Environmental complexity affects contextual fear conditioning following hippocampal lesions in rats
ABSTRACT Contextual fear conditioning has become a benchmark measure for hippocampal function, even though several studies report successful acquisition in hippocampal-damaged rodents. The current study examined whether environmental complexity may account for these discrepancies. We directly compared single-session contextual fear conditioning in rats in a simple vs. complex environment. Hippocampal lesions led to reduced fear conditioning in both contexts, as measured by freezing, but the effect was significantly greater in the complex context. As well, lesions led to generalized fear when the complex context was paired with shock, but not when the simple context was paired. We suggest that the representation of the simple context formed by rats with hippocampal lesions was adequate to support associative learning, but the representation of the complex context, which depended to a greater extent on relational learning, was not. The results were interpreted as consistent with theories of hippocampal function that emphasize its role in integrating multiple stimulus elements in a memory trace.
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ABSTRACT: Previous work implicated the complement system in adult neurogenesis as well as elimination of synapses in the developing and injured central nervous system. In the present study, we used mice lacking the third complement component (C3) to elucidate the role the complement system plays in hippocampus-dependent learning and synaptic function. We found that the constitutive absence of C3 is associated with enhanced place and reversal learning in adult mice. Our findings of lower release probability at CA3-CA1 glutamatergic synapses in combination with unaltered overall efficacy of these synapses in C3 deficient mice implicate C3 as a negative regulator of the number of functional glutamatergic synapses in the hippocampus. The C3 deficient mice showed no signs of spontaneous epileptiform activity in the hippocampus. We conclude that C3 plays a role in the regulation of the number and function of glutamatergic synapses in the hippocampus and exerts negative effects on hippocampus-dependent cognitive performance.Experimental Neurology 12/2013; 253. DOI:10.1016/j.expneurol.2013.12.013 · 4.62 Impact Factor
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ABSTRACT: The present study sought to understand how the hippocampus and anterior thalamic nuclei are conjointly required for spatial learning by examining the impact of cutting a major tract (the fornix) that interconnects these two sites. The initial experiments examined the consequences of fornix lesions in rats on spatial biconditional discrimination learning. The rationale arose from previous findings showing that fornix lesions spare the learning of spatial biconditional tasks, despite the same task being highly sensitive to both hippocampal and anterior thalamic nuclei lesions. In the present study, fornix lesions only delayed acquisition of the spatial biconditional task, pointing to additional contributions from non-fornical routes linking the hippocampus with the anterior thalamic nuclei. The same fornix lesions spared the learning of an analogous nonspatial biconditional task that used local contextual cues. Subsequent tests, including T-maze place alternation, place learning in a cross-maze, and a go/no-go place discrimination, highlighted the impact of fornix lesions when distal spatial information is used flexibly to guide behaviour. The final experiment examined the ability to learn incidentally the spatial features of a square water-maze that had differently patterned walls. Fornix lesions disrupted performance but did not stop the rats from distinguishing the various corners of the maze. Overall, the results indicate that interconnections between the hippocampus and anterior thalamus, via the fornix, help to resolve problems with flexible spatial and temporal cues, but the results also signal the importance of additional, non-fornical contributions to hippocampal-anterior thalamic spatial processing, particularly for problems with more stable spatial solutions.Behavioural Brain Research 10/2014; 278. DOI:10.1016/j.bbr.2014.10.016 · 3.39 Impact Factor
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ABSTRACT: This review evaluates three current theories - Standard Consolidation (Squire & Wixted, 2011), Overshadowing (Sutherland, Sparks, & Lehmann, 2010), and Multiple Trace- Transformation (Winocur, Moscovitch, & Bontempi, 2010a) - in terms of their ability to account for the role of the hippocampus in recent and remote memory in animals. Evidence, based on consistent findings from tests of spatial memory and memory for acquired food preferences, favours the transformation account, but this conclusion is undermined by inconsistent results from studies that measured contextual fear memory, probably the most commonly used test of hippocampal involvement in anterograde and retrograde memory. Resolution of this issue may depend on exercising greater control over critical factors (e.g., contextual environment, amount of pre-exposure to the conditioning chamber, the number and distribution of foot-shocks) that can affect the representation of the memory shortly after learning and over the long-term. Research strategies aimed at characterizing the neural basis of long-term consolidation/transformation, as well as other outstanding issues are discussed.Neurobiology of Learning and Memory 10/2013; DOI:10.1016/j.nlm.2013.10.001 · 4.04 Impact Factor