Abnormal hippocampal functional network and related memory impairment in pilocarpine-treated rats.

OBJECTIVE

Although abnormal hippocampal structure and impaired spatial memory have been revealed in a pilocarpine rat model of temporal lobe epilepsy (TLE), the brain functional network changes are still unclear. The aim of the present study was to investigate the changes of brain functional connectivity related to the hippocampus and the associated memory impairment in a pilocarpine model of TLE.

METHODS

Functional magnetic resonance imaging signals were recorded in pilocarpine-treated rats and controls by using a 7.0 T magnetic resonance scanner, and independent component analysis was performed to determine the hippocampal functional network. Behavioral tests, including novel location test, novel object test, and episodic memory test, were utilized to evaluate different aspects of memory impairment.

RESULTS

Memory impairment was observed in the TLE group in all three behavior tests. As compared to control, decreased connectivity of the hippocampal functional network was observed in the anterior dorsal hippocampus, the amygdala, the thalamus, the motor cortex, and the somatosensory cortex in the TLE group. Meanwhile, increased connectivity was found in the visual cortex, the mesencephalon, and the insula in the TLE group. Correlation analysis revealed that functional connections between the hippocampal network and brain regions such as the dorsal hippocampus and the thalamus specifically relate to the spatial memory behavior, whereas connections between the hippocampal network and regions such as the amygdala, the motor cortex, the somatosensory cortex, and the mesencephalon relate to both the spatial and the object memory performance.

SIGNIFICANCE: Our results indicated a trend of decreased connectivity in the hippocampal functional network, as well as spatial, object, and episodic memory impairment in the pilocarpine-induced TLE rat. Moreover, connections within the hippocampal network showed a relationship with spatial memory, and connections between the hippocampal network and regions in other networks revealed an association with both spatial and object memory.