The dorsal hippocampus is essential for context discrimination but not for contextual conditioning.

Abstract

The authors describe how (a) the timing of hippocampal lesions and (b) the behavioral-representational demands of the task affect the requirement for the hippocampus in contextual fear conditioning. Post- but not pretraining lesions of the hippocampus greatly reduced contextual fear conditioning. In contrast, pretraining lesions of the hippocampus abolished context discrimination, a procedure in which mice are trained to discriminate between 2 similar chambers (shock context vs. no-shock context). Whereas either contextual- or cue-based strategies can be used to recognize an aversive context, discrimination between similar contexts is optimally acquired by contextual (hippocampal)-based strategies. In keeping with the lesion results, Nf1(+/-)/Nmdar1(+/-) mutant mice, which have spatial learning deficits, are impaired in context discrimination but not in contextual conditioning. Together, these data dissociate hippocampal and nonhippocampal contributions to contextual conditioning, and they provide direct evidence that the hippocampus plays an essential role in the processing of contextual stimuli.

Cites (4)

1. Place navigation impaired in rats with hippocampal lesions
   Morris, R. G. M., Garrud, P., Rawlins, J. N. P., O'Keefe, J. · 1982 · Nature
2. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
   Phillips, R. G., LeDoux, J. E. · 1992 · Behavioral Neuroscience
3. Modality-Specific Retrograde Amnesia of Fear
   Kim, Jeansok J., Fanselow, Michael S. · 1992 · Science
4. Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task
   Logue, Sheree F., Paylor, Richard, Wehner, Jeanne M. · 1997 · Behavioral Neuroscience

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