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Disrupted fear inhibition is a characteristic of many anxiety disorders. Investigations into the neural mechanisms responsible for inhibiting fear will improve understanding of the essential circuits involved, and facilitate development of treatments that promote their activity. Within the basolateral amygdala (BLA), Thy1-expressing neuron activity has been characterized by us and others as promoting fear inhibition to discrete fear cues by influencing consolidation of cued fear learning or cued fear extinction. Here, we evaluated how activating BLA Thy1-expressing neurons using DREADDs affected the consolidation, expression, reconsolidation, and extinction of contextual fear. Using an inhibitory avoidance paradigm, our present findings indicate a similar involvement of BLA Thy1-expressing neuron activity in the consolidation and extinction, but not expression, of fear. Importantly, our data also provide the first evidence for involvement of these neurons in inhibiting fear reconsolidation. Therefore, these data enhance our understanding of the roles that Thy1-expressing neurons within the BLA play in inhibiting fear when examining avoidance, in addition to the already established role in Pavlovian fear paradigms. Future investigations should further explore the circuits responsible for these contextual effects modulated by BLA Thy1 neuron activation, and could promulgate development of therapies targeting these neurons and their downstream effectors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Studies of social stress in adult mice have revealed two distinct defeat-responsive behavioral phenotypes; "susceptible" and "resistant," characterized by social avoidance and social interaction, respectively. Typically, these phenotypes are observed at least 1day after the last defeat in adults, but may extend up to 30days later. The current study examined the impact of peripubertal social defeat on immediate (1day) and adult (30day) social stress phenotypes and neuroendocrine function in male C57BL/6 mice. Initially, peripubertal (P32) mice were resistant to social defeat. When the same mice were tested for social interaction again as adults (P62), two phenotypes emerged; a group of mice were characterized as susceptible evidenced by significantly lower social interaction, whereas the remaining mice exhibited normal social interaction, characteristic of resistance. A repeated analysis of corticosterone revealed that the adult (P62) resistant mice had elevated corticosterone following the social interaction test as juveniles. This was when all mice, regardless of adult phenotype, displayed equivalent levels of social interaction. Peripubertal corticosterone was positively correlated with adult social interaction levels in defeated mice, suggesting early life stress responsiveness impacts adult social behavior. In addition, adult corticotropin-releasing factor (CRF) mRNA in the paraventricular nucleus of the hypothalamus (PVN) was elevated in all defeated mice, but there were no differences in CRF mRNA expression between the phenotypes. Thus, there is a delayed appearance of social stress-responsive phenotypes suggesting that early life stress exposure, combined with the resultant physiological responses, may interact with pubertal development to influence adult social behavior., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization., (Copyright © 2015 Elsevier Inc. All rights reserved.)