Using Fos imaging in the rat to reveal the anatomical extent of the disruptive effects of fornix lesions

Activity of the immediate early gene c-fos was compared across hemispheres in rats with unilateral fornix lesions. To engage Fos production, rats first performed a radial arm maze task that is severely disrupted by bilateral fornix lesions. Using immunohistochemical techniques, Fos-positive cells were visualized and counted in 39 sites in both hemispheres. Fornix lesions led to a significant reduction in Fos in all ipsilateral hippocampal subfields, as well as the entorhinal cortex and most of the subicular complex. Other sites that showed reduced activity included the ipsilateral retrosplenial, anterior cingulate, and postrhinal cortices. Subcortical regions showing significant Fos decreases included the anterior thalamic nuclei, supramammillary nucleus, diagonal band of Broca, and lateral septum. Thus, the effects of fornix lesions extended beyond the hippocampal formation and included sites not directly innervated by the tract. These changes were nevertheless selective, as shown by the lack of hemispheric difference in any of the preselected control sites, the perirhinal cortex, or nucleus accumbens. Furthermore, there were no hemispheric differences in an additional group of animals with unilateral fornix lesions that were killed directly from the home cage. The location of Fos changes closely corresponded to those brain regions that when lesioned disrupt spatial working memory. Moreover, there was a correspondence between those brain regions that show increased Fos production in normal animals performing the radial arm maze task and those affected by fornix lesions. These results show that fornix transection has widespread, but selective, effects on a network of structures normally activated by spatial memory processes, with these effects extending beyond the hippocampal formation

Fos imaging reveals differential patterns of hippocampal and parahippocampal subfield activation in rats in response to different spatial memory tests

We compared neuronal activation, as measured by Fos staining, during different spatial tasks in two experiments. The counts of Fos-stained neurons in the hippocampus increased as the spatial demands of the tasks increased, the tasks having been carefully matched for other factors. In Experiment 1, matched groups of rats either ran a standard eight-arm radial maze task or were trained to run up and down just one arm of the maze; the number of runs and rewards was identical in both conditions. In Experiment 2, rats were trained on the eight-arm maze but in different rooms. On the critical test day, both groups were run in the same room so that one group now performed with novel landmarks. All hippocampal subfields (dentate gyrus, CA3, CA1, dorsal, ventral, and caudal subiculum) showed a relative increases in c-fos activation in the eight-arm (Experiment 1) and novel room (Experiment 2) conditions, the sole exception being the ventral subiculum in Experiment 2. Although increased c-fosactivation was found in both dorsal and ventral hippocampus, in Experiment 2 the relative increase was significantly greater in the dorsal hippocampus. Parahippocampal cortices responded heterogeneously: the perirhinal cortex failed to show increased activation in both experiments, in contrast to the entorhinal and postrhinal cortices. Subsequent comparisons confirmed that the perirhinal and postrhinal cortices responded in qualitatively different ways, the perirhinal cortex differing from the rest of the hippocampal formation. These experiments, which provide the first analysis of hippocampal Fos production during tests of allocentric spatial working memory, reveal that all components of the hippocampus are activated, but that under certain conditions the dorsal hippocampus is disproportionately involved

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

Fos Imaging Reveals Differential Patterns of Hippocampal and Parahippocampal Subfield Activation in Rats in Response to Different Spatial Memory Tests

We compared neuronal activation, as measured by Fos staining, during different spatial tasks in two experiments. The counts of Fos-stained neurons in the hippocampus increased as the spatial demands of the tasks increased, the tasks having been carefully matched for other factors. In Experiment 1, matched groups of rats either ran a standard eight-arm radial maze task or were trained to run up and down just one arm of the maze; the number of runs and rewards was identical in both conditions. In Experiment 2, rats were trained on the eight-arm maze but in different rooms. On the critical test day, both groups were run in the same room so that one group now performed with novel landmarks. All hippocampal subfields (dentate gyrus, CA3, CA1, dorsal, ventral, and caudal subiculum) showed a relative increases in c-fos activation in the eight-arm (Experiment 1) and novel room (Experiment 2) conditions, the sole exception being the ventral subiculum in Experiment 2. Although increased c-fos activation was found in both dorsal and ventral hippocampus, in Experiment 2 the relative increase was significantly greater in the dorsal hippocampus. Parahippocampal cortices responded heterogeneously: the perirhinal cortex failed to show increased activation in both experiments, in contrast to the entorhinal and postrhinal cortices. Subsequent comparisons confirmed that the perirhinal and postrhinal cortices responded in qualitatively different ways, the perirhinal cortex differing from the rest of the hippocampal formation. These experiments, which provide the first analysis of hippocampal Fos production during tests of allocentric spatial working memory, reveal that all components of the hippocampus are activated, but that under certain conditions the dorsal hippocampus is disproportionately involved