Remodeling of hippocampal mossy fibers is selectively induced seven days after the acquisition of a spatial but not a cued reference memory task

Abstract

Relating storage of specific information to a particular neuromorphological change is difficult because behavioral performance factors are not readily disambiguated from underlying cognitive processes. This issue is addressed here by demonstrating robust reorganization of the hippocampal mossy fiber terminal field (MFTF) when adult rats learn the location of a hidden platform but not when rats learn to locate a visible platform. Because the latter task requires essentially the same behavioral performance as the former, the observed MFTF growth is seen as the consequence of specific input-dependent hippocampal activity patterns selectively generated by processing of extramaze but not intramaze cues. Successful performance on the hidden platform task requires formation of spatial memory. Increased MFTFs in hidden platform-trained rats are observed 7 d but not 2 d after training nor in swim controls. These results suggest that structural plasticity of the mossy fiber:CA3 circuit may contribute to the maintenance of long-lasting memory but not to the initial storage of the spatial context. Does gross remodeling of anatomical circuits contribute to longterm memory storage? It has long been thought that the act of learning redefines the physical structure of neural connections (e.g., Ramon y Cajal 1905); however, there are few experimental demonstrations of such rearrangements.Recently our group has provided direct evidence of learningdependent structural plasticity by demonstrating that training rats from two different strains (Holahan et al. 2006(Holahan et al. , 2007 to locate a hidden platform in a water maze induces growth of hippocampal granule cell mossy fiber terminal fields (MFTFs) from the stratum lucidum (SL) of CA3 into the stratum oriens (SO) and stratum pyramidale (SP). No growth was observed in swim controls that spent an equivalent period of time in the water maze as trained animals but with no platform present. When mice were trained in the same task no such growth was observed (Rekart et al. 2007).The presence of hippocampal MFTF growth after spatial training in rats is convergent with data from lesion studies in rats (Morris et al. 1982;Sutherland et al. 1983;Moser et al. 1993Moser et al. , 1995 and mice (Logue et al. 1997), which suggests that spatial learning tasks, such as locating a hidden platform, are mediated by the hippocampus (O'Keefe and Nadel 1978;Eichenbaum 2000). Thus, it seems likely that growth of the mossy fibers consequent to spatial learning is driven by spatial learningdependent hippocampal activity.One outstanding issue, however, is whether the learningdependent growth is truly specific for spatial (i.e., hippocampaldependent) learning, an issue raised in the original observations of Ramirez-Amaya et al. (1999. Although no growth was observed in swim control animals that were exposed to an equal amount of time in the pool as hidden platform-trained rats, swim controls, in contrast to trained animals, had no control over the amount of time spent in the pool. Indeed, the most reinf...

Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

“…To the best of our knowledge, very few studies have examined the influence of spatial learning on structural plasticity in this brain area. An increase in spine density within the molecular layer (44) and a sprouting of the mossy fiber sprouting within the CA3 subfield (45,46) are consistent with the effects reported here.…”

Ventral striatal plasticity and spatial memory

“…In this study we demonstrate that the molecular processes regarded as crucial for long-term stabilization of information are needed within this structure for spatial but not cue learning. This dissociation is similar to what is observed in the hippocampus (40). However, differently from the hippocampus, VS manipulations also impair responding to cues in auto-shaping, in Pavlovian-instrumental transfer, or in the early stages of instrumental conditioning, coherently with the high number of reward-responding neurons in this structure but not in the hippocampus (41).…”

Is memory consolidation a multiple-circuit system?

“…In this regard, it has been demonstrated that morphological rearrangements of dendrite spines and axonal redistribution in the hippocampus and cortex could occur after a variety of learning experiences (17). Accordingly, it has been demonstrated that axonal rearrangements in the mossy fibers of the hippocampus take place after several days of spatial water maze learning (11). However, these axonal rearrangements were not seen when animals were submitted to response implicit cue learning (11).…”

“…Accordingly, it has been demonstrated that axonal rearrangements in the mossy fibers of the hippocampus take place after several days of spatial water maze learning (11). However, these axonal rearrangements were not seen when animals were submitted to response implicit cue learning (11). In other words, the axonal rearrangement was seen only when animals consolidated explicit but not implicit spatial memory components.…”

“…Thus, the STM remains as long as these cascades are active, but for LTM transduction signals are carried to the nucleus where transcription factors are activated, which in turn leads to RNA translation into protein synthesis (11). These proteins account for cellular plastic changes that are considered the cellular correlations of stable LTM traces, i.e., the cellular counterparts of consolidation.…”