Retrosplenial Cortex Effects Contextual Fear Formation Relying on Dysgranular Constituent in Rats

Abstract

Animal contextual fear conditioning (CFC) models are the most-studied forms used to explore the neural substances of posttraumatic stress disorder (PTSD). In addition to the well-recognized hippocampal–amygdalar system, the retrosplenial cortex (RSC) is getting more and more attention due to substantial involvement in CFC, but with a poor understanding of the specific roles of its two major constituents—dysgranular (RSCd) and granular (RSCg). The current study sought to identify their roles and underlying brain network mechanisms during the encoding processing of the rat CFC model. Rats with pharmacologically inactivated RSCd, RSCg, and corresponding controls underwent contextual fear conditioning. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning was performed for each animal. The 5-h and 24-h retrieval were followed to test the formation of contextual memory. Graph theoretic tools were used to identify the brain metabolic network involved in encoding phase, and changes of nodal (brain region) properties linked, respectively, to disturbed RSCd and RSCg were analyzed. Impaired retrieval occurred in disturbed RSCd animals, not in RSCg ones. The RSC, hippocampus (Hip), amygdala (Amy), piriform cortex (Pir), and visual cortex (VC) are hub nodes of the brain-wide network for contextual fear memory encoding in rats. Nodal degree and efficiency of hippocampus and its connectivity with amygdala, Pir, and VC were decreased in rats with disturbed RSCd, while not in those with suppressed RSCg. The RSC plays its role in contextual fear memory encoding mainly relying on its RSCd part, whose condition would influence the activity of the hippocampal–amygdalar system.

Disrupting direct inputs from the dorsal subiculum to the granular retrosplenial cortex impairs flexible spatial memory in the rat

“…Findings from a very different type of behavioural task, contextual fear conditioning, also implicate both the hippocampus (including the dorsal subiculum) and retrosplenial cortex in learning about space (Anagnostaras et al, 2001; Keene & Bucci, 2008; de Melo et al, 2020; Miller et al, 2014; Pan et al, 2022; Smith et al, 2012). Meanwhile, immediate‐early gene analyses indicate that the two regions have complementary roles in spatial tasks (Czajkowski et al, 2020; Frankland & Bontempi, 2005).…”

Medial amygdalar tau is associated with anxiety symptoms in preclinical Alzheimer’s disease

“…This shift might relate to early neuropsychiatric symptoms: lower connectivity from medial amygdala to the retrosplenial cluster correlated with higher reported symptoms of anxiety in the A4 cohort. Of all the nodes of the posterior DMN, retrosplenial cortex is perhaps the region with the closest relationship to anxiety: amygdala and RSC play complementary roles in fear extinction (81); the RSC plays a role in fear memory retrieval, and with the amygdala, memory for acute trauma (82,83); and decreased connectivity between the mesial temporal lobe (including the amygdala specifically) and RSC has been implicated in context-dependent fear conditioning in animal studies (84)(85)(86). We also observed a positive association between lateral group tau binding and anxiety in the amyloid-positive group, as well as an interaction between amyloid status and mood symptoms in all three amygdalar divisions.…”

Disrupting direct inputs from the dorsal subiculum to the granular retrosplenial cortex impairs spatial memory in the rat

“…Findings from a very different type of behavioural task, contextual fear conditioning, also implicate both the hippocampus (including the dorsal subiculum) and retrosplenial cortex in learning about space (Anagnostaras et al, 2001;Keene & Bucci, 2008;Melo et al, 2020;Miller et al, 2014;Pan et al, 2022;Smith et al, 2012). Meanwhile, immediate-early gene analyses indicate that the two regions have complementary roles in spatial tasks (Czajkowski et al, 2020;Frankland & Bontempi, 2005).…”