Annotations for: The Claustrum Supports Resilience to Distraction

✅ Key Points

• rationale [@atlanClaustrumSupportsResilience2018, p. 2752]

A barrage of information constantly assaults our senses, of which only a fraction is relevant at any given point in time. However, the neural circuitry supporting the suppression of irrelevant sensory distractors is not completely understood. [@atlanClaustrumSupportsResilience2018, p. 2752]

• what it does [@atlanClaustrumSupportsResilience2018, p. 2752]

Addressing the function of the claustrum, we inactivated CLEgr2+ neurons, [@atlanClaustrumSupportsResilience2018, p. 2752]

• test [@atlanClaustrumSupportsResilience2018, p. 2752]

neurons did not significantly impact task performance under varying delay times and cue durations, [@atlanClaustrumSupportsResilience2018, p. 2752]

• another test [@atlanClaustrumSupportsResilience2018, p. 2755]

Conducting the complementary experiment, we performed retrograde tracing by conditionally targeting pseudotyped rabies virus (pRbV) expression to CLEgr2+ starter cells, [@atlanClaustrumSupportsResilience2018, p. 2755]

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Background

Crick and Christof Koch, the next step in investigation of the claustrum, moving from correlation toward causation, requires genetic access to the claustrum, in order to perturb its function and address the role of this structure in behavior [5]. In the present study, we describe the identificatio [@atlanClaustrumSupportsResilience2018, p. 2752]

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Hypothesis

pup retrieval, we found that inactivating CLEgr2+ neurons selectively impacted the performance of mice upon introduction of a distractor, suggesting a specific r [@atlanClaustrumSupportsResilience2018, p. 2752]

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Methods

replicated the result of sensitization to an auditory distractor following inhibition of CLEgr2+ neurons. Initiating investigation into the underlying mechanism, we found that activation of CLEgr2+ [@atlanClaustrumSupportsResilience2018, p. 2752]

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Results

The need to identify and develop genetic tools that enable specific access to the claustrum has been emphasized for over a decade [5]. Even careful stereotactic targeting of non-conditional virus infection to the region of the claustrum is incapable of supporting selective access to claustral neurons due to the difficulty in precisely containing the spread of the virus to a thin and elongated structure. [@atlanClaustrumSupportsResilience2018, p. 2754]

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Implications

insula and claustrum in participants with attention deficit hyperactivity disorder compared to controls [12, 13]. In line with these findings are clinical observations from patients [@atlanClaustrumSupportsResilience2018, p. 2752]

• An illustration [@atlanClaustrumSupportsResilience2018, p. 2756]

Illustration of the automated behavioral setup for multiple animals in the homecage environment. The behavioral corner, connected to the homecage by a slim tube, contains two (left and right) ports, located beneath the cue lights. [@atlanClaustrumSupportsResilience2018, p. 2756]

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Further Reading

• test [@atlanClaustrumSupportsResilience2018, p. 2756]

Performance of mice following chronic silencing of CLEgr2+ neurons (Kir2.1) in comparison to control (GFP) mice, group averages ± SEM. Each point represents a single day, in chronological order. The delay time from trial initiation to cue presentation, as well as the duration of cue presentation, was progressively made more difficult (see also Figures S2C–S2J). [@atlanClaustrumSupportsResilience2018, p. 2756]

Annotations

(14/10/2023, 07:20:35 )

Here: using selective genetic access, the conclusion is “resilience to distraction”

“This functional study, utilizing selective genetic access, implicates the claustrum in supporting resilience to distraction, a fundamental aspect of attention.” (Atlan et al., 2018, p. 2752)

CLA salience: CLA inhibition mainly impacts when facing irrelevant (auditory) stimuli

“, inhibition of CLEgr2+ neurons did not significantly impact task performance under varying delay times and cue durations, but revealed a selective role for the claustrum in supporting performance in the presence of an irrelevant auditory distractor.” (Atlan et al., 2018, p. 2752)

“we found that activation of the claustrum suppressed auditory cortical responses to pure tone presentations.” (Atlan et al., 2018, p. 2759)

CLA connections: most interconnected structure

“The claustrum is reported to be the most interconnected brain structure per regional volume” (Atlan et al., 2018, p. 2752)

CLA connections: identified projections to subcortical structures (other than Mathur, 2014)

“We further extend the description of claustral afferents, identifying substantial projections to subcortical structures, notably nuclei in the midbrain, thalamus, striatum, amygdala, and basal forebrain” (Atlan et al., 2018, p. 2758)

CLA attention: possible interpretation as Top-down attention

“The role of the claustrum in maintaining goal-directed behavior in the presence of distraction could be interpreted in the context of top-down attention, a deficit of which is expected to selectively sensitize an affected animal to a distractor [56]. A recent study demonstrating a role for frontal inputs to the claustrum in top-down control [28] is consistent with our proposal that the claustrum acts to support resilience to distraction, a fundamental cognitive aspect of attention and sensory gating.” (Atlan et al., 2018, p. 2759)

CLA excitatory regulation: CLA “modulates cortical processing” “selectively diminishing the representation of sensory distractors, while retaining task-relevant sensory information”

“However, we favor the hypothesis that the claustrum modulates cortical processing in a refined manner, selectively diminishing the representation of sensory distractors, while retaining task-relevant sensory information” (Atlan et al., 2018, p. 2759)

Long lasting Claustro-cortical Feed-forward inhibition (e.g. CLA excitatory regulation)

“Recently, two reports describe powerful, widespread, and long-lasting feedforward inhibition of cortical activity driven by claustral neurons [58, 59]. Both groups, studying the impact of the claustrum on activity in frontal, association, and sensory cortical structures, describe an underlying mechanism whereby claustral neurons drive firing of cortical inhibitory interneurons, driving net inhibition of primary cortical neurons.” (Atlan et al., 2018, p. 2759)