An integrated analysis of the extended hippocampal system across species

The objective of this thesis was to investigate functional differences within the extended \nhippocampal system by 1. analysing its connectional topography and 2. looking at \nevidence for differential functions within its component structures. The main areas \nunder examination were A. the subiculum and B. its diencephalic targets, along with C. \nthe fornix, the principle white matter tract connecting these structures. \n \nRetrograde tracer experiments in rodents and primates revealed consistent topographies \nin the subiculum projections to these diencephalic target sites, with distinctions \noccurring primarily along the proximal-distal and laminar subicular axes in rodents and \nprimarily along the anterior-posterior and laminar subicular axes in primates. Based on \ndifferent input patterns to the proximal subiculum (principally from sites processing \nobject information) and distal subiculum (principally from sites processing \nspatial/context information) it was predicted that this proximal-distal axis would show \nfunctional activation differences in rodents for matched object:spatial tasks. Immediate \nearly gene imaging (using zif268 expression) did not, however, reveal clear-cut gradient \ndifferences, although there were indications of the expected bias to object memory in \nthe proximal subiculum. \n \nDiffusion MRI was used to study the fornix by separating its precommissural and \npostcommissural connections in a healthy older and cognitively impaired human \npopulation. Reliable topographic differences were found for the precommissural and \npostcommissural fornix in each group but cognitive function proved difficult to \ndifferentiate between the tracts for the tasks used. Lastly, fornix reconstructions were \nalso found to be separable according to their links with either the anterior or posterior \n \n \n \nhippocampus in a healthy population. These distinctions provide another way of \nstudying the fornix in terms of relating different functional properties with different sets \nof hippocampal connections. It is assumed that different populations of fornical fibres \nshould underlie different aspects of memory/ cognitive tasks involving the fornix, \nmaking their segregation informative in future studies researching this tract. detailing \nthe nature of the connections within the extended hippocampal system, this thesis lays \nthe groundwork for future studies investigating the relative roles of its component \nstructures in cognitive function