Opposing Influence of Basolateral Amygdala and Footshock Stimulation on Neurons of the Central Amygdala

2006 ◽  
Vol 59 (9) ◽  
pp. 801-811 ◽  
Author(s):  
J. Amiel Rosenkranz ◽  
Deanne M. Buffalari ◽  
Anthony A. Grace
2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ronald Sladky ◽  
Federica Riva ◽  
Lisa Anna Rosenberger ◽  
Jack van Honk ◽  
Claus Lamm

AbstractCooperation and mutual trust are essential in our society, yet not everybody is trustworthy. In this fMRI study, 62 healthy volunteers performed a repeated trust game, placing trust in a trustworthy or an untrustworthy player. We found that the central amygdala was active during trust behavior planning while the basolateral amygdala was active during outcome evaluation. When planning the trust behavior, central and basolateral amygdala activation was stronger for the untrustworthy player compared to the trustworthy player but only in participants who actually learned to differentiate the trustworthiness of the players. Independent of learning success, nucleus accumbens encoded whether trust was reciprocated. This suggests that learning whom to trust is not related to reward processing in the nucleus accumbens, but rather to engagement of the amygdala. Our study overcomes major empirical gaps between animal models and human neuroimaging and shows how different subnuclei of the amygdala and connected areas orchestrate learning to form different subjective trustworthiness beliefs about others and guide trust choice behavior.


2021 ◽  
Author(s):  
Ronald Sladky ◽  
Federica Riva ◽  
Lisa Rosenberger ◽  
Jack van Honk ◽  
Claus Lamm

Human societies are built on cooperation and mutual trust, but not everybody is trustworthy. Research on rodents suggests an essential role of the basolateral amygdala (BLA) in learning from social experiences (Hernandez-Lallement J et al., 2016), which was also confirmed in human subjects with selective bilateral BLA damage as they failed to adapt their trust behavior towards trustworthy vs. untrustworthy interaction partners (Rosenberger LA et al., 2019). However, neuroimaging in neurotypical populations did not consistently report involvement of the amygdala in trust behavior. This might be explained by the difficulty of differentiating between amygdala's structurally and functionally different subnuclei, i.e., the BLA and central amygdala (CeA), which have even antagonistic features particularly in trust behavior (van Honk J et al., 2013). Here, we used fMRI of the amygdala subnuclei of neurotypical adults (n=31f/31m) engaging in the repeated trust game. Our data show that both the BLA and the CeA play a role and indeed differentially: While the BLA was most active when obtaining feedback on whether invested trust had been reciprocated or not, the CeA was most active when subjects were preparing their next trust decision. In the latter phase, improved learning was associated with higher activation differences in response to untrustworthy vs. trustworthy trustees, in both BLA and CeA. Our data not only translate to rodent models and support our earlier findings in BLA-damaged subjects, but also show the specific contributions of other brain structures in the amygdala-centered network in learning whom to trust, and better not to trust.


2008 ◽  
Vol 100 (6) ◽  
pp. 3429-3436 ◽  
Author(s):  
Frank Z. Nagy ◽  
Denis Paré

The amygdala and bed nucleus of the stria terminalis (BNST) are thought to subserve distinct functions, with the former mediating rapid fear responses to discrete sensory cues and the latter longer “anxiety-like” states in response to diffuse environmental contingencies. However, these structures are reciprocally connected and their projection sites overlap extensively. To shed light on the significance of BNST–amygdala connections, we compared the antidromic response latencies of BNST and central amygdala (CE) neurons to brain stem stimulation. Whereas the frequency distribution of latencies was unimodal in BNST neurons (∼10-ms mode), that of CE neurons was bimodal (∼10- and ∼30-ms modes). However, after stria terminalis (ST) lesions, only short-latency antidromic responses were observed, suggesting that CE axons with long conduction times course through the ST. Compared with the direct route, the ST greatly lengthens the path of CE axons to the brain stem, an apparently disadvantageous arrangement. Because BNST and CE share major excitatory basolateral amygdala (BL) inputs, lengthening the path of CE axons might allow synchronization of BNST and CE impulses to brain stem when activated by BL. To test this, we applied electrical BL stimuli and compared orthodromic response latencies in CE and BNST neurons. The latency difference between CE and BNST neurons to BL stimuli approximated that seen between the antidromic responses of BNST cells and CE neurons with long conduction times. These results point to a hitherto unsuspected level of temporal coordination between the inputs and outputs of CE and BNST neurons, supporting the idea of shared functions.


2007 ◽  
Vol 87 (4) ◽  
pp. 1113-1173 ◽  
Author(s):  
Ewelina Knapska ◽  
Kasia Radwanska ◽  
Tomasz Werka ◽  
Leszek Kaczmarek

The amygdala is a heterogeneous brain structure implicated in processing of emotions and storing the emotional aspects of memories. Gene activity markers such as c-Fos have been shown to reflect both neuronal activation and neuronal plasticity. Herein, we analyze the expression patterns of gene activity markers in the amygdala in response to either behavioral training or treatment with drugs of abuse and then we confront the results with data on other approaches to internal complexity of the amygdala. c-Fos has been the most often studied in the amygdala, showing specific expression patterns in response to various treatments, most probably reflecting functional specializations among amygdala subdivisions. In the basolateral amygdala, c-Fos expression appears to be consistent with the proposed role of this nucleus in a plasticity of the current stimulus-value associations. Within the medial part of the central amygdala, c-Fos correlates with acquisition of alimentary/gustatory behaviors. On the other hand, in the lateral subdivision of the central amygdala, c-Fos expression relates to attention and vigilance. In the medial amygdala, c-Fos appears to be evoked by emotional novelty of the experimental situation. The data on the other major subdivisions of the amygdala are scarce. In conclusion, the studies on the gene activity markers, confronted with other approaches involving neuroanatomy, physiology, and the lesion method, have revealed novel aspects of the amygdala, especially pointing to functional heterogeneity of this brain region that does not fit very well into contemporarily active debate on serial versus parallel information processing within the amygdala.


2021 ◽  
Author(s):  
Nathan T Hall ◽  
Michael N Hallquist

Background: Borderline personality disorder (BPD) is associated with altered activity in the prefrontal cortex (PFC) and amygdala, yet no studies have examined fronto-limbic circuitry in borderline adolescents. Here, we examined the contribution of fronto-limbic connectivity to the longitudinal stability of emotion-related impulsivity (ERI), a key feature of BPD, in symptomatic adolescents and young adults. Methods: We compared resting-state effective connectivity (EC) in 82 adolescents and emerging adults with and without clinically significant borderline symptoms (n BPD = 40, ages 13-30). Group-specific directed networks were estimated amongst fronto-limbic nodes including PFC, ventral striatum (VS), central amygdala (CeN), and basolateral amygdala (BLA). We calculated directed centrality metrics and examined if these values were associated with initial levels and rates of change in ERI symptoms over a one-year follow-up using latent growth curve models (LGCMs). Results: In the healthy group, ventromedial prefrontal cortex (vmPFC) and dorsal ACC had a directed influence on CeN and VS respectively. In the borderline group bilateral BLA had a directed influence on CeN, whereas in the healthy group CeN influenced BLA. LGCMs revealed that in borderline adolescents, ERI remained stable across follow-ups. Further, higher output of R CeN in controls was associated with stronger within-person decreases in ERI. Conclusions: Functional inputs from BLA and vmPFC appear to play competing roles in influencing CeN activity. In borderline adolescents BLA may predominate over CeN activity, while in controls the ability of CeN to conversely influence BLA activity is associated with more rapid reductions in ERI.


2009 ◽  
Vol 101 (1) ◽  
pp. 341-349 ◽  
Author(s):  
Abolghasem Esmaeili ◽  
Joseph W. Lynch ◽  
Pankaj Sah

γ-Aminobutyric acid (GABA) is the primary inhibitory transmitter in the mammalian brain. This inhibition is mediated by type A (GABAA) receptors that are pentameric proteins assembled from 14 different subunits. Although inhibitory synaptic transmission has been studied in the amygdala, the subunit composition of receptors present at different synapses is not well understood. In this study we examined the subunit composition of GABAA receptors at synapses in the basolateral and central amygdala. Using receptors expressed in HEK293 cells we first determined the pharmacology of receptors of different subunit compositions. We then used this pharmacological profile to test the properties of receptors present at synapses in the central and basolateral amygdala. These results show that the GABAA receptor subunits are differentially distributed in the amygdala. Our data indicate that in the basolateral amygdala, GABAergic synapses are likely composed of receptors that contain α2βxγ2 subunits. In the central amygdala receptors at the medial input, carrying afferents from the bed nucleus of the stria terminalis contain similar receptors, whereas in the lateral input GABA receptors likely contain γ1 subunits. These inputs arise from the intercalated cells masses, thought to be responsible for mediating extinction of conditioned fear, raising the possibility of new targets for the treatment of anxiety-related disorders.


2021 ◽  
Author(s):  
Patricia Sampedro-Piquero ◽  
Roman Moreno-Fernandez ◽  
Azucena Begega ◽  
Matias Lopez ◽  
Luis J. Santin

Our aim was to assess the cognitive and emotional state, as well as related-changes in Glucocorticoid Receptor (GR), Corticotropin-Releasing Factor (CRF) and Brain-Derived Neurotrophic Factor (BDNF) expression of adolescent C57BL/6J male mice after a 5-week two-bottle choice protocol (postnatal day (pd) 21 to pd52). Additionally, we wanted to analyze whether the behavioral and neurobiological effects observed in the late adolescence (pd62) lasted until the adulthood (pd84). Behavioral testing revealed that alcohol during early adolescence increased anxiety-like and compulsive-related behaviors and it was maintained in the adulthood. Concerning cognition, working memory was only altered in late adolescent mice, whereas object location test performance was impaired in both ages. In contrast, novel object recognition remained unaltered. Immunohistochemical analysis showed that alcohol during adolescence diminished BDNF+ cells in the cingulate cortex, the hippocampal CA1 layer and the central amygdala. Regarding hypothalamic-pituitary-adrenal axis (HPA) functioning, alcohol abuse increased the GR and CRF expression in the hypothalamic paraventricular nucleus and the central amygdala. Besides, GR density was also higher in the prelimbic cortex and the basolateral amygdala regardless of animals age. Our findings suggest that adolescent alcohol exposure led to long-term behavioral alterations along with changes in BDNF, GR and CRF expression in limbic brain areas involved in stress response, emotional regulation, and cognition.


2021 ◽  
Author(s):  
behnam vafadari ◽  
shiladitya mitra ◽  
Leszek Kaczmarek

Abstract Stress, in particularly adolescence stress has been shown to result in long-term changes in brain and behavior of humans and rodents as well as predisposing individuals to multiple neuropsychiatric disorders like depression and schizophrenia. Stress-resulting in behavioral changes are often associated with structural changes of the neuronal dendritic spines, especially of the limbic system. Thus, analyzing alterations in structure of the dendritic spines in animals, which were subjected to adolescence stress, might provide useful information on pathogenesis of mental disorders. Herein, we analyzed the length, head width and area of dendritic spines of neurons from the hippocampal CA3, the central amygdala and the basolateral amygdala (BLA) regions in mature C57BL/6 mice, which were subjected to adolescent psychosocial stress. Results showed that stressed animals had longer spines in the hippocampus, larger spines in the BLA and shorter, smaller spines in the central amygdala (CeA). The latter finding is particularly intriguing, as it has been shown that central amygdala is not just the relay center for signals from the BLA in fear response, but is involved in antagonistic and inhibitory function to the BLA and active in appetitive and reward pathways.


Author(s):  
Donovan M Ashby ◽  
Carine Dias ◽  
Lily R Aleksandrova ◽  
Christopher C Lapish ◽  
Yu Tian Wang ◽  
...  

Abstract Background Latent inhibition (LI) reflects an adaptive form of learning impaired in certain forms of mental illness. Glutamate receptor activity is linked to LI, but the potential role of synaptic plasticity remains unspecified. Methods Accordingly, the present study examined the possible role of long-term depression (LTD) in LI induced by prior exposure of rats to an auditory stimulus used subsequently as a conditional stimulus to signal a pending footshock. We employed 2 mechanistically distinct LTD inhibitors, the Tat-GluA23Y peptide that blocks endocytosis of the GluA2-containing glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, or the selective glutamate n-methyl-d-aspartate receptor 2B antagonist, Ro25-6981, administered prior to the acquisition of 2-way conditioned avoidance with or without tone pre-exposure. Results Systemic LTD blockade with the Tat-GluA23Y peptide strengthened the LI effect by further impairing acquisition of conditioned avoidance in conditional stimulus-preexposed rats compared with normal conditioning in non-preexposed controls. Systemic Ro25-6981 had no significant effects. Brain region–specific microinjections of the Tat-GluA23Y peptide into the nucleus accumbens, medial prefrontal cortex, or central or basolateral amygdala demonstrated that disruption of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosis in the central amygdala also potentiated the LI effect. Conclusions These data revealed a previously unknown role for central amygdala LTD in LI as a key mediator of cognitive flexibility required to respond to previously irrelevant stimuli that acquire significance through reinforcement. The findings may have relevance both for our mechanistic understanding of LI and its alteration in disease states such as schizophrenia, while further elucidating the role of LTD in learning and memory.


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