Fear generalization is one of the main symptoms of posttraumatic stress disorder. In rodents, the anterior cingulate cortex (ACC) and the hippocampus (HPC) control the expression of contextual fear memory generalization. Consistently, ACC projections to the ventral HPC contribute to contextual fear generalization. However, the roles of ACC…

Fear is an adaptive emotion that serves to protect an organism against potential dangers. It is often studied using classical conditioning paradigms where a conditioned stimulus is paired with an aversive unconditioned stimulus to induce a threat response. Less commonly studied is a phenomenon that is related to this form of conditioning, known as…

NMDA receptors (NMDARs) and AMPA receptors (AMPARs) in amygdala nuclei and the dorsal hippocampus (dHipp) are critical for fear conditioning. Enhancements in synaptic AMPAR expression in amygdala nuclei and the dHipp are critical for fear conditioning, with some studies observing changes in AMPAR expression across many neurons in these brain…

There are sex differences in anxiety disorders with regard to occurrence and severity of episodes such that females tend to experience more frequent and more severe episodes. Contextual fear learning and generalization are especially relevant to anxiety disorders, which are often defined by expressing fear and/or anxiety in safe contexts. In…

Recent data reveal that the thalamic nucleus reuniens (RE) has a critical role in the extinction of conditioned fear. Muscimol (MUS) infusions into the RE impair within-session extinction of conditioned freezing and result in poor long-term extinction memories in rats. Although this suggests that RE inactivation impairs extinction learning, it is…

Inclusion of male and female subjects in behavioral neuroscience research requires a concerted effort to characterize sex differences in standardized behavioral assays. Sex differences in hippocampus-dependent assays have been widely reported but are still poorly characterized. In the present study, we conducted a parametric analysis of…

Dopamine participates in encoding memories and could either encode rewarding/aversive value of unconditioned stimuli or act as a novelty signal triggering contextual learning. Here we show that intraperitoneal injection of the dopamine D1/5R antagonist SCH23390 impairs contextual fear conditioning and tone-shock association, while intrahippocampal…

Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage in a variety of both conditioned and unconditioned responses, the last several decades have seen the field narrow its focus to measure freezing as the sole indicator of conditioned fear.…

Fear-motivated avoidance extinction memory is prone to hippocampal brain-derived neurotrophic factor (BDNF)-dependent reconsolidation upon recall. Here, we show that extinction memory recall activates mammalian target of rapamycin (mTOR) in dorsal CA1, and that post-recall inhibition of this kinase hinders avoidance extinction memory persistence…

Early life stress (ELS) experiences can cause changes in cognitive and affective functioning. This study examined the persistent effects of a single traumatic event in infancy on several adult behavioral outcomes in male and female C57BL/6J mice. Mice received 15 footshocks in infancy and were tested for stress-enhanced fear learning, extinction…

Temporal association learning (TAL) allows for the linkage of distinct, nonsynchronous events across a period of time. This function is driven by neural interactions in the entorhinal cortical-hippocampal network, especially the neural input from the pyramidal cells in layer III of medial entorhinal cortex (MECIII) to hippocampal CA1 is crucial…

In an ever-changing environment, survival depends on learning which stimuli represent threat, and also on updating such associations when circumstances shift. It has been claimed that humans can acquire physiological responses to threat-associated stimuli even when they are unaware of them, but the role of awareness in updating threat…

An adaptive memory system should prioritize information surrounding a powerful learning event that may prove useful for predicting future meaningful events. The behavioral tagging hypothesis provides a mechanistic framework to interpret how weak experiences persist as durable memories through temporal association with a strong experience. Memories…

Strong evidence supports a role for protein degradation in fear memory formation. However, these data have been largely done in only male animals. Here, we found that following contextual fear conditioning, females, but not males, had increased levels of proteasome activity and K48 polyubiquitin protein targeting in the dorsal hippocampus, the…

The ability to generate memories that persist throughout a lifetime (that is, memory persistence) emerges in early development across species. Although it has been shown that persistent fear memories emerge between late infancy and adolescence in mice, it is unclear exactly when this transition takes place, and whether two major fear conditioning…