suppression of neurotoxic lesion-induced seizure activity evidence for a permanent role for the hippocampus in contextual memory抑制神经毒性发作lesion-induced证据一个永久的角色上下文记忆的海马.pdfVIP

Suppression of Neurotoxic Lesion-Induced Seizure Activity: Evidence for a Permanent Role for the Hippocampus in Contextual Memory 1 2 1 1 Fraser T. Sparks , Hugo Lehmann , Khadaryna Hernandez , Robert J. Sutherland * 1 Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, The University of Lethbridge, Lethbridge, Alberta, Canada, 2 Department of Psychology, Trent University, Peterborough, Ontario, Canada Abstract Damage to the hippocampus (HPC) using the excitotoxin N-methyl-D-aspartate (NMDA) can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity) during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA- induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX), a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA- induced, or no damage to the HPC at a recent (24 hours) or remote (5 weeks) time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the