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.

Keywords: head direction; hippocampus; limbic; navigation; spatial.

Figure 1

(A) Left: The anterodorsal thalamic nuclei (AD), anteroventral thalamic nuclei (AV), and stria medullaris (SM) are shown in a coronal view. Right: Representative coronal section depicting an infusion track through the ATN. Black arrowheads indicate track of infusion cannula. (B) The individual placements of infusion sites are indicated with black circles and presented against coronal views of the ATN at three rostral-caudal levels (in mm relative to bregma). Orange represents AD and gray represents AV.

Figure 2

Results of radial arm maze task acquisition. (A) Percentage of correct arm choices increased over trial blocks. (B,C) Spatial reference memory (RM) and spatial working memory (WM) errors decreased across trial blocks. (D) Latency to complete the task decreased across trial blocks. Mean ± SEM.

Figure 3

(A) Percentage of correct arm choices was higher in control animals than in muscimol animals. (B) Spatial reference memory (RM) error were significantly greater in muscimol animals than in control animals. (C) Spatial working memory-correct (WM-C) errors did not significantly differ between groups, but note that muscimol animals trended toward more WM-C errors compared to controls. (D) Spatial working memory-incorrect (WM-I) errors were significantly greater in muscimol animals than in control animals. (E) Latency to complete the task was significantly greater in muscimol animals than in control animals. (F) Muscimol and control animals made a similar total number of door exploration movements per trial. Mean + SEM.

Figure 4

Control and muscimol animals favored different search strategies during probe sessions. (A) Animals favored a mixed search strategy during the early trial blocks, but ultimately favored a spatial search strategy by the end of acquisition. (B) During probe trials, control animals favored a spatial search strategy while muscimol animals had no preferred search strategy. Mean + SEM.