Lesions of the ventral midline thalamus produce deficits in reversal learning and attention on an odor texture set shifting task

Abstract

The nucleus reuniens (RE) of the ventral midline thalamus in strongly reciprocally connected with the hippocampus (HF) and the medial prefrontal cortex (mPFC) and has been shown to mediate the transfer of information between these structures. It has become increasingly well established that RE serves a critical role in mnemonic tasks requiring the interaction of the HF and mPFC, but not tasks relying solely on the HF. Very few studies have addressed the independent actions of RE on prefrontal executive functioning. The present report examined the effects of lesions of the ventral midline thalamus, including RE and the dorsally adjacent rhomboid nucleus (RH) in rats on attention and behavioral flexibility using the attentional set shifting task (AST). The task uses odor and tactile stimuli to test for attentional set formation, attentional set shifting, behavioral flexibility and reversal learning. By comparison with sham controls, lesioned rats were significantly impaired on reversal learning and intradimensional (ID) set shifting. Specifically, RE/RH lesioned rats were impaired on the first reversal stage of the task which required a change in response strategy to select a previously non-rewarded stimulus for reward. RE/RH lesioned rats also exhibited deficits in the ability to transfer or generalize rules of the task which consists of making the same modality-based choices (e.g., odor vs. tactile) to different sets of stimuli in the ID stage of the task. These results demonstrate that in addition to its role in tasks dependent on HF-mPFC interactions, RE/RH is also critically involved cognitive/executive functions associated with the medial prefrontal cortex. As such, the deficits in the AST task produced by RE/RH lesions suggest the ventral midline thalamus directly contributes to flexible goal directed behavior.

Prefrontal projections to the thalamic nucleus reuniens mediate fear extinction

“…The fact that the RE is critically involved in extinction learning and recall is in line with previous work demonstrating the importance of the midline thalamus in both memory and emotion 23 – 25 , 32 – 35 . Importantly, a recent study demonstrated that the RE is important for maintaining the specificity of contextual fear memory 25 .…”

Inactivation of nucleus reuniens impairs spatial working memory and behavioral flexibility in the rat

“…In essence, RE inactivation not only altered working memory and spatial perseveration but may have disrupted learned response strategies. In like fashion, we recently found that RE lesions not only altered behavioral flexibility but impaired rule abstraction, or the ability to use previously learned rule/response strategies to guide responses to new sensory stimuli (Linley et al, ).…”

“…Premature responding is viewed as a failure of impulse control and is seen with lesions of the infralimbic cortex on the 5‐CSRTT task (Chudasama et al, 2003). Finally, we recently described deficits in attention and reversal learning (a measure of behavioral flexibility) on an attentional set shifting task in RE lesioned rats (Linley et al, ).…”

ACC Theta Improves Hippocampal Contextual Processing during Remote Recall

“…Interestingly, such spatial working memory tasks are dependent upon both the HC and ACC (Floresco et al, 1997;Izaki et al, 2000;Lee and Kesner, 2003;Churchwell et al, 2010), suggesting that RE-based interactions are integral to proper working memory function. Additionally, RE inactivation also impairs behavioral flexibility leading to perseveration in win-shift tasks (Viena et al, 2018) and an inability to generalize response strategies between contexts (Linley et al, 2016), which indicates a broader role in cognition for RE-based interactions. Although the current study involved a completely different task, it is conceivable that these same connections could mediate interactions in the opposite direction during remote recall.…”