Abstract WP279: Disruption of Cortico-hippocampal Functional Connectivity Underlies the Memory Impairment Following Experimental Stroke

Abstract

Introduction: The cognitive consequences and the underlying mechanisms leading to cognitive impairments after cerebrovascular occlusive diseases are still unclear. Previously we have shown that distal middle cerebral artery occlusion (dMCAO) led to hippocampal hypofunction and spatial memory impairment in the absence of direct hippocampal injury. Hypothesis: In light of the importance of interactions between the cortex and hippocampus during memory processing, we hypothesize that cortical stroke disrupts afferent excitatory input from the lesioned cortical area to other remote brain regions such as the hippocampus, which can be mimicked by pharmacological inactivation of the cortex. Methods: Adult male rats were subjected to either dMCAO or cortical inactivation with AMPA receptor antagonist CNQX, compared to controls by sham-operation or injection with artificial CSF, respectively. Hippocampal function was determined by the social transmission of food preference (STFP) test, activity mapping by Fos imaging and in vivo electrophysiology by multi-channel extracellular recording. Results: dMCAO and cortical inactivation both induced impaired memory performance as measured in the STFP task and reduced hippocampal activation. The memory impairment was not attributed to change in olfaction by stroke or inactivation, since it was not detected in either experimental group. An increase in the bursts of sharp-wave associated ripples (SPW-Rs) was detected during reperfusion after stroke and after CNQX injection. Further, cortical inactivation also induced a shift of the theta phase, suggesting an alteration in the dynamics of hippocampal-cortical interactions. Conclusions: Given the crucial role of hippocampal theta and SPW-Rs in memory function, our results suggest that cortical stroke leads to memory impairment by disrupting the functional connectivity between the cortex and hippocampus, albeit without causing direct injury to the latter.