Wednesday, August 16, 2017

Electrolytic lesions of the dorsal hippocampus disrupt renewal of conditional fear after extinction

It has been recognized for decades that the expression of memory depends on the context in which memory is retrieved (). Contextual retrieval operates on both declarative memory in humans () and Pavlovian conditioning in animals (). And despite the importance of contextual retrieval in normal memory function, little is known concerning its brain mechanisms.
The hippocampus has a critical role in several memory processes, including episodic memory (for reviews, see ). Years ago it was suggested that the hippocampus has an important role in contextual memory retrieval (). Consistent with this view, an abundance of studies implicate the hippocampus not only in encoding contextual representations (), but also in using these representations in the service of memory retrieval (). We have recently shown in a series of experiments using intrahippocampal muscimol infusions that the dorsal hippocampus (DH) plays an important role in the context-dependent retrieval of fear memory in two different Pavlovian interference paradigms: latent inhibition () and extinction (Corcoran and Maren ). Both procedures yield context-dependent memory, insofar as conditional responding is low in the pre-exposure or extinction contexts and high outside of those contexts. Reversible inactivation of the DH prior to retrieval testing eliminates the renewal of fear to a CS outside of the pre-exposure or extinction context, without affecting fear expression per se or context discrimination.
Reversible lesions reveal an important role for the DH in the context specificity of latent inhibition and extinction. Earlier studies, however, using permanent hippocampal lesions found that electrolytic lesions of the fimbria/fornix () or neurotoxic lesions of the entire hippocampus () had no effect on the context-dependent expression of extinction. It may be the case that the nature (reversible vs. permanent) and timing (pre-training vs. pre-testing) of the lesions is an important determinant of their effects on the context dependence of extinction. Indeed, lesions and reversible inactivation may yield different behavioral outcomes, as other neural systems may compensate for irreversible damage, and the timing of hippocampal manipulation is critical in determining hippocampal deficits in contextual fear conditioning (). Thus, in the present study, we used Pavlovian fear conditioning in rats to examine the effects of electrolytic lesions made either before conditioning or after extinction on the context specificity of extinction. Because recent data suggest that the method for testing context-specific fear memory may affect hippocampal involvement in extinction (), we also examined the renewal of extinction either in a neutral context (Experiment 1) or in the conditioning context (Experiment 2). Our results reveal that electrolytic lesions of the DH disrupt the context dependence of extinction independent of when they are made relative to extinction, and independent of the context in which the renewal of extinguished fear is tested.


Experiment 1: Pre- or post-extinction dorsal hippocampal lesions and renewal testing in a neutral context

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