Abstract
Contextual fear conditioning is a Pavlovian conditioning paradigm capable of rapidly creating fear memories to contexts, such as rooms or chambers. Contextual fear conditioning protocols have long been utilized to evaluate how fear memories are consolidated, maintained, expressed, recalled, and extinguished within the brain. These studies have identified the lateral portion of the amygdala and the dorsal portion of the hippocampus as essential for contextual fear memory consolidation. The current study was designed to evaluate how two different contextual fear memories alter amygdala and hippocampus microglia, brain derived neurotrophic factor (BDNF), and phosphorylated cyclic-AMP response element binding (pCREB). We find rats provided with standard contextual fear conditioning to have more microglia and more cells expressing BDNF in the dentate gyrus as compared to a context only control group. Additionally, standard contextual fear conditioning altered microglia morphology to become amoeboid in shape – a common response to central nervous system insult, such as traumatic brain injury, infection, ischemia, and more. The unpaired fear conditioning procedure (whereby non-reinforced and non-overlapping auditory tones were provided at random intervals during conditioning), despite producing equivalent levels of fear as the standard procedure, did not alter microglia, BDNF or pCREB number in any dorsal hippocampus or lateral amygdala brain regions. Despite this, the unpaired fear conditioning protocol produced some alterations in microglia morphology, but less compared to rats provided with standard contextual fear conditioning. Results from this study demonstrate that contextual fear conditioning is capable of producing large alterations to dentate gyrus plasticity and microglia, whereas unpaired fear conditioning only produces minor changes to microglia morphology. These data show, for the first time, that Pavlovian fear conditioning protocols can induce similar responses as trauma, infection or other insults within the central nervous system.
Highlights
We find that microglia number and brain derived neurotrophic factor (BDNF) expression increase in the dentate gyrus (DG) subregions of the dorsal hippocampus (DH), following Contextual fear conditioning (CFC), as compared to a context only (CO) control group
BDNF Expression in DG Is Increased by CFC Following quantification of neurons expressing phosphorylated cyclic-AMP response element binding (pCREB), the number of cells expressing BDNF was quantified in lateral amygdala (LA) and DH, and compared between groups
Contrary to pCREB data above, one-way analyses of variances (ANOVAs) revealed a significant difference in BDNF expression as a function of condition in DH subregion DG [F(2,55) = 8.1509, p < 0.001]
Summary
Contextual fear conditioning (CFC) is a Pavlovian conditioning protocol whereby an animal, typically a rodent, is placed into a context (conditioned stimulus; CS) and provided with noxious stimuli (unconditioned stimulus; US) (Foa et al, 1992; Rothbaum and Davis, 2003; Fanselow, 2010; LeDoux, 2014; Chaaya et al, 2018). CFC, along with similar fear conditioning protocols are utilized to replicate the behavioral events that lead to the development of fear-based disorders, namely, post-traumatic stress disorder (PTSD) (Foa et al, 1992; Rothbaum and Davis, 2003; Fanselow, 2010; Maren, 2011; LeDoux, 2014; Chaaya et al, 2018).
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