Transient inactivation of the thalamic nucleus reuniens and rhomboid nucleus produces deficits of a working-memory dependent tactile-visual conditional discrimination task.

Abstract

Working memory depends on communication between the hippocampus and the prefrontal cortex (PFC); however, the neural circuitry that mediates interactions between these brain areas has not been well characterized. Two candidate structures are the thalamic reuniens (RE) and rhomboid (Rh) nuclei, which are reciprocally connected with both the hippocampus and PFC. These known anatomical connections suggest that RE/Rh may be involved in mediating hippocampal-prefrontal communication, and therefore may be critical for working memory processing. To test the hypothesis that RE/Rh are necessary for working memory, we trained separate groups of rats to perform one of two tasks in a T-maze. The first task was a working memory-dependent conditional discrimination (CDWM) task, and the second task was a non-working memory-dependent conditional discrimination (CD) task. These tasks took place in the same maze, featured the same number of trials, and utilized the same cue (a tactile-visual maze insert). After rats had learned either task, RE/Rh were transiently inactivated with the GABAA receptor agonist muscimol, and performance was assessed. RE/Rh inactivation caused performance deficits on the CDWM task, but not the CD task. This result suggests that RE/Rh are a necessary component of working memory task performance, which is also thought to depend on the hippocampal-prefrontal circuit. RE/Rh inactivation did not cause a performance deficit on the CD task, suggesting that RE/Rh have dissociable contributions to working memory-dependent and non-working memory-dependent tasks, independently of the known contributions of these two thalamic nuclei to the sensorimotor and attention-related aspects of other memory tasks.

Transient inactivation of the medial prefrontal cortex impairs performance on a working memory-dependent conditional discrimination task.

“…Our lab previously reported that inactivation of the nucleus reuniens/rhomboid nucleus (Re/Rh) impaired performance on the CD WM task, without impacting performance on the working-memory-independent CD STANDARD task (Hallock et al, 2013b). These midline thalamic nuclei are bidirectionally connected to both the hippocampus and mPFC (Cavdar et al, 2008; Vertes, 2002; Vertes, Hoover, Szigeti-Buck, & Leranth, 2007).…”

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

“…Based on these patterns of connections, several recent behavioral studies have examined the role of RE (and the dorsally adjacent rhomboid nucleus, RH) in various spatial working memory tasks (Hembrook and Mair, 2011; Hembrook et al, 2012; Loureiro et al, 2012; Cholvin et al, 2013; Hallock et al, 2013; Layfield et al, 2015). The general conclusion from these studies is that RE/RH is most directly involved in those tasks that involve the cooperative actions of the mPFC and the hippocampus (for review, Cassel et al, 2013; Vertes et al 2015; Griffin, 2015).…”

Interaction of nucleus reuniens and entorhinal cortex projections in hippocampal field CA1 of the rat

“…A growing number of behavioural studies has provided evidence that RE is indeed involved in cognitive functions, most likely by coordinating neuronal activities in hippocampus and mPFC (Dolleman-van der Weel et al, 2009;Davoodi et al 2011;Eleore et al 2011;Hembrook et al 2011;Loureiro et al 2012;Prasad et al 2012;Cholvin et al 2013;Hallock et al 2013;Xu and Sűdhof 2013;Saalmann 2014;Bobal and Savage 2015;Ito et al 2015;Layfield et al 2015;Prasad et al 2016). Because mPFC lacks a direct return projection to the hippocampus (Sesack et al 1989;Jay and Witter 1991), RE might relay mPFC-processed information back to the hippocampus as part of a closed CA1-mPFC-RE-CA1 circuit Xu and Sűdhof 2013).…”

“…Recent studies have indicated the importance of RE for cognitive processes, such as behavioural flexibility, strategy shifting, inhibitory response control, associative learning, memory consolidation, working memory, fear memory, memory generalization, goal-directed navigation, and executive behaviours (Dollemanvan der Weel et al 2009;Davoodi et al 2011;Eleore et al 2011;Hembrook et al 2011;Kincheski et al 2012;Loureiro et al 2012;Cholvin et al 2013;Hallock et al 2013;Prasad et al 2013;Varela et al 2013;Wheeler et al 2013;Xu and Sűdhof 2013;Duan et al 2015;Griffin 2015;Ito et al 2015;Layfield et al 2015;Anderson et al 2015;Prasad et al 2016). This variety of memory-related behaviours has also been associated with the interplay between the medial prefrontal cortex (mPFC) and the hippocampus (Jin and Maren 2015).…”