The nucleus reuniens: a key node in the neurocircuitry of stress and depression

Abstract

The hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC–hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression. Additionally, RE lesioning before CMS abrogates the well-known neuromorphological and endocrine correlates of CMS. In summary, this work highlights the importance of the reciprocal connectivity between the hippocampus and PFC in the establishment of stress-induced brain pathology and suggests a role for the RE in promoting resilience to depressive illness.

Astrocytic signaling supports hippocampal–prefrontal theta synchronization and cognitive function

“…Within this circuit, the dorsal hippocampus performs primarily cognitive functions, while the ventral relates to emotional behavior (Fanselow & Dong, 2010). Moreover, synchrony between oscillations of hippocampal dorsal or ventral subregions, and PFC has been related respectively to cognitive (O'Neill et al, 2013) and emotional behavior (Adhikari, Topiwala, & Gordon, 2010;Kafetzopoulos et al, 2017;Mateus-Pinheiro et al, 2016;Oliveira et al, 2013). Specifically, and despite the indirect connections, O'Neill and colleagues demonstrated that dHIP theta oscillations are synchronized with theta oscillations in the mPFC, and that theta synchrony is critical for a spatial memory task.…”

The nucleus reuniens of the thalamus sits at the nexus of a hippocampus and medial prefrontal cortex circuit enabling memory and behavior

“…On the one hand, lidocaine inactivation of RE resulted in a decreased coherence between 2-5 Hz delta oscillations in mPFC (PL) and HC, but had minimal effect on coupling at theta frequencies (Roy et al 2017). On the other hand, an N-methyl-D-aspartate (NMDA) lesion of RE impaired the coherence of mPFC-HC (PL-CA1) theta (and beta) frequency oscillations (Kafetzopoulos et al 2018). Interregional synchronization in the dorsal CA1-RE-mPFC direction was also observed.…”

“…Due, in part, to its key position in between the HC and mPFC, RE dysfunction may lead to major clinical problems, such as persistent working memory impairments and other types of cognitive dysfunction shared by many neuropsychiatric disorders (Meyer-Lindenberg et al 2001Lawrie et al 2002;Bassett et al 2012;Venkataraman et al 2012;Argyelan et al 2014). Although little is known about RE dysfunction, to date, RE has been suggested to be involved in Alzheimer's disease (Braak and Braak 1991;Moretti et al 2011;Hardenacke et al 2013), Korsakoff's syndrome (Visser et al 1999), autism (Ray et al 2005), stress and depression (Kafetzopoulos et al 2018), epilepsy (Hirayasu and Wada 1992;Bertram et al 2001;Graef et al 2009;Sloan and Bertram 2009;Wang et al 2009;Drexel et al 2011), and schizophrenia (Cohen et al 1998;Lambe et al 2007;Lisman et al 2010;Sigurdson et al 2010;Lisman 2012;Zhang et al 2012;Saalman 2014;Duan et al 2015). In Alzheimer's disease, there is a highly specific pattern of neurofibrillary tangles in RE, a pattern that was consistently restricted to those patients with the most severe symptoms (Braak and Braak 1991).…”

Respiration-coupled rhythms in prefrontal cortex: beyond if, to when, how, and why

“…It was shown recently (Kafetzopoulos et al 2017) in freely moving rats that nRE lesion reduced PFC–HC coherence without affecting PFC and HC LFP power, and had anti-depressive effects, as measured in the forced swim test and the chronic mild stress model of depressive behavior in rodents. It was thus proposed that reduced PFC–HC coherence was an important factor contributing to nRE’s impact on the overall brain connectome in chronic stress, along with other factors including stress-induced deficits of neuroplasticity, such as dendritic atrophy and spine loss in the PFC (Kafetzopoulos et al 2017). Regardless of mechanism, given the selective and task-dependent entrainment of PFC ensemble activity to RR, the simultaneous selective enhancement of RROs in HC by nRE may mediate task-dependent information flow from PFC to HC.…”