scholarly journals Prelimbic-dependent activation of amygdala somatostatin interneurons signals non-aversive cues to promote discrimination

2020 ◽  
Author(s):  
J.M. Stujenske ◽  
P.K. O’Neill ◽  
I Nahmoud ◽  
S. Goldberg ◽  
L. Diaz ◽  
...  

AbstractThe amygdala and prelimbic cortex (PL) communicate during fear discrimination retrieval, but how they coordinate to discriminate a non-threatening stimulus is unknown. Here, we show that somatostatin interneurons (SOM) in the basolateral amygdala (BLA) become active specifically during learned non-threatening cues, when they block sensory-evoked phase resetting of theta-oscillations. Further, we show that SOM activation is PL-dependent, and promotes discrimination of non-threat. Thus, fear discrimination engages PL-dependent coordination of BLA SOM responses to non-threatening stimuli.

Author(s):  
Pantelis Antonoudiou ◽  
Phillip LW Colmers ◽  
Najah L Walton ◽  
Grant L Weiss ◽  
Anne C Smith ◽  
...  

AbstractBrexanolone (allopregnanolone), was recently approved by the FDA for the treatment of post-partum depression, demonstrating long-lasting antidepressant effects. Despite our understanding of the mechanism of action of neurosteroids as positive allosteric modulators (PAMs) of GABAa receptors, we still do not fully understand how allopregnanolone exerts these persistent antidepressant effects. Here, we demonstrate that allopregnanolone and similar synthetic neuroactive steroid analogs, SGE-516 (tool-compound) and zuranolone (SAGE-217, investigational-compound), are capable of modulating oscillatory states across species, which we propose may contribute to long-lasting changes in behavioral states. We identified a critical role for interneurons in generating oscillations in the basolateral amygdala (BLA) and a role for delta-containing GABAaRs in mediating the ability of neurosteroids to modulate network and behavioral states. Actions of allopregnanolone in the BLA is sufficient to alter behavioral states and enhance BLA high-theta oscillations (6-12Hz) through delta-containing GABAa receptors, a mechanism distinct from other GABAa PAMs, such as benzodiazepines. Moreover, treatment with the allopregnanolone analog SGE-516 induces long-lasting protection from chronic stress-induced disruption of network states, which correlates with improved behavioral outcomes. Our findings demonstrate a novel molecular and cellular mechanism mediating the well-established anxiolytic and antidepressant effects of neuroactive steroids.


2014 ◽  
Vol 1 (3) ◽  
pp. 140066 ◽  
Author(s):  
Masahiro Shibasaki ◽  
Tomoko Isomura ◽  
Nobuo Masataka

One of the most prevalent current psychobiological notions about human behaviour and emotion suggests that prioritization of threatening stimuli processing induces deleterious effects on task performance. In order to confirm its relevancy, 108 adults and 25 children were required to name the colour of images of snakes and flowers, using the pictorial emotional Stroop paradigm. When reaction time to answer the colour of each stimulus was measured, its value was found to decrease when snake images were presented when compared with when flower images were presented. Thus, contrary to the expectation from previous emotional Stroop paradigm research, emotions evoked by viewing images of snakes as a biologically relevant threatening stimulus were found to be likely to exert a facilitating rather than interfering effect on making judgements of their colour.


2021 ◽  
Author(s):  
Joshua W Maxwell ◽  
Lin Fang ◽  
Joshua Carlson

Threatening stimuli are often thought to have sufficient potency to capture spatial attentional resources over neutral stimuli. But few studies have examined if implicit factors like the selection history of the threatening stimulus influences such cases of capture. Here we tested whether capture by threat in the recent past (i.e., the previous trial) would carryover, or influence capture by threat in the present (i.e., the current trial). In two highly powered dot-probe experiments, we observed a small and a reverse capture effect (sometimes referred to as avoidance) for fearful faces (n = 241) and threatening images (n = 82), respectively. Critically, we found no evidence of carryover effects for either type of threatening stimuli. We conclude that within the standard dot-probe paradigm, capture by threat in healthy adults is not moderated by the selection history for threatening stimuli.


2019 ◽  
Vol 116 (14) ◽  
pp. 7077-7082 ◽  
Author(s):  
Areg Barsegyan ◽  
Gabriele Mirone ◽  
Giacomo Ronzoni ◽  
Chunan Guo ◽  
Qi Song ◽  
...  

Extensive evidence indicates that the basolateral amygdala (BLA) interacts with other brain regions in mediating stress hormone and emotional arousal effects on memory consolidation. Brain activation studies have shown that arousing conditions lead to the activation of large-scale neural networks and several functional connections between brain regions beyond the BLA. Whether such distal interactions on memory consolidation also depend on BLA activity is not as yet known. We investigated, in male Sprague–Dawley rats, whether BLA activity enables prelimbic cortex (PrL) interactions with the anterior insular cortex (aIC) and dorsal hippocampus (dHPC) in regulating glucocorticoid effects on different components of object recognition memory. The glucocorticoid receptor (GR) agonist RU 28362 administered into the PrL, but not infralimbic cortex, immediately after object recognition training enhanced 24-hour memory of both the identity and location of the object via functional interactions with the aIC and dHPC, respectively. Importantly, posttraining inactivation of the BLA by the noradrenergic antagonist propranolol abolished the effect of GR agonist administration into the PrL on memory enhancement of both the identity and location of the object. BLA inactivation by propranolol also blocked the effect of GR agonist administration into the PrL on inducing changes in neuronal activity within the aIC and dHPC during the postlearning consolidation period as well as on structural changes in spine morphology assessed 24 hours later. These findings provide evidence that BLA noradrenergic activity enables functional interactions between the PrL and the aIC and dHPC in regulating stress hormone and emotional arousal effects on memory.


2014 ◽  
Vol 25 (9) ◽  
pp. 2719-2728 ◽  
Author(s):  
Akira Uematsu ◽  
Akihiko Kitamura ◽  
Ken Iwatsuki ◽  
Hisayuki Uneyama ◽  
Tomokazu Tsurugizawa

2019 ◽  
Author(s):  
John Morris ◽  
Francois Windels ◽  
Pankaj Sah

AbstractThe partial reinforcement extinction effect (PREE) is a paradoxical learning phenomenon in which omission of reinforcement during acquisition results in more persistent conditioned responding in extinction. Here, we report a significant PREE with an inverted-U, entropy-like distribution against reinforcement probability following tone foot shock fear conditioning in rats, which was associated with increased neural activity in hippocampus and amygdala as indexed by p-ERK and c-fos immunolabelling. In vivo electrophysiological recordings of local field potentials (LFPs) showed that 50% reinforcement was associated with increases in the frequency and power of tone-evoked theta oscillations in both the subiculum region of hippocampus and in basolateral amygdala (BLA) during both acquisition (Day 1) and extinction (Day 2) sessions. Tone-evoked LFPs in 50% reinforced animals also showed increases in coherence and bidirectional Granger Causality between hippocampus and amygdala. The results support a Bayesian interpretation of the PREE, in which the phenomenon is driven by increases in the entropy or uncertainty of stimulus contingencies, and indicate a crucial role for hippocampus in mediating this uncertainty-dependent effect.


2019 ◽  
Vol 116 (52) ◽  
pp. 26970-26979 ◽  
Author(s):  
Heidi C. Meyer ◽  
Paola Odriozola ◽  
Emily M. Cohodes ◽  
Jeffrey D. Mandell ◽  
Anfei Li ◽  
...  

Heightened fear and inefficient safety learning are key features of fear and anxiety disorders. Evidence-based interventions for anxiety disorders, such as cognitive behavioral therapy, primarily rely on mechanisms of fear extinction. However, up to 50% of clinically anxious individuals do not respond to current evidence-based treatment, suggesting a critical need for new interventions based on alternative neurobiological pathways. Using parallel human and rodent conditioned inhibition paradigms alongside brain imaging methodologies, we investigated neural activity patterns in the ventral hippocampus in response to stimuli predictive of threat or safety and compound cues to test inhibition via safety in the presence of threat. Distinct hippocampal responses to threat, safety, and compound cues suggest that the ventral hippocampus is involved in conditioned inhibition in both mice and humans. Moreover, unique response patterns within target-differentiated subpopulations of ventral hippocampal neurons identify a circuit by which fear may be inhibited via safety. Specifically, ventral hippocampal neurons projecting to the prelimbic cortex, but not to the infralimbic cortex or basolateral amygdala, were more active to safety and compound cues than threat cues, and activity correlated with freezing behavior in rodents. A corresponding distinction was observed in humans: hippocampal–dorsal anterior cingulate cortex functional connectivity—but not hippocampal–anterior ventromedial prefrontal cortex or hippocampal–basolateral amygdala connectivity—differentiated between threat, safety, and compound conditions. These findings highlight the potential to enhance treatment for anxiety disorders by targeting an alternative neural mechanism through safety signal learning.


2020 ◽  
Vol 7 (4) ◽  
Author(s):  
Mina Mokhtari Hashtjini ◽  
Gila Pirzad Jahromi ◽  
Seyed Shahabeddin Sadr ◽  
Ali Khaleghi ◽  
Boshra Hatef ◽  
...  

Background: The study of the biological basis of fear in animal models has progressed considerably because of the energy and space that the brain devotes to this basic emotion. Electrical stimulation targets several structures of the brain to examine its behavioral effects and to understand the role of different regions in underlying mechanisms of fear processing and anxiety in preclinical models. Objectives: In this study, the effects of high-frequency deep brain stimulation (DBS) of the basolateral amygdala (BLA) and prelimbic (PL) sub-region of the prefrontal cortex were evaluated on the extinction process of conditioned fear. Methods: This study was performed on 35 male Wistar rats in the weight range of 220 – 250 g. After selecting the animals, they were separated into five groups. Then, we did stereotactic surgery on rats for electrode implantation. After recovery, some rats were conditioned, followed by a 10-day treatment schedule via high-frequency DBS in the BLA or PL. Next, freezing behavior was measured as a predicted response dedicated to extinction, without shock (re-exposure). In addition, we used ELISA and Western blot to estimate blood serum corticosterone levels and c-Fos protein expression. Results: The mean freezing time recorded for the PL group was significantly lower than that of both the BLA group and the PC group (P < 0.01). The BLA group and PC group were also significantly different (P < 0.001). Corticosterone results indicated that the PL group had significantly higher serum corticosterone levels compared with both the BLA group and the PC group (P < 0.01). In addition, the BLA group revealed a significant reduction in c-Fos expression compared with the PC (P < 0.001). Conclusions: This study provides further evidence for the contribution of the prelimbic cortex and amygdala both in acquisition and extinction processes during contextual fear conditioning. However, the PL stimulation by high-frequency DBS might be more involved in the extinction process and play a more important role as an enhancer.


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