Conditioning- and time-dependent increases in context fear and generalization

Abstract

A prominent feature of fear memories and anxiety disorders is that they endure across extended periods of time. Here, we examine how the severity of the initial fear experience influences incubation, generalization, and sensitization of contextual fear memories across time. Adult rats were presented with either five, two, one, or zero shocks (1.2 mA, 2 sec) during contextual fear conditioning. Following a recent (1 d) or remote (28 d) retention interval all subjects were returned to the original training context to measure fear memory and/or to a novel context to measure the specificity of fear conditioning. Our results indicate rats that received two or five shocks show an "incubation"-like enhancement of fear between recent and remote retention intervals, while single-shocked animals show stable levels of context fear memory. Moreover, when fear was tested in a novel context, 1 and 2 shocked groups failed to freeze, whereas five shocked rats showed a time-dependent generalization of context memory. Stress enhancement of fear learning to a second round of conditioning was evident in all previously shocked animals. Based on these results, we conclude that the severity or number of foot shocks determines not only the level of fear memory, but also the time-dependent incubation of fear and its generalization across distinct contexts.

Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice

“…Control and PLX5622-treated mice were then subjected to either an aseptic tibial fracture with internal fixation or an anesthesia-matched sham procedure, after which they were assessed for markers of hippocampal and systemic inflammation, and for memory of an association learned preoperatively in a trace-fear conditioning (TFC) paradigm ( Figure 1C). TFC memory assessed in rodents within days following surgery correlates well with performance in a Morris water maze, a well-validated assay of learning and memory often used in clinical models of cognitive dysfunction (24,25).…”

Behavioral pattern separation and its link to the neural mechanisms of fear generalization

“…This time-dependent loss of details regarding threatening events may result in a decreased ability to discriminate between a novel, safe context and a stored threatening context, thereby making fear memories prone to generalize over time (Besnard and Sahay, 2015; Jasnow et al , 2016; Poulos et al , 2016). Furthermore, individuals with PTSD or excessive anxiety may rely more on familiarity than recollection when retrieving remote memories, contributing to enhanced threat uncertainty (Dolcos, 2013).…”

Persistent, generalized hypersensitivity of olfactory bulb interneurons after olfactory fear generalization

“…To promote fear generalization (Aizenberg & Geffen, 2013; Baldi, Lorenzini, & Bucherelli, 2004; Chen et al, 2011; Fanselow, 1980; Ghosh & Chattarji, 2015; Laxmi, Stork, & Pape, 2003; Poulos, Mehta, Lu, Amir, Livingston, Santarelli et al, 2016; Shaban, Humeau, Herry, Cassasus, Shigemoto, Ciocchi et al, 2006), paired training included 10 trials of an ~15-sec ester-odor (methyl valerate, MV) that approximately coterminated with a strong 1.2-mA, 0.5-sec footshock (Figure 1B–C). Shock-alone and odor-alone control training consisted of the same paradigm, but without the presentation of any odors (Figure 1B, middle) or any shocks (Figure 1B, bottom), respectively.…”