Post-training Inactivation of the Anterior Thalamic Nuclei Impairs Spatial Performance on the Radial Arm Maze

Abstract

The limbic thalamus, specifically the anterior thalamic nuclei (ATN), contains brain signals including that of head direction cells, which fire as a function of an animal's directional orientation in an environment. Recent work has suggested that this directional orientation information stemming from the ATN contributes to the generation of hippocampal and parahippocampal spatial representations, and may contribute to the establishment of unique spatial representations in radially oriented tasks such as the radial arm maze. While previous studies have shown that ATN lesions can impair spatial working memory performance in the radial maze, little work has been done to investigate spatial reference memory in a discrimination task variant. Further, while previous studies have shown that ATN lesions can impair performance in the radial maze, these studies produced the ATN lesions prior to training. It is therefore unclear whether the ATN lesions disrupted acquisition or retention of radial maze performance. Here, we tested the role of ATN signaling in a previously learned spatial discrimination task on a radial arm maze. Rats were first trained to asymptotic levels in a task in which two maze arms were consistently baited across training. After 24 h, animals received muscimol inactivation of the ATN before a 4 trial probe test. We report impairments in post-inactivation trials, suggesting that signals from the ATN modulate the use of a previously acquired spatial discrimination in the radial-arm maze. The results are discussed in relation to the thalamo-cortical limbic circuits involved in spatial information processing, with an emphasis on the head direction signal.

Progressive impairment of directional and spatially precise trajectories by TgF344-AD Rats in the Morris Water Task

“…This coincides with the reported early incidence of pathology in humans associated with the entorhinal cortex (Braak and Braak, 1995), but fails to address whether TgF344-AD pathology emerges in other limbic regions such as the anterior thalamic nuclei or retrosplenial cortex. This is particularly important given cell types coding for head direction are found in both regions (Clark and Taube, 2012; Taube, 2007), and damage to both regions can produce deficits in the directional accuracy of navigation (Clark and Harvey, 2016; Harvey et al, 2017; Vann et al, 2009). Whether TgF344-AD rats exhibit AD pathology and disrupted spatial signaling in limbic-thalamic and limbic-cortical regions at early stages of development is unknown and warrants investigation.…”

A new perspective on the head direction cell system and spatial behavior

“…cells (principally the anterior dorsal thalamus, but also the anterior ventral thalamus (Tsanov et al, 2011)) yield initial impairments in spatial learning on a T-maze and a Morris water maze that improve with training (Aggleton et al, 1996;Van Groen et al, 2002). No impairment was observed with anterior thalamic lesions on a radial arm maze task (Beracochea et al, 1989), though impairments in a reference memory version of this task have been observed following temporary inactivation of the region (Harvey et al, 2017). In mice, such inactivation of the anterior thalamic region is associated with indirect swim paths in the Morris water maze (Stackman et al, 2012).…”

Spatial memory deficits after vincristine-induced lesions to the dorsal hippocampus

“…This may explain why the speed of reference memory reacquisition seems not to be affected by the surgery in the present study, whereas lesioning induced a generally lower level of reference memory performance. Thus training prior to hippocampal lesions could have created spatial representations outside the hippocampus, such as in the anterior thalamic nuclei [53] or the hippocampal-diencephalic-cingulate network [54], which compensates for the loss caused by the dorsal hippocampal lesions. Importantly, the prefrontal cortex and the hippocampus have been reported to be involved in spatial working memory encoding, but they are not critical structures for the maintenance or retrieval of spatial cues [55].…”