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

Hebb ( 1949 ) proposed that after learning both presynaptic and postsynaptic structural changes form the neural substrate oflong‐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 μm, 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. © 2006 Wiley‐Liss, Inc.

[1]  C. Broekkamp,et al.  Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory , 1995, Physiology & Behavior.

[2]  D. O. Hebb,et al.  The organization of behavior , 1988 .

[3]  J. Lassalle,et al.  Reversible Inactivation of the Hippocampal Mossy Fiber Synapses in Mice Impairs Spatial Learning, but neither Consolidation nor Memory Retrieval, in the Morris Navigation Task , 2000, Neurobiology of Learning and Memory.

[4]  D. Amaral,et al.  A light and electron microscopic analysis of the mossy fibers of the rat dentate gyrus , 1986, The Journal of comparative neurology.

[5]  M. Escobar,et al.  Synaptogenesis of mossy fibers induced by spatial water maze overtraining , 1999, Hippocampus.

[6]  S. Glickman,et al.  VISUAL CLIFF BEHAVIOR IN ALBINO AND HOODED RATS. , 1964, Journal of comparative and physiological psychology.

[7]  Vincenzo De Paola,et al.  AMPA receptors regulate dynamic equilibrium of presynaptic terminals in mature hippocampal networks , 2003, Nature Neuroscience.

[8]  F. Gaarskjaer,et al.  The development of the dentate area and the hippocampal mossy fiber projection of the rat , 1985, The Journal of comparative neurology.

[9]  H. Cline,et al.  Coordinated Motor Neuron Axon Growth and Neuromuscular Synaptogenesis Are Promoted by CPG15 In Vivo , 2005, Neuron.

[10]  Rafael Yuste,et al.  Bidirectional Regulation of Hippocampal Mossy Fiber Filopodial Motility by Kainate Receptors A Two-Step Model of Synaptogenesis , 2003, Neuron.

[11]  G. Holmes,et al.  Mossy fiber sprouting after recurrent seizures during early development in rats , 1999 .

[12]  Elizabeth Gould,et al.  Stress and hippocampal neurogenesis , 1999, Biological Psychiatry.

[13]  W. Cowan,et al.  An autoradiographic study of the organization of intrahippocampal association pathways in the rat , 1978, The Journal of comparative neurology.

[14]  B. McNaughton,et al.  Spatial selectivity of unit activity in the hippocampal granular layer , 1993, Hippocampus.

[15]  J. Altman,et al.  Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats , 1965, The Journal of comparative neurology.

[16]  E. Abel Response to alarm substance in different rat strains , 1992, Physiology & Behavior.

[17]  J. Lassalle,et al.  Analysis of behavioral and hippocampal variation in congenic albino and pigmented BALB mice , 1994, Behavior genetics.

[18]  S. Cohen-Cory,et al.  BDNF Modulates, But Does Not Mediate, Activity-Dependent Branching and Remodeling of Optic Axon Arbors In Vivo , 1999, The Journal of Neuroscience.

[19]  Chunmei Zhao,et al.  Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse Hippocampus , 2006, The Journal of Neuroscience.

[20]  V. Ramirez-Amaya,et al.  Spatial Long-Term Memory Is Related to Mossy Fiber Synaptogenesis , 2001, The Journal of Neuroscience.

[21]  I. Whishaw,et al.  Place and matching-to-place spatial learning affected by rat inbreeding (Dark–Agouti, Fischer 344) and albinism (Wistar, Sprague–Dawley) but not domestication (wild rat vs. Long–Evans, Fischer–Norway) , 2002, Behavioural Brain Research.

[22]  C Bucherelli,et al.  Spontaneous and conditioned behavior of Wistar and Long Evans rats. , 1987, Archives italiennes de biologie.

[23]  A Routtenberg,et al.  Rapid induction by kainic acid of both axonal growth and F1/GAP‐43 protein in the adult rat hippocampal granule cells , 1996, The Journal of comparative neurology.

[24]  C. Woolley,et al.  Estradiol increases the frequency of multiple synapse boutons in the hippocampal CA1 region of the adult female rat , 1996, The Journal of comparative neurology.

[25]  F. Gage,et al.  Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[26]  K. Tóth,et al.  Target-specific expression of presynaptic mossy fiber plasticity. , 1998, Science.

[27]  H. Kasai,et al.  Structure–stability–function relationships of dendritic spines , 2003, Trends in Neurosciences.

[28]  M. Frotscher,et al.  A hippocampal interneuron associated with the mossy fiber system. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Wim E Crusio,et al.  Hippocampal morphology and spatially related behavior in long‐evans and CFY rats , 1993, Hippocampus.

[30]  Kristen M Harris,et al.  Structural changes at dendritic spine synapses during long-term potentiation. , 2003, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[31]  H. Lipp,et al.  Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse , 1991, Hippocampus.

[32]  R. Palmiter,et al.  Ultrastructural localization of zinc transporter-3 (ZnT-3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[33]  B. Heimrich,et al.  Strain-specific correlations between hippocampal structural traits and habituation in a spatial novelty situation , 1987, Behavioural Brain Research.

[34]  H. Lipp,et al.  Hippocampal mossy fibers and swimming navigation in mice: Correlations with size and left‐right asymmetries , 1994, Hippocampus.

[35]  B. Heimrich,et al.  Infrapyramidal mossy fibers and two-way avoidance learning: developmental modification of hippocampal circuitry and adult behavior of rats and mice , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  G Buzsáki,et al.  GABAergic Cells Are the Major Postsynaptic Targets of Mossy Fibers in the Rat Hippocampus , 1998, The Journal of Neuroscience.

[37]  M. Tessier-Lavigne,et al.  Stereotyped Pruning of Long Hippocampal Axon Branches Triggered by Retraction Inducers of the Semaphorin Family , 2003, Cell.

[38]  Wim E Crusio,et al.  Hippocampal mossy fibers and radial-maze learning in the mouse: A correlation with spatial working memory but not with non-spatial reference memory , 1990, Neuroscience.

[39]  C. Florian,et al.  Hippocampal CA3-region is crucial for acquisition and memory consolidation in Morris water maze task in mice , 2004, Behavioural Brain Research.

[40]  G. Banker,et al.  The expression and distribution of the microtubule-associated proteins tau and microtubule-associated protein 2 in hippocampal neurons in the rat in situ and in cell culture , 1987, Neuroscience.

[41]  Wim E Crusio,et al.  Hippocampal mossy fiber distribution covaries with open-field habituation in the mouse , 1987, Behavioural Brain Research.

[42]  D. Amaral,et al.  Development of the mossy fibers of the dentate gyrus: I. A light and electron microscopic study of the mossy fibers and their expansions , 1981, The Journal of comparative neurology.