Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control

Cognitive abilities, such as volitional attention, operate under top-down, executive frontal cortical control of hierarchically lower structures. The circuit mechanisms underlying this process are unresolved. The claustrum possesses interconnectivity with many cortical areas and, thus, is hypothesized to orchestrate the cortical mantle for top-down control. Whether the claustrum receives top-down input and how this input may be processed by the claustrum have yet to be formally tested, however. We reveal that a rich anterior cingulate cortex (ACC) input to the claustrum encodes a preparatory top-down information signal on a five-choice response assay that is necessary for optimal task performance. We further show that ACC input monosynaptically targets claustrum inhibitory interneurons and spiny glutamatergic projection neurons, the latter of which amplify ACC input in a manner that is powerfully constrained by claustrum inhibitory microcircuitry. These results demonstrate ACC input to the claustrum is critical for top-down control guiding action., White et al. show that anterior cingulate cortex (ACC) input to the claustrum encodes a top-down preparatory signal on a 5-choice response assay that is critical for task performance. Claustrum microcircuitry amplifies top-down ACC input in a frequency-dependent manner for eventual propagation to the cortex for cognitive control of action.,

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(15/01/2024, 13:05:46 )

CLA connections and Top-down control

“The claustrum possesses interconnectivity with many cortical areas and, thus, is hypothesized to orchestrate the cortical mantle for top-down control.” (White et al., 2018, p. 84)

“Top-down cognitive processing is critical for identifying and responding to stimuli relating to reward in a largely irrelevant sensory world” (White et al., 2018, p. 84)

Proposal: CLA receive top down input for cognitive control

“the rat claustrum receives a dense innervation from the anterior cingulate cortex (ACC; White et al., 2017), an area implicated in top-down attention (Zhang et al., 2014, 2016), we hypothesize that the claustrum is positioned to receive top-down input for cognitive control (Mathur, 2014). Testing this, we found that ACC input to the mouse claustrum encodes an anticipatory top-down signal that is proportional to task load and required for optimal performance accuracy” (White et al., 2018, p. 84)

Relevance of top-down processes for Short Term Memory and CLA attention

“Top-down processing initiates in frontal executive cortices that modulate activity in downstream brain regions that are necessary for short-term memory and attention” (White et al., 2018, p. 84)

Bottom-up vs. Top-down

“However, it is unknown whether claustrum mediates top-down or bottom-up information ﬂow (Mathur, 2014), sits atop the information processing hierarchy to bind sensory information for conscious perception (Crick and Koch, 2005), or exists solely as a satellite processer for cortices (Olson and Graybiel, 1980)” (White et al., 2018, p. 84)

Anterior Cingulate Cortex (ACC) input to CLA relevant for cognitive control

“We further show that ACC input monosynaptically targets claustrum inhibitory interneurons and spiny glutamatergic projection neurons, the latter of which amplify ACC input in a manner that is powerfully constrained by claustrum inhibitory microcircuitry. These results demonstrate ACC input to the claustrum is critical for top-down control guiding action.” (White et al., 2018, p. 84)

Method

“To causally test a role for the ACC / claustrum circuit in 5CSRTT performance, we optogenetically manipulated this circuit using either viral expression of ChR2 (AAV-ChR2) or halorhodopsin (AAV-eNpHR3.0) in the ACC. Control mice solely expressed a ﬂuorophore in the ACC (AAV-enhanced yellow ﬂuorescent protein [AAV-eYFP]; Figure 3A). We conﬁrmed the placement of the ﬁber optic implant and light path in the claustrum post hoc (Figure 3B). We found that spiny projection neurons exhibited faithful activation in response to low-frequency (10-Hz) optogenetic stimulation of ACC afferents and a loss of AP generation in response to high-frequency (40-Hz) stimulation (Figure 3C).” (White et al., 2018, p. 86)

“Moreover, nose-poke accuracy is the only metric disrupted when mice were challenged with a visual distractor on 5CSRTT” (White et al., 2018, p. 88)

“These data demonstrate a circuit mechanism by which the claustrum ampliﬁes top-down inputs for the purpose of cognitive control over action.”

(White et al., 2018, p. 88)

CLA rather spreading Anterior Cingulate Cortex (ACC) input, not Sensory Cortex advocates for Top-down, not CLA sensory integration

“That the claustrum preferentially propagates input from ACC and not from sensorimotor cortices suggests that the claustrum is subservient to top-down circuit function rather than an integrator of sensory cortical information” (White et al., 2018, p. 88)

Possibly feedback to lower areas and also ACC

“It is possible that the claustrum may serve to propagate processed top-down input to cortical areas lower in the cortical hierarchy, such as visual cortex and parietal association cortex (PtA). Alternatively, the claustrum may primarily provide feedback to the ACC, consistent with a previously indicated view of claustrum (Olson and Graybiel, 1980)” (White et al., 2018, p. 88)

Fronto-parietal network during CLA attention and short term memory tasks

“If claustrum output coordinates frontal and parietal cortices, the claustrum may be a key node in the fronto-parietal network active during attention and short-term memory tasks” (White et al., 2018, p. 88)

Processing of salient visual stimuli in thalamic nuclei

“Thalamic nuclei, reciprocally connected with frontal and visual cortices, are critical for attention and working memory and direct connections between cortical areas enhance processing of salient visual stimuli” (White et al., 2018, p. 90)

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Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control