Abstract
Damage to the mammillothalamic tract (MTT) produces memory impairments in both humans and rats, yet it is still not clear why this diencephalic pathway is vital for memory. One suggestion is that it is an important route for midbrain inputs to reach a wider cortical and subcortical network that supports memory. Consistent with this idea, MTT lesions produce widespread hypoactivity in distal brain regions as measured by the immediate-early gene, c-fos. To determine whether these findings were selective to c-fos or reflected more general changes in neuronal function, we assessed the effects of MTT lesions on the expression of the immediate-early gene protein, Zif268 and the metabolic marker, cytochrome oxidase, in the retrosplenial cortex and hippocampus. The lesions decreased levels of both activity markers in the superficial and deep layers of the retrosplenial cortex in both its granular and dysgranular subregions. In contrast, no significant changes were observed in the hippocampus, despite the MTT-lesioned animals showing marked impairments on T-maze alternation. These findings are consistent with MTT lesions providing important, indirect inputs for normal retrosplenial cortex functioning. These distal functional changes may contribute to the memory impairments observed after MTT lesions.
Highlights
The mammillothalamic tract (MTT) is a white matter bundle, which carries unidirectional projections from the mammillary bodies to the anterior thalamic nuclei
This account is consistent with previous findings, as lesions to the MTT or the anterior thalamic nuclei reduce the expression of the immediate early gene c-fos in both the retrosplenial cortex and the dorsal hippocampus (Jenkins et al, 2002a,b; Jenkins et al, 2004; Poirier and Aggleton, 2009; Vann and Albasser, 2009; Vann, 2013; but see Dupire et al, 2013, Loukavenko et al, 2015)
The present study investigated whether the MTT lesion-induced changes in the hippocampus and retrosplenial cortex are selective to the immediate-early gene c-fos, or reflect a more widespread dysfunction
Summary
The mammillothalamic tract (MTT) is a white matter bundle, which carries unidirectional projections from the mammillary bodies to the anterior thalamic nuclei. One possibility is that disconnecting the mammillary body projections to the anterior thalamic nuclei results in a loss of ascending midbrain inputs, e.g., from Gudden’s tegmental nuclei (e.g., Vann, 2013; Vann and Nelson, 2015), which in turn causes distal hypoactivity in other connected memory structures This account is consistent with previous findings, as lesions to the MTT or the anterior thalamic nuclei reduce the expression of the immediate early gene c-fos in both the retrosplenial cortex and the dorsal hippocampus (Jenkins et al, 2002a,b; Jenkins et al, 2004; Poirier and Aggleton, 2009; Vann and Albasser, 2009; Vann, 2013; but see Dupire et al, 2013, Loukavenko et al, 2015). The lesions in the second cohort were verified both behaviorally and immunohistochemically, i.e., rats were tested on a reinforced T-maze alternation task and the tissue was processed for calbindin-staining to visualize the dense fibrous stain in the ventrolateral part of the anteroventral thalamic nucleus attributed to mammillothalamic input (e.g., Rogers and Resibois, 1992)
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