Inhibition of the ventral midline thalamus does not alter encoding, short-term holding or retrieval of spatial information in rats performing a water-escape working memory task.

Working memory (WM) is a function operating in three successive phases: encoding (sample trial), holding (delay), and retrieval (test trial) of information. Studies point to a possible implication of the thalamic reuniens nucleus (Re) in spatial WM (SWM). In which of the aforementioned 3 phases the Re has a function is largely unknown. Recently, in a delayed SWM water-escape task, we found that performance during the retrieval trial correlated positively with c-Fos expression in the Re nucleus, suggesting participation in retrieval. Here, we used the same task and muscimol (MUSC) inhibition or DREADD(hM4Di)-mediated inhibition of the Re during information encoding, right thereafter (thereby affecting the holding phase), or during the retrieval trial. A 6-hour delay separated encoding from retrieval. Concerning SWM, MUSC in the Re nucleus did not alter performance, be it during or after encoding, or during evaluation. CNO administered before encoding in DREADD-expressing rats was also ineffective, although CNO-induced inhibition disrupted set shifting performance, as found previously (Quet et al., Brain Struct Function 225, 2020), thereby validating DREADD efficiency. These findings are the first that do not support an implication of the Re nucleus in SWM. As most previous studies used T-maze alternation tasks, which carry high proactive interference risks, an important question to resolve now is whether the Re nucleus is required in (T-maze alternation) tasks using very short information-holding delays (seconds to minutes), and less so in other short-term spatial memory tasks with longer information holding intervals (hours) and therefore reduced interference risks.

Ventral midline thalamus activation is correlated with memory performance in a delayed spatial matching-to-sample task: A c-Fos imaging approach in the rat.

The reuniens (Re) and rhomboid (Rh) nuclei of the ventral midline thalamus are bi-directionally connected with the hippocampus and the medial prefrontal cortex. They participate in a variety of cognitive functions, including information holding for seconds to minutes in working memory tasks. What about longer delays? To address this question, we used a spatial working memory task in which rats had to reach a platform submerged in water. The platform location was changed every 2-trial session and rats had to use allothetic cues to find it. Control rats received training in a typical response-memory task. We interposed a 6 h interval between instruction (locate platform) and evaluation (return to platform) trials in both tasks. After the last session, rats were killed for c-Fos imaging. A home-cage group was used as additional control of baseline levels of c-Fos expression. C-Fos expression was increased to comparable levels in the Re (not Rh) of both spatial memory and response-memory rats as compared to their home cage counterparts. However, in spatial memory rats, not in their response-memory controls, task performance was correlated with c-Fos expression in the Re: the higher this expression, the better the performance. Furthermore, we noticed an activation of hippocampal region CA1 and of the anteroventral nucleus of the rostral thalamus. This activation was specific to spatial memory. The data point to a possible performance-determinant participation of the Re nucleus in the delayed engagement of spatial information encoded in a temporary memory.

The reuniens and rhomboid nuclei of the thalamus: A crossroads for cognition-relevant information processing?

Over the past twenty years, the reuniens and rhomboid (ReRh) nuclei, which constitute the ventral midline thalamus, have received constantly growing attention. Since our first review article about the functional contributions of ReRh nuclei (Cassel et al., 2013), numerous (>80) important papers have extended anatomical knowledge, including at a developmental level, introduced new and very original electrophysiological insights on ReRh functions, and brought novel results on cognitive and non-cognitive implications of the ReRh. The current review will cover these recent articles, more on Re than on Rh, and their contribution will be approached according to their affiliation with work before 2013. These neuroanatomical, electrophysiological or behavioral findings appear coherent and point to the ReRh nuclei as two major components of a multistructural system supporting numerous cognitive (and non-cognitive) functions. They gate the flow of information, perhaps especially from the medial prefrontal cortex to the hippocampus and back, and coordinate activity and processing across these two (and possibly other) brain regions of major cognitive relevance.