Diencephalic amnesia : rodent cognition, neural markers and electrophysiology.
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
The anterior thalamic nuclei (ATN), mammillary bodies and their interconnecting fibre tract the mammillothalamic tract (MTT) are important components of an extended hippocampal circuit for episodic memory. In humans, damage to the MTT or ATN from stroke, alcohol abuse, developmental brain injury and neurodegeneration is associated with severe anterograde amnesia. However, uncertainty regarding lesion boundaries and influence of pathology elsewhere in clinical settings limits firm conclusions regarding the specific contributions of the MTT and ATN to memory. These two structures are often considered to be functionally equivalent, but a direct comparison of ATN and MTT lesions in rats in Experiment 1 found that only ATN lesions impaired spatial reference memory and produced more severe deficits than MTT lesions on spatial working memory tasks in the radial-arm maze (RAM). ATN lesions also reduced zif268 expression to a greater degree in the retrosplenial cortex and hippocampal CA1 than MTT lesions. However, MTT and to a lesser extent, ATN lesions reduced NeuN cell counts in all three regions of the MB, so the relative impact of these lesions is not explained by MB pathology. Rather the greater ATN lesions deficits found here likely reflect disruption to additional processes associated with dense connections of the ATN with both hippocampal and cortical sites. In a previous study, an unexpected discrepancy between ATN and MB lesions was found on an object-place paired-associate task. This anomalous finding was examined and resolved in Experiment 2. Rats with MTT lesions had impaired acquisition of object-place associations in which probe tests revealed that they were likely to be responding on the basis of location, not direction or egocentric information. Experiment 3 provided highly novel evidence that MTT lesions can disrupt rhythmic oscillatory interactions at theta frequency (4-12Hz) between the ATN-PFC, ATN-HPC and HPC-PFC while rats make spatial memory choices in the RAM. It would therefore be expected that ATN lesions may even more profoundly impair oscillatory activity within the circuit. These findings provide critical insight into two different perspectives regarding the association between diencephalic pathology and amnesia. Specifically, it appears that other direct and indirect cortical and hippocampal inputs of the ATN make it a relatively more critical point of dysfunction than would be expected by a primary focus on the albeit important VTg, MB and MTT brainstem inputs to the extended memory system.