Sensorimotor stroke alters hippocampo-thalamic network activity

Abstract Many stroke survivors experience persisting episodic memory disturbances. Since hippocampal and para-hippocampal areas are usually spared from the infarcted area, alterations of memory processing networks remote from the ischemic brain region might be responsible for the observed clinical symptoms. To pinpoint changes in activity of hippocampal connections and their role in post-stroke cognitive impairment, we induced ischemic stroke by occlusion of the middle cerebral artery (MCAO) in adult rats and analyzed the functional and structural consequences using activity-dependent manganese (Mn 2+ ) enhanced MRI (MEMRI) along with behavioral and histopathological analysis. MCAO caused stroke lesions of variable extent along with sensorimotor and cognitive deficits. Direct hippocampal injury occurred in some rats, but was no prerequisite for cognitive impairment. In healthy rats, injection of Mn 2+ into the entorhinal cortex resulted in distribution of the tracer within the hippocampal subfields into the lateral septal nuclei. In MCAO rats, Mn 2+ accumulated in the ipsilateral thalamus. Histopathological analysis revealed secondary thalamic degeneration 28 days after stroke. Our findings provide in vivo evidence that remote sensorimotor stroke modifies the activity of hippocampal-thalamic networks. In addition to potentially reversible alterations in signaling of these connections, structural damage of the thalamus likely reinforces dysfunction of hippocampal-thalamic circuitries.