Learning spatial orientation tasks in the radial-maze and structural variation in the hippocampus in inbred mice

Abstract

In the present paper we review a series of experiments showing that heritable variations in the size of the hippocampal intra- and infrapyramidal mossy fiber (IIPMF) terminal fields correlate with performance in spatial, but not non-spatial radial-maze tasks. Experimental manipulation of the size of this projection by means of early postnatal hyperthyroidism produces the effects predicted from the correlations obtained with inbred mouse strains. Although the physiological mechanisms behind these correlations are unknown as yet, several lines of evidence indicate that these correlations are causal.

Figure 1

Radial maze for use with mice. Plexiglas doors can be lowered to limit access to all arms simultaneously. From Crusio, 1999 [4], with permission.

Figure 2

Diagram of a Timm-stained cross-section of the hippocampus. The hippocampal subregion CA3-CA4 (the area of morphometry) is indicated in black, stippled and hatched areas. Black areas: suprapyramidal (SP), intra- and infrapyramidal (IIP) and hilar (CA4) mossy fiber terminal fields originating from the dentate gyrus. Stippled area: strata oriens (OR) and radiatum (RD). Hatched area: stratum lacunosum-moleculare (LM). CA1, subregion of the hippocampus without mossy fibers; FI, fimbria hippocampi; FD, fascia dentata; OL and ML, outer and middle molecular layers of the fascia dentata; SG, supragranular layer; GC, granular cells.

Figure 3

Means ± SEM of the sizes of the hippocampal intra- and infrapyramidal mossy fiber projection (IIPMF) and the numbers of errors committed in a simple radial-maze task, with free access to arms and all 8 arms containing a food reward, each dot representing the mean of one inbred strain. Hippocampal data are based on 4 male mice per strain, behavioral data are from 3 males per strain. Data taken from Crusio et al., 1987 [11].

Figure 4

Means ± SEM of the sizes of the hippocampal intra- and infrapyramidal mossy fiber projection (IIPMF) and the numbers of errors committed in a simple radial-maze task, with subjects confined to the central platform for 5 sec. in between subsequent arm choices and all 8 arms containing a food reward. Each dot represents the mean of one inbred strain. n = 6 male mice per strain. Data taken from Schwegler et al., 1990 [23].

Figure 5

Means ± SEM of the sizes of the hippocampal intra- and infrapyramidal mossy fiber projection (IIPMF) and the numbers of working-memory (WM) and reference memory (RM) errors committed in an 8-arm radial maze with only 4 arms containing a food reward. Animals were tested during 10 days, one trial per day. Numvbers of errors shown are cumulative error counts on days 3–10. Upper panels: Spatial task. Lower panels: Non-spatial task. Left panels: Working-memory errors. Right panels: Reference memory errors. Note the different scales in the upper and lower panels, the non-spatial task obviously being much easier for the subjects.

Figure 6

Means ± SEM of the sizes of the hippocampal intra- and infrapyramidal mossy fiber projection (IIPMF) and the numbers of errors committed in a simple radial-maze task, with free access to arms and all 8 arms containing a food reward, each dot representing the mean of one inbred strain. Data taken from Figure 4 (8 strain means) and from Refs. [30-33] (10 additional strain means). For clarity, SEMs have been omitted.