Thalamocortical contributions to spatial working memory in the rat

Abstract

The human anterograde amnesic syndrome is a condition whereby the person can no longer learn new facts or pieces of information, and yet retains short-term memory processing, and older memories learnt before the onset of the syndrome. Both human case studies, and experimental animal models of this condition, have strongly indicated that damage to certain closely interrelated structures and cortical areas may be responsible for this failure to learn new information. Particular emphasis has been placed on the hippocampus, the mammillary bodies, certain thalamic nuclei, and those regions of cortex (particularly rhinal cortex and parts of prefrontal and cingulate cortices) that receive strong connections from the hippocampus and selective thalamic nuclei. While the evidence for the role of the hippocampus in mnemonic processing (especially regarding rats performing spatial tasks) is strong, the evidence is less certain concerning the involvement of the other structures and regions. This thesis has directly attempted to ascertain the relative contributions of certain thalamic nuclei, one region of cortex (the cingulate region), and a fibre pathway (the cingulum bundle) which connects the hippocampus and thalamus with cingulate cortex. The contribution of this fibre bundle received particularly close experimental scrutiny in this thesis as it's possible role in the neuroanatomical circuitry governing certain forms of mnemonic processing may have been underestimated. A series of five related experiments are described, each involving the DA pigmented strain of rat, whose spatial working memory processing was evaluated using a range of automated and maze-type tasks. These animals received a variety of lesions to the hippocampus, thalamus, cingulate cortex or the cingulum bundle, created by either neurotoxic or radiofrequency methods. Two forms of spatial memory processing were assessed; these consisted of egocentric and allocentric processing, and evidence is presented that they may be mediated by dissociable neuroanatomical circuits. Lesions of the mediodorsal thalamic nucleus and cingulate cortex had no effect on tasks assessing egocentric or allocentric processing. However, bilateral lesions of the cingulum bundle, whilst having no effect upon egocentric tasks, caused a severe impairment on tasks assessing allocentric processing. Lesions of the hippocampal system (the fornix) caused a severe impairment on both types of tasks. The nature of the putative neuroanatomical circuitry governing both allocentric and egocentric memory processing is discussed.