Ontogeny and Neural Substrates of the Context Pre-exposure Facilitation Effect on Contextual Fear Conditioning

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2009-05
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The essential mnemonic role of the hippocampus in contextual fear conditioning has been reliably demonstrated in the intact adult rat, and is believed to emerge around post-natal day (PND) 23. The mnemonic role mediates the conjugation of the individual feature representations of the context into a unified conjunctive representation, which can then be associated with the reinforcer. However, there is evidence that conditioning at the PND 23-24 may be typically supported by a feature-based simple associative system (SAS) that is hippocampus-independent. To address this issue, a variant of contextual fear conditioning that favors utilization of the hippocampus-dependent configural associative system (CAS) while minimizing contributions from the hippocampus-independent SAS was implemented early in ontogeny. This variant, termed the context-preexposure-facilitation-effect-of-the-immediate-shock-deficit (CPFE-ISD), involves exposure to context and foot shock on successive occasions. After various training parameter manipulations, the ability for the hippocampus-dependent variant seems to emerge rapidly between PND 17 and PND 24, and continues to develop to PND 31. Additional evidence suggests the mnemonic function at PND 24 is mediated by hippocampal long-term potentiation as antagonism of NMDA-type glutamate receptors in the dorsal hippocampus with dizocilpine blocked conditioning in the variant paradigm. This ontogenetic profile of the CPFE-ISD parallels that for conventional context conditioning, suggesting common neural substrates may control conditioning in both paradigms. This is important because the behavioral and neural mechanisms of conventional context conditioning are more variable and controversial than of the CPFE-ISD. Previously mentioned support for SAS-mediated conditioning at PND 23-24 may have been due to the protracted development of the SAS-inhibitory function of the CAS, relative to the mnemonic function, which clearly emerges by PND 24.
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