Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the dorsal hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.The consolidation of memories into their long-term, stabilized form is a topic of considerable theoretical and empirical scientific inquiry (McGaugh 2000;Squire et al. 2004;Frankland and Bontempi 2005;Wiltgen et al. 2005a). Independent brain circuits underlie different forms of memory, and, within a particular memory domain, the contribution of a specific region may depend upon the age of that memory (Ribot 1882;Squire 1992;Knowlton and Fanselow 1998;Frankland and Bontempi 2005).Consolidation theory suggests that memories are gradually reorganized such that the brain regions responsible for the storage/retrieval of a memory are changed (Marr 1971;McClelland et al. 1995;Squire and Alvarez 1995). Early evidence for this came from the characteristic pattern of temporally graded retrograde amnesia for declarative memories in human patients who had suffered insult to the medial temporal lobe (e.g., Scoville and Milner 1957). Similar patterns have been observed in animals using more circumscribed manipulations of the hippocampus across a variety of procedures, including object discrimination (Zola-Morgan and Squire 1990), contextual fear conditioning (Kim and Fanselow 1992;Anagnostaras et al. 1999), trace eyeblink conditioning (Kim et al. 1995;Takehara et al. 2002), and social transmission of food preference (Clark et al. 2002).In recent years, a shift has occurred toward identifying extrahippocampal regions that support long-term memories, and the medial prefrontal cortex (mPFC) has been implicated. The hippocampus and mPFC are functionally interrelated through correlated activity patterns that may be important for memory consolidation ( We assessed the role of the dorsal hippocampus (DH) and mPFC in trace and contextual fear memories. DH involvement in both trace and contextual fear conditioning has been previously demonstrated (e.g., McEchron et al. 1998;Quinn et al. 2002Quinn et al. , 2005Chowdhury et al. 2005). While a temporally graded retrograde amnesia for contextual fear conditioning is well established (e.g., Kim and Fanselow 1992;Anagnostaras et al. 1999), a similar assessment of trace fear conditioning has not yet been made. This experiment allows us to assess temporal gradients for two hippocampus-dependent memories within the same animal and determine whether the mPFC serves as a permanent storage/retrieval site for t...
The dorsal hippocampus (DH) is critically involved in the acquisition and expression of trace and contextual fear conditioning. NMDA/glutamate receptor-mediated transmission is thought to be one mechanism mediating the plastic changes that support long-term memories in the DH. However, their precise involvement in acquisition and expression processes has not been defined. To examine this issue, the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV; 10 microg/microl; 0.5 microl), was infused into the DH prior to conditioning and/or testing, using a trace fear conditioning procedure. All rats were tested for freezing to both tone and context in separate, counterbalanced sessions. The three sessions (1 training and 2 test) were separated by approximately 24 h. Using this design, it was possible to assess the role for DH NMDA receptors in the acquisition versus expression of trace and contextual fear conditioning. APV disrupted acquisition, but not expression, of contextual fear conditioning. By contrast, APV attenuated both acquisition and expression of trace fear memories. Thus, DH NMDA receptors appear to contribute to retrieval of some, but not all, fear memories.
The hippocampus is important for the formation of spatial, contextual, and episodic memories. For instance, lesions of the dorsal hippocampus (DH) produce demonstrable deficits in contextual fear conditioning. By contrast, it is generally agreed that the DH is not important for conditioning to a discrete cue (such as a tone or light) that is paired with footshock in a temporally contiguous fashion (delay conditioning). There are, however, some reports of hippocampus involvement in delay conditioning. The present series of experiments was designed to assess the conditions under which the hippocampus-dependent component of delay fear conditioning performance may be revealed. Here, we manipulated the number of conditioning trials and the intensity of the footshock in order to vary the strength of conditioning. The results indicate that the DH contributes to freezing performance to a delay conditioned tone when the conditioning parameters are relatively weak (few trials or low footshock intensity), but not when strong parameters are used. The results are discussed in terms of two parallel memory systems: a direct tone-footshock association that is independent of the hippocampus and a hippocampus-dependent memory for the conditioning session.
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