Impairments in Fear Extinction Memory and Basolateral Amygdala Plasticity in the TgF344-AD Rat Model of Alzheimer’s Disease Are Distinct from Nonpathological Aging

Abstract

AbstractFear-based disorders such as post-traumatic stress disorder (PTSD) steepen age-related cognitive decline and double the risk for developing Alzheimer’s disease (AD). Because of the seemingly hyperactive properties of fear memories, PTSD symptoms can worsen with age. Perturbations in the synaptic circuitry supporting fear memory extinction are key neural substrates of PTSD. The basolateral amygdala (BLA) is a medial temporal lobe structure that is critical in the encoding, consolidation, and retrieval of fear memories. As little is known about fear extinction memory and BLA synaptic dysfunction within the context of aging and AD, the goal of this study was to investigate how fear extinction memory deficits and basal amygdaloid nucleus (BA) synaptic dysfunction differentially associate in nonpathologic aging and AD in the TgF344AD (TgAD) rat model of AD. Young, middle-aged, and older-aged WT and TgAD rats were trained on a delay fear conditioning and extinction procedure beforeex vivoextracellular field potential recording experiments in the BA. Relative to young WT rats, long-term extinction memory was impaired, and in general, was associated with a hyperexcitable BA and impaired LTP in TgAD rats at all ages. In contrast, long-term extinction memory was impaired in aged WT rats and was associated with impaired LTP but not BA hyperexcitability. Interestingly, the middle-aged TgAD rats showed intact short-term extinction and BA LTP, which is suggestive of a compensatory mechanism, whereas differential neural recruitment in older-aged WT rats may have facilitated short-term extinction. As such, associations between fear extinction memory and amygdala deficits in nonpathologic aging and AD are dissociable.