Nucleus Reuniens Is Required for Encoding and Retrieving Precise, Hippocampal-Dependent Contextual Fear Memories in Rats

Abstract

The nucleus reuniens (RE) is a ventral midline thalamic nucleus that interconnects the medial prefrontal cortex (mPFC) and hippocampus (HPC). Considerable data indicate that HPC-mPFC circuits are involved in contextual and spatial memory; however, it is not clear whether the RE mediates the acquisition or retrieval of these memories. To examine this question, we inactivated the RE with muscimol before either the acquisition or retrieval of pavlovian fear conditioning in rats; freezing served as the index of fear. We found that RE inactivation before conditioning impaired the acquisition of contextual freezing, whereas inactivation of the RE before retrieval testing increased the generalization of freezing to a novel context; inactivation of the RE did not affect either the acquisition or expression of auditory fear conditioning. Interestingly, contextual conditioning impairments were absent when retrieval testing was also conducted after RE inactivation. Contextual memories acquired under RE inactivation were hippocampal independent, insofar as contextual freezing in rats conditioned under RE inactivation was insensitive to intrahippocampal infusions of the NMDA receptor antagonist aminophosphonovalerate. Together, these data reveal that the RE supports hippocampal-dependent encoding of precise contextual memories that allow discrimination of dangerous contexts from safe contexts. When the RE is inactive, however, alternate neural systems acquire an impoverished contextual memory that is expressed only when the RE is off-line.

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

“…That is, in contrast to temporal context memory, working memory helps reject nearby items but does this less well for distal items (the opposite pattern). The mPFC → RE silencing effect on working memory retrieval during memory for sequences of events is gener-ally consistent with the role of RE in SWM tasks (e.g., Hembrook et al 2012;Cassel et al 2013;Hallock et al 2013b;Griffin 2015;Viena et al 2018), and, from a retrieval standpoint, similar to the role of RE in hippocampal-dependent contextual fear memory (Ramanathan et al 2018). Though more work needs to be done to test the role of RE in a variety of temporal tasks, these early findings suggest that the cognitive role of RE is not restricted to processing spatial variables, but rather RE influences multiple memory functions that likely contribute to episodic memory.…”

Functional Organisation and Connectivity of the Dorsal Column Nuclei Complex Reveals a Sensorimotor Integration and Distribution Hub

“…It is not clear whether the Cu projections terminate directly onto cells that project to the Re, but their colocalization may indicate a pathway for information from the DCN to access the limbic system. The Re interactions with the hippocampus form a reciprocal network with the medial prefrontal cortex and contribute to spatial working memory (Griffin, 2015) and contextual memories for discriminating dangerous and safe contexts (Ramanathan, Ressler, Jin, & Maren, 2018). The Cu-Re connection might convey somatosensory information to this network, which is used for spatial working memory.…”

Single prolonged stress alters neural activation in the periacqueductal gray and midline thalamic nuclei during emotional learning and memory

“…The Rh and Re, due to its interconnectivity with both the mPFC and hippocampus, is critical for spatial working memory (Hallock et al 2016) as well as contextual fear memory (Ramanathan et al 2018). Extinction memory recall is heavily dependent on contextual feature processing during extinction training and testing (Bouton et al 2006;Maren et al 2013).…”

“…The rhomboid (Rh) nucleus shows increased c-Fos expression following fear extinction (Furlong et al 2016). The Rh and the ventrally adjacent nucleus reunions (RE) are important for facilitating functional connectivity between the mPFC and hippocampus (Hallock et al 2016;Maisson et al 2018) and is specifically critical for retrieval of specific contextual information during fear conditioning (Ramanathan et al 2018). The medial habenula (mHab) has been implicated in the regulation of fear behavior (Zhang et al 2016).…”