Spatial learning induces presynaptic structural remodeling in the hippocampal mossy fiber system of two rat strains

Abstract

Hebb (1949) proposed that after learning both presynaptic and postsynaptic structural changes form the neural substrate of long-lasting memory. Despite this, there are few instances linking presynaptic remodeling with learning. Here the authors demonstrate in two different rat strains that learning the location of a hidden platform induces expansion of the presynaptic hippocampal mossy fiber terminal field (MFTF) from the stratum lucidum to the distal stratum oriens (dSO). Prior to any training, Long Evans rats (LER) showed an extensive endogenous MFTF innervation of DSO, in contrast to Wistar rats (WR) that showed minimal innervation. LER showed better recall than WR on the hidden platform water maze task and a visible reversal water maze task. In both strains, significant MFTF expansion to dSO, spanning approximately 200 mum, was detected 7 days after training on the hidden platform task, but only LER showed significant MFTF expansion 24 h after training. It is attractive to think that the MFTF expansion to dSO contributes both to long-lasting memory formation and to facilitating spatial navigation strategies. The present results establish learning-induced axonal remodeling of the hippocampal MF system in adult rats as an especially useful system for exploring presynaptic morphological adjustments consequent to learning.

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

“…Moreover, the significant training-dependent increments in the SOSP of HIDDEN rats were restricted to the rostralmost third of the septal hippocampus ( Fig. 2A), a point emphasized by both Ramirez-Amaya et al (2001) and Holahan et al (2006).In rats sacrificed 48 h after training, the size and relative distribution of MFTFs did not differ as a function of training. Specifically, no significant effect of training on the size of the SOSP, the SL, or the SOSP/SL within the regio inferior was found (data not shown).…”

“…For example, rats with hippocampal lesions perform indistinguishably from sham controls when the location of the platform is clearly marked (Morris et al 1982;Save and Poucet 2000). Thus, if the observed learning-dependent changes in MFTFs are truly caused by hippocampal-dependent spatial learning (Holahan et al 2006), then the amount of hippocampal processing necessary should be increased during spatial processing relative to learning cued by a marked platform (Rudy et al 1987). The present study tests whether such processing differences will be reflected in alterations in MFTF organization.…”

“…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.…”

“…Animals were handled for 3-5 d prior to behavioral training. Training took place during the light cycle (between 10:00-17:00), and all animal use and care were in accordance with Northwestern University Center for Comparative Medicine guidelines.Rats were trained in the water maze similar to what has been described previously (Holahan et al 2006). One modification to the Holahan et al paradigm is that animals were randomly separated into three (rather than two) groups: In addition to those Cold Spring Harbor Laboratory Press on May 9, 2018 -Published by learnmem.cshlp.org Downloaded from trained to find a hidden platform (HIDDEN; 10 cm in diameter submerged 2 cm beneath surface of water; n = 7) and the swim control rats (SC; n = 7) that were yoked to HIDDEN rats and spent the same amount of time in the pool (without a platform) as that animal, there were rats trained to find a visible platform (VISIBLE; platform 3 cm above the surface of the water and marked by a yellow Styrofoam buoy tethered to the platform; n = 7).…”

“…Images were then coded and a point-counting grid (squares = 25 µm/side) was digitally superimposed. Grid intersections overlying dark Timm's silver precipitate were counted as belonging either to the SL or to the strata oriens and stratum pyramidale (SOSP) using described criteria (Holahan et al 2006). The areas for the SO and SP were combined as they are hard to distinguish, particularly proximal to CA3c (Claiborne et al 1986).…”