Role of the anterior agranular insular cortex in the modulation of fear and anxiety

Shi, Tianyao; Feng, Shini; Wei, Ming-Xiao; Zhou, Wenxia

doi:10.1016/j.brainresbull.2019.12.003

Cited by 38 publications

(35 citation statements)

References 43 publications

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“…Consistent with human studies, fear conditioning animal studies have shown that the activity of the insular cortex increases with fear 11 – 13 . In addition, ablations of the insular cortex induced anxiolytic behaviors and disrupted fear memory 14 – 16 , confirming the involvement of the insular cortex in fear. However, these studies mostly investigated the role of the posterior insular cortex.…”

Section: Introductionsupporting

confidence: 52%

Role of the anterior insular cortex in restraint-stress induced fear behaviors

Park

Cho

Huh

2022

Sci Rep

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Anxiety disorders, such as post-traumatic stress disorder (PTSD), are thought to occur by dysfunction in the fear and anxiety-related brain circuit, however, the exact mechanisms remain unknown. Recent human studies have shown that the right anterior insular cortex (aIC) activity is positively correlated with the severity of PTSD symptoms. Understanding the role of the aIC in fear and anxiety may provide insights into the etiology of anxiety disorders. We used a modified shock-probe defensive burying behavioral test, which utilizes the natural propensity of rodents to bury potentially dangerous objects, to test the role of aIC in fear. Mice exposed to restraint stress exhibited burying of the restrainer-resembling object, indicative of defensive behavior. Electrolytic ablation of the aIC significantly diminished this defensive burying behavior, suggesting the involvement of the aIC. Single-unit recording of pyramidal neurons in the aIC showed that a proportion of neurons which increased activity in the presence of a restrainer-resembling object was significantly correlated with the defensive burying behavior. This correlation was only present in mice exposed to restraint stress. These results suggest that altered neuronal representation in the aIC may regulate fear and anxiety after exposure to a traumatic event. Overall, our result demonstrates that the aIC mediates fear and anxiety and that it could be a potential target for treating anxiety disorders.

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Section: Introductionsupporting

confidence: 52%

Role of the anterior insular cortex in restraint-stress induced fear behaviors

Park

Cho

Huh

2022

Sci Rep

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“…However, a direct role of INS input to PL during fear memory consolidation has not been described before. This finding therefore supports a broader role for the INS in learning beyond taste-related tasks (Boughter & Fletcher, 2021;Shi et al, 2020).…”

Section: Discussionsupporting

confidence: 74%

Brain-wide screen of prelimbic cortex inputs reveals a functional shift during early fear memory consolidation

Dixsaut

Gräff

2022

Preprint

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Memory formation and storage rely on multiple interconnected brain areas, the contribution of which varies during memory consolidation. The medial prefrontal cortex, in particular the prelimbic cortex (PL), was traditionally found to be involved in remote memory storage, but recent evidence points towards its implication in early consolidation as well. Nevertheless, the inputs to the PL governing these dynamics remain unknown. Here, we first performed a brain-wide, rabies-based retrograde tracing screen of PL engram cells activated during contextual fear memory formation to identify relevant PL input regions. Next, we assessed the specific activity pattern of these inputs across different phases of memory consolidation, from fear memory encoding to recent and remote memory recall. Using projection-specific chemogenetic inhibition, we then tested their functional role in memory consolidation, which revealed a hitherto unknown contribution of claustrum to PL inputs at encoding, and of insular cortex to PL inputs at recent memory recall. Both of these inputs further impacted how PL engram cells were reactivated at memory recall, testifying to their relevance for establishing a memory trace in the PL. Collectively, this data identify a spatiotemporal shift in PL inputs important for early memory consolidation, and thereby help to refine the working model of memory formation.

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“…In the IC of mice, optogenetic inhibition of the posterior IC is anxiogenic [54], while inhibition of the anterior IC is anxiolytic in the EPM [55,56]. Posterior IC neurons also encode distinct emotional states, such as disgust and pleasure, that correlate with specific facial expressions [57].…”

Section: Box 3 Animal Behavioral Assays In Assessing Mood and Anxietmentioning

confidence: 99%

Circuit-Based Biomarkers for Mood and Anxiety Disorders

Xia

Kheirbek

2020

Trends in Neurosciences

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Mood and anxiety disorders are complex heterogeneous syndromes that manifest in dysfunctions across multiple brain regions, cell types, and circuits. Biomarkers using brain-wide activity patterns in humans have proven useful in distinguishing between disorder subtypes and identifying effective treatments. In order to improve biomarker identification, it is crucial to understand the basic circuitry underpinning brain-wide activity patterns. Leveraging a large repertoire of techniques, animal studies have examined roles of specific cell types and circuits in driving maladaptive behavior. Recent advances in multiregion recording techniques, data-driven analysis approaches, and machine-learning-based behavioral analysis tools can further push the boundary of animal studies and bridge the gap with human studies, to assess how brain-wide activity patterns encode and drive emotional behavior. Together, these efforts will allow identifying more precise biomarkers to enhance diagnosis and treatment. Distributed Neural Circuits Underly Mood and Anxiety Disorders Mood and anxiety disorders disrupt basic functions of individuals' lives, and are among the leading causes of disability [1]. In the USA, it is estimated that at a given timepoint, 10-20% of adults are impacted, and 20-30% of adults will experience a mood or anxiety disorder at some point in their lives (https://www.hcp.med.harvard.edu/ncs). However, most existing treatments are not effective [2,3]; largely due to a lack of clear understanding of disease etiology. The search for effective treatment is further complicated by the fact that mood and anxiety disorders are heterogeneous syndromes with various subtypes, where patients present diverse symptoms even for the same disorder, and often respond differently to the same treatment [4-7]. Highlights Mood and anxiety disorders are complex neural-circuit-based conditions that arise from dysfunctions across multiple cell types, brain regions, and circuits. Recent efforts in identifying circuit-based biomarkers using brain-wide activity patterns have shown promising results in stratifying disorder subtypes and identifying effective treatments for patients with mood and anxiety disorders.

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Role of the anterior agranular insular cortex in the modulation of fear and anxiety

Cited by 38 publications

References 43 publications

Role of the anterior insular cortex in restraint-stress induced fear behaviors

Role of the anterior insular cortex in restraint-stress induced fear behaviors

Brain-wide screen of prelimbic cortex inputs reveals a functional shift during early fear memory consolidation

Circuit-Based Biomarkers for Mood and Anxiety Disorders

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