Association rules for rat spatial learning: the importance of the hippocampus for binding item identity with item location.

Three cohorts of rats with extensive hippocampal lesions received multiple tests to examine the relationships between particular forms of associative learning and an influential account of hippocampal function (the cognitive map hypothesis). Hippocampal lesions spared both the ability to discriminate two different digging media and to discriminate two different room locations in a go/no-go task when each location was approached from a single direction. Hippocampal lesions had, however, differential effects on a more complex task (biconditional discrimination) where the correct response was signaled by the presence or absence of specific cues. For all biconditional tasks, digging in one medium (A) was rewarded in the presence of cue C, while digging in medium B was rewarded in the presences of cue D. Such biconditional tasks are "configural" as no individual cue or element predicts the solution (AC+, AD-, BD+, and BC-). When proximal context cues signaled the correct digging choice, biconditional learning was seemingly unaffected by hippocampal lesions. Severe deficits occurred, however, when the correct digging choice was signaled by distal room cues. Also, impaired was the ability to discriminate two locations when each location was approached from two directions. A task demand that predicted those tasks impaired by hippocampal damage was the need to combine specific cues with their relative spatial positions ("structural learning"). This ability makes it possible to distinguish the same cues set in different spatial arrays. Thus, the hippocampus appears necessary for configural discriminations involving structure, discriminations that potentially underlie the creation of cognitive maps.

What does spatial alternation tell us about retrosplenial cortex function?

The retrosplenial cortex supports navigation, but there are good reasons to suppose that the retrosplenial cortex has a very different role in spatial memory from that of the hippocampus and anterior thalamic nuclei. For example, retrosplenial lesions appear to have little or no effect on standard tests of spatial alternation. To examine these differences, the current study sought to determine whether the retrosplenial cortex is important for just one spatial cue type (e.g., allocentric, directional or intra-maze cues) or whether the retrosplenial cortex helps the animal switch between competing spatial strategies or competing cue types. Using T-maze alternation, retrosplenial lesion rats were challenged with situations in which the available spatial information between the sample and test phases was changed, so taxing the interaction between different cue types. Clear lesion deficits emerged when intra- and extra-maze cues were placed in conflict (by rotating the maze between the sample and choice phases), or when the animals were tested in the dark in a double-maze. Finally, temporary inactivation of the retrosplenial cortex by muscimol infusions resulted in a striking deficit on standard T-maze alternation, indicating that, over time, other sites may be able to compensate for the loss of the retrosplenial cortex. This pattern of results is consistent with the impoverished use of both allocentric and directional information, exacerbated by an impaired ability to switch between different cue types.

Calcium-binding protein immunoreactivity in Gudden's tegmental nuclei and the hippocampal formation: differential co-localization in neurons projecting to the mammillary bodies.

The principal projections to the mammillary bodies arise from just two sites, Gudden's tegmental nuclei (dorsal and ventral nuclei) and the hippocampal formation (subiculum and pre/postsubiculum). The present study sought to compare the neurochemical properties of these mammillary body inputs in the rat, with a focus on calcium-binding proteins. Neuronal calretinin (CR) immunoreactivity was sparse in Gudden's tegmental nuclei and showed no co-localization with neurons projecting to the mammillary bodies. In contrast, many of the ventral tegmental nucleus of Gudden cell that project to the mammillary bodies were parvalbumin (PV)-positive whereas a smaller number of mammillary inputs stained for calbindin (CB). Only a few mammillary body projection cells in the dorsal tegmental nucleus of Gudden co-localized with PV and none co-localized with CB. A very different pattern was found in the hippocampal formation. Here, a large proportion of postsubiculum cells that project to the mammillary bodies co-localized with CR, but not CB or PV. While many neurons in the dorsal and ventral subiculum projected to the mammillary bodies, these cells did not co-localize with the immunofluorescence of any of the three tested proteins. These findings highlight marked differences between hippocampal and tegmental inputs to the rat mammillary bodies as well as differences between the medial and lateral mammillary systems. These findings also indicate some conserved neurochemical properties in Gudden's tegmental nuclei across rodents and primates.