Title

Anatomical organization of entorhinal-hippocampal projections

Date of Completion

January 2007

Keywords

Biology, Neuroscience

Degree

Ph.D.

Abstract

The entorhinal cortex (EC) is a core component of the medial temporal lobe memory system. Understanding the macro and micro-circuitry of the EC and its connectivity within the forebrain may shed light on memory function and dysfunction. Here we use an animal model (the rat) to investigate the organization of intrinsic and extrinsic projections in the entorhino-hippocampal circuit. ^ The overarching hypothesis of this thesis is that anatomically distinct circuits within the EC and its efferents constrain information processing in the hippocampus. Cortical and sub-cortical afferents terminate in limited mediolateral portions of the EC that correspond with cytoarchitectonic divisions. The extent to which unique information conveyed by these inputs is integrated within EC associational networks and the degree to which this integrated information is conveyed to the hippocampus is presently ill defined. ^ Here we examine the organization of intrinsic projections within the EC using antero- and retrograde tracing techniques. We extend previous findings that entorhinal intrinsic projections are organized into three bands (outer, intermediate, inner), which transcend cytoarchitectonic and cortico-cortically defined subdivisions. Further, we explore thalamic projections to the EC bands and downstream targets in the hippocampus. Following EC retrograde tracer injections we conclude that nucleus reuniens afferents respect band boundaries and follow a dorsolateral-to-outer and ventromedial-to-inner band topography. Following retrograde tracer injections along the septotemporal axis of CA1 we confirm that the reuniens-to-CA1 projection follows a dorsal-to-septal and ventral-to-temporal topography. Thus, the origins of thalamo-hippocampal and thalamo-entorhinal projections are in accord. Finally, we examine the degree of convergence/divergence in the entorhinal projection to CA1. Following injections of anterograde tracer within the EC as well as retrograde tracer injections along the septotemporal axis of CA1 we conclude that the EC III-to-CA1 projection is organized in a tripartite manner such that the outer band projects to the septal 50% while the intermediate and inner bands project to the mid-septotemporal and temporal quartiles of CA1 respectively. ^ Thus, our findings strongly support the hypothesis that associational networks that are the EC bands function to integrate (within band) and segregate (between bands) information and this organization is maintained in the EC-to-CA1 projection. ^