Inactivation of the Anterior Cingulate Reveals Enhanced Reliance on Cortical Networks for Remote Spatial Memory Retrieval after Sequential Memory Processing

Abstract

One system consolidation model suggests that as time passes, ensembles of cortical neurons form strong connections to represent remote memories. In this model, the anterior cingulate cortex (ACC) serves as a cortical region that represents remote memories. However, there is debate as to whether remote spatial memories go through this systems consolidation process and come to rely on the ACC. The present experiment examined whether increasing the processing demand on the hippocampus, by sequential training on two spatial tasks, would more fully engage the ACC during retrieval of a remote spatial memory. In this scenario, inactivation of the ACC at a remote time point was hypothesized to produce a severe memory deficit if rats had been trained on two, sequential spatial tasks. Rats were trained on a water maze (WM) task only or a WM task followed by a radial arm maze task. A WM probe test was given recently or remotely to all rats. Prior to the probe test, rats received an injection of saline or muscimol into the ACC. A subtle deficit in probe performance was found at the remote time point in the group trained on only one spatial task and treated with muscimol. In the group trained on two spatial tasks and treated with muscimol, a subtle deficit in probe performance was noted at the recent time point and a substantial deficit in probe performance was observed at the remote time point. c-Fos labeling in the hippocampus revealed more labeling in the CA1 region in all remotely tested groups than recently tested groups. Findings suggest that spatial remote memories come to rely more fully on the ACC when hippocampal processing requirements are increased. Results also suggest continued involvement of the hippocampus in spatial memory retrieval along with a progressive strengthening of cortical connections as time progresses.

The Acquisition and Expression of Remote Spatial Memories Formed During the Juvenile Period are Impaired by AMPAr Blockade

“…Inactivation of the ACC has been shown to impair performance on remote memory tests (Wartman et al, 2014). These findings indicate the existence of a hippocampal-cortical network that becomes active during remote spatial memory testing and therefore, contributes to the memory retrieval process (Clark et al, 2007;Teixeira et al, 2006;Wartman et al, 2014).…”

“…Increased activity and structural changes have been observed in the ACC during remote memory tests, indicative of remote memory storage (Goshen et al, 2011;Wartman et al, 2014). Inactivation of the ACC has been shown to impair performance on remote memory tests (Wartman et al, 2014). These findings indicate the existence of a hippocampal-cortical network that becomes active during remote spatial memory testing and therefore, contributes to the memory retrieval process (Clark et al, 2007;Teixeira et al, 2006;Wartman et al, 2014).…”

“…Conversely, the metabolic activity in other cortical areas, specifically the anterior cingulate cortex, increased during recollection of those memories, suggesting that the long-term storage lies in that area of the brain (Bontempi et al, 1999). Damage to the cingulate cortex has also proven to impede the retention of long-term remote memories, further demonstrating the role of the cingulate cortex in the long-term memory storage process (Insel & Takehara-Nishiuchi, 2013;Wartman et al, 2014).…”

“…Memory consolidation involves two levels of processing: the cellular level, which involves regulating gene expression and protein synthesis in localized circuits through intracellular signaling cascades, and the brain systems level, which involves more gradual changes in brain structures spanning over a much longer time frame (Einarsson & Nader, 2012;Wartman et al, 2014). The long-term memory consolidation process is mediated by various intricate and complex neural connections between the cingulate cortex, the entorhinal cortices, and the hippocampus (Insel & Takehara-Nishiuchi, 2013).…”

“…An elevation in c-Fos expression has been shown to occur in the hippocampus during retrieval of remote memory in animals after being trained on the water maze (Wartman et al, 2014). Increased activity and structural changes have been observed in the ACC during remote memory tests, indicative of remote memory storage (Goshen et al, 2011;Wartman et al, 2014). Inactivation of the ACC has been shown to impair performance on remote memory tests (Wartman et al, 2014).…”