Impaired conditioned emotional response and object recognition are concomitant to neuronal damage in the amygdala and perirhinal cortex in middle-aged ischemic rats

Abstract

The current study characterizes fear conditioning responses following global ischemia and evaluates neuronal damage affecting discrete extra-hippocampal areas susceptible to contribute to post ischemic emotional and memory impairments. Conditioned emotional response, Barnes Maze and object recognition tests were used to assess emotional, spatial and recognition memory, respectively. Behavioural testing was initiated in middle-aged animals (10-12 month old) 1 week following sham (n=16) or 4VO occlusion (n=18). Post-mortem cellular assessment was performed in the hippocampal CA1 layer, the perirhinal cortex and basolateral amygdala. Middle-aged ischemic animals showed impaired spatial memory in the initial three testing days in the Barnes Maze and deficit in recognition memory. Of interest, ischemic rats demonstrated a significant reduction of freezing and increased locomotion during the contextual fear testing period, suggesting reduced fear in these animals. Assessment of neuronal density 40 days following global ischemia revealed that CA1 neuronal injury was accompanied by 20-25% neuronal loss in the basolateral nucleus of the amygdala and perirhinal cortex in middle-aged ischemic compared to sham-operated animals. This study represents the first demonstration of altered conditioned fear responses following ischemia. Our findings also indicate a vulnerability of extra-hippocampal neurons to ischemic injury, possibly contributing to discrete emotional and/or memory impairments post ischemia.