Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse

Abstract

The extent of the infrapyramidal mossy fiber projection in CA3 (IIP-MF) at the midseptotemporal level correlates negatively with two-way avoidance learning and positively with performance in the radial maze, both tasks known to be sensitive to hippocampal lesions. If hippocampal structural variations are causing behavioral variations, one must predict positive correlations between the extent of the IIP-MF and performance in swimming navigation. Thus, the authors studied learning and reversal learning of swimming navigation in mice in which the size of the IIP-MF had been randomized by means of systematic crosses and in 2 mouse strains known for differential infrapyramidal projections (C57BL/6 and DBA/2). In 19 random-bred mice (9 male, 10 female), the extent of the IIP-MF showed negative correlations with swimming time after platform reversal (day 4: r = -0.50, P < .03; day 5 r = -0.73, P < .001), but none during acquisition of the task. In addition, statistical analysis suggested an influence of asymmetrically distributed mossy fiber projections during reversal learning. The strain comparison between 18 DBA/2 and 16 C57BL/6 male mice confirmed these results: no strain difference during days 1-3, and a significantly faster swimming time in the strain C57BL/6 (with large IIP-MF) at day 5 (second day of reversal), associated with significantly more crossings of the former platform location during the early phases of reversal learning. This latter measure was also negatively correlated with asymmetry of the IIP-MF in both strains. Finally, variations of the IIP-MF were correlated partially with adjustment of swimming speed that appeared to depend on size and asymmetry of CA4 as well. Thus, natural variations in the size of the IIP-MF distribution, and, perhaps, of CA4, appear to linearly influence processes directly involved in complex spatial learning.

Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: Transgenic rescue and interactions with gene background

“…First, mutant 129B6(N3) mice, but not mutant 129B6(N9) mice, exhibited a significant elevation in hippocampal PKC expression relative to wild-type controls. Second, wild-type 129B6(N3) mice exhibited significant IP-MF hypoplasia relative to both inbred C57BL͞6J and wildtype 129B6(N9) mice, which is consistent with the 129Sv phenotype (2), and likely contributed to their spatial-reversal learning impairment (16). Conversely, mutant 129B6(N3) mice exhibited IP-MF hyperplasia relative to wild-type controls, which may be secondary to reductions in MARCKS expression during development and may not have been observable in mutant 129B6(N9) mice because of the already near maximal IP-MF limb length.…”

Dissecting the behaviour of transgenic mice: is it the mutation, the genetic background, or the environment?

“…In fact, we (Schoepke et al 1991;Bernasconi-Guastalla et al 1994;Wolfer et al 1997) and others (Upchurch & Wehner, 1988;Paylor et al 1993Paylor et al , 1994Klapdor & van der Staay, 1996;Montkowski et al 1997;Owen et al 1997;Crawley et al 1997;Balogh et al 1999) have found marked differences between inbred strains with respect to their ability to learn the Morris swimming navigation test. We have also observed clear differences between individuals of genetically heterogeneous populations (Schoepke et al 1991;Bernasconi-Guastalla et al 1994). Because performance in the Morris test varies considerably within samples of genetically homogeneous mice, one must assume that it is also strongly influenced by environmental factors.…”

Nicotine withdrawal disrupts both foreground and background contextual fear conditioning but not pre-pulse inhibition of the acoustic startle response in C57BL/6 mice

“…Whereas different substrates may be involved in the two types of conditioning, background and foreground conditioning do involve some common neural substrates. For example, DBA/2J mice, which have reduced levels of hippocampal protein kinase C (PKC) activity [22,83] and altered hippocampal mossy fiber projections [12,33,71] relative to other inbred mouse strains, show deficits in learning regardless of whether the context is a foreground or a background stimulus [60]. In addition, hippocampal lesions disrupt both foreground and background fear conditioning [5,43,51,61].…”

“…In addition, deficits in PPI have been reported in DBA/2J mice during withdrawal from chronic nicotine [72]. However, DBA/2J mice have altered hippocampal structure and function compared to other mouse strains [12,22,33,71,83] and thus the effects of nicotine withdrawal on hippocampal processes may differ between DBA/2J mice and other strains that do not show the same hippocampal deficits, such as C57BL/6 mice. Furthermore, it is unknown if the same treatment that produces nicotine withdrawal deficits in contextual fear conditioning in C57BL/6 mice would also produce deficits in PPI or startle responding.…”