the importance of the systems-level perspective in investigating spatial cognition.”
The researchers performed another experiment dealing with neural functions in SE rats between navigation and resting. Once resting, the rat’s place cells undergo a special phenomenon called replay, where the place cells repeat the firing patterns that initially occurred during navigation. Tyler and Holmes found replay essential to spatial memory reinforcement.
Researchers for the first time displayed disrupted replay in epileptic animals and correlated the phenomenon with a significant decrease in spatial memory. The pair calculated the percentage of neurons that maintained coordination between the two phases and found that a significantly less amount of neuron pairs retained their activity within SE rats. Only six percent of the SE rat’s neuron pairs maintained coordination in comparison to the fifteen percent displayed within the control.
The pair successfully applied the second order maximum entropy model previously applied in only in vitro and ex vivo, and their results also indicated the possible influence of non-place cells in spatial navigation.
Tyler, A. L., Mahoney, J. M., Richard, G. R., Holmes, G. L., Lenck-Santini, P., Scott, R. C. (2012). Functional network changes in hippocampal CA1 after status epilepticus predict spatial memory deficits in rats. The Journal of Neuroscience, 32(33), 11365-11376.