Contrasting the Amnesic Effects of Temporary Inactivation with Lesions of the Hippocampus on Context Memory

Abstract

Lesions and temporary inactivation of the hippocampus (HPC) in rodents occasionally lead to discrepant amnesic effects. We directly compared and contrasted the retrograde amnesic effects that small HPC lesions (~50% damage), large HPC lesions (~80% damage), and combined dorsal and ventral HPC inactivation using the sodium channel blocker tetrodotoxin (TTX) had on contextual fear conditioning. Compared to control rats, large HPC lesions significantly reduced freezing during retention testing, a behaviour consistent with retrograde amnesia. In contrast, neither the small lesions nor the TTX inactivation significantly reduced freezing. The extent of damage was significantly and negatively correlated with retention performance ( r (9) = -0.896, p < 0.001), suggesting that 70% or more of the HPC needed to be damaged to observe deficits. Importantly, TTX inactivation disrupted spatial memory in the Morris Water Task, confirming that our inactivation procedure did impair one form of HPC-dependent memory. To assess the extent of the TTX inactivation, immediate early gene expression was quantified in the HPC following the Morris Water Task. However, despite the behavioural impairment, we did not find a significant reduction in expression. We conclude that temporary inactivation of the HPC may fail to impair context fear memory because this technique does not sufficiently disrupt the HPC.