Lesions of the extended hippocampal system and activation of the anterior thalamus : from impairment to recovery.

Type of content
Theses / Dissertations
Publisher's DOI/URI
Thesis discipline
Psychology
Degree name
Doctor of Philosophy
Publisher
University of Canterbury
Journal Title
Journal ISSN
Volume Title
Language
English
Date
2020
Authors
Barnett, Sophie
Abstract

The mammillothalamic tract (MTT) and descending arm of the post-commissural fornix (PCFx) are key fibre tracts within an extended hippocampal system for episodic memory. Evidence from both clinical and animal model studies supports the involvement of the MTT in memory function. The role of the PCFx is less certain. Some MRI evidence suggests that the integrity of the PCFx is associated with memory in humans. However, PCFx transection in rats has produced negligible memory impairments. In rats, localised damage to the MTT, but not the PCFx, profoundly reduces the expression of immediate early gene proteins in distal structures in the extended hippocampal system. Experiment 1, however, found that both MTT and PCFx lesions equally impaired spatial working memory in the 12-arm radial arm maze (RAM). Both lesions also reduced Zif268 activity in the hippocampus (HPC) and retrosplenial cortex (RSC), albeit more extensively after MTT lesions. MTT and PCFx lesions also reduced spectral power and coherence across the ATN-HPC-prefrontal axis, although only MTT lesions attenuated HPC peak theta power. This evidence suggests that the descending PCFx has a more significant impact on memory than was anticipated by previous research in rats. This new evidence may lead to a revised account of the influence of subicular outputs from the hippocampal formation. Experiment 2 showed that the spatial working memory deficits produced by MTT lesions can be ameliorated through selective stimulation of glutamatergic neurons in the anterior thalamic nuclei (ATN). The ATN occupy a nodal position in the extended hippocampal system and are recipients of MTT efferents from the MB. Regular optogenetic theta burst stimulation (TBS) of the ATN led to a striking improvement in spatial working memory in rats with MTT lesions. This ATN stimulation also increased Zif268 expression in the RSC, HPC, prelimbic cortex and cingulate cortex and increased global spectral power and coherence within and across the ATN, HPC and PFC in the 2-14Hz frequency band. The lack of mnemonic effect found using closed-loop TBS, which was driven by each rat’s own hippocampal theta, suggests that the regularity of stimulation was critical for the recovery of memory function. This is the first study to show that long- lasting functional deficits after MTT lesions can be ameliorated. This latter evidence encourages developments to understand and treat clinical memory impairments in people with diencephalic brain injury.

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