Basal forebrain cholinergic systems as circuits through which traumatic stress disrupts emotional memory regulation

Abstract

Contextual and spatial systems facilitate changes in emotional memory regulation brought on by traumatic stress. Cholinergic basal forebrain (chBF) neurons provide input to contextual/spatial systems and although chBF neurons are important for emotional memory, it is unknown how they contribute to the traumatic stress effects on emotional memory. Clusters of chBF neurons that project to the prefrontal cortex (PFC) modulate fear conditioned suppression and passive avoidance, while clusters of chBF neurons that project to the hippocampus (Hipp) and PFC (i.e. cholinergic medial septum and diagonal bands of Broca (chMS/DBB neurons) are critical for fear extinction. Interestingly, neither Hipp nor PFC projecting chMS/DBB neurons are critical for fear extinction. The retrosplenial cortex (RSC) is a contextual/spatial memory system that receives input from chMS/DBB neurons, but whether this chMS/DBB-RSC circuit facilitates traumatic stress effects on emotional memory remain unexplored. Traumatic stress leads to neuroinflammation and the buildup of reactive oxygen species. These two molecular processes may converge to disrupt chBF circuits enhancing the impact of traumatic stress on emotional memory.

Keywords: Cholinergic; Contextual conditioning; Extinction; Fear conditioning; Inflammation; Medial septum; Occasion-setting; Oxidative species.

Figure 1.

Effects of SPS on c-Fos levels in the RSC (granular and agranular regions) at baseline, fear conditioning, extinction training, and extinction testing. A) representative near-infrared immunohistochemical image staining for c-Fos in the RSC. B) Effects of SPS on c-Fos levels during baseline and behavioral tasks. Baseline c-Fos levels in the RSC was lower in SPS rats when compared to controls and this effect approached significance. For the CS-Fear treatment c-Fos levels were lower during fear conditioning alone and this potential interaction (stress x treatment) approached significance. For the CS-Only treatment there were no stress effects.