The claustrum-medial prefrontal cortex network controls attentional set-shifting

Abstract

In various mental disorders, dysfunction of the prefrontal cortex contributes to cognitive deficits. Here we studied how the claustrum (CLA), a nucleus sharing reciprocal connections with the cortex, may participate in these cognitive impairments. We show that specific ensembles of CLA and of medial prefrontal cortex (mPFC) neurons are activated during a task requiring cognitive control such as attentional set-shifting, i.e. the ability to shift attention towards newly relevant stimulus-reward associations while disengaging from irrelevant ones. CLA neurons exert a direct excitatory input on mPFC pyramidal cells, and chemogenetic inhibition of CLA neurons suppresses the formation of specific mPFC assemblies during attentional set-shifting. Furthermore, impairing the recruitment of specific CLA assemblies through opto/chemogenetic manipulations prevents attentional set-shifting. In conclusion, we propose that the CLA controls the reorganization of mPFC ensembles to enable attentional set-shifting, emphasizing a potential role of the CLA-mPFC network in attentional dysfunctions.

Anterior claustrum cells are responsive during behavior but not passive sensory stimulation

“…More recent studies have associated the claustrum with many diverse functional and cognitive roles including sensory change detection (Remedios et al, 2014), top-down action control (White et al, 2020(White et al, , 2018, behavioral impulse control (Liu et al, 2019), navigation and spatial location coding (Jankowski and O'Mara, 2015), slow wave sleep (Narikiyo et al, 2020;Norimoto et al, 2020), attentional set shifting (Fodoulian et al, 2019), distractor suppression . CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

“…More recent studies have associated the claustrum with many diverse functional and cognitive roles including sensory change detection (Remedios et al, 2014), top-down action control (White et al, 2020, 2018), behavioral impulse control (Liu et al, 2019), navigation and spatial location coding (Jankowski and O’Mara, 2015), slow wave sleep (Narikiyo et al, 2020; Norimoto et al, 2020), attentional set shifting (Fodoulian et al, 2019), distractor suppression (Atlan et al, 2018), associative learning (Reus-garcía et al, 2020) and contextual association of reward (Terem et al, 2020). The diversity of functional properties measured in the claustrum could reflect spatially separate domains or cell types with distinct inputs.…”

“…In the mouse, there are numerous anatomical-genetic methods for labeling and expressing effector proteins in claustrum neurons, including viral injection (AAV) (Wang et al, 2017; White et al, 2020), retro-AAV injection into CLA projection areas (Jackson et al, 2018; Marriott et al, 2020; Zingg et al, 2018), CLA-Cre (Narikiyo et al, 2020), Egr2-Cre (Atlan et al, 2018; Terem et al, 2020), Esr2-Cre (Wang, 2019), D1-Cre (Terem et al, 2020), and Vglut2-Cre (Fodoulian et al, 2019). This results in a multiplicity of definitions of “claustrum neurons” and remains a challenge for the field.…”

Changing the Cortical Conductor’s Tempo: Neuromodulation of the Claustrum

“…Our answer begins with the simplified network, consisting of four pathways, shown in Figure 2A. Within a claustrocortical loop (Pathway 1), the claustrum may exert net inhibitory effects through feed-forward inhibition (FFI) that is mediated by claustrum excitation of local cortical interneurons (Ptito and Lassonde, 1981;Tsumoto and Suda, 1982;Salerno et al, 1984;Jackson et al, 2018;Narikiyo et al, 2020) and/or possibly net excitation, as suggested by more recent evidence (Fodoulian et al, 2020). This loop also includes excitatory monosynaptic input that claustral projection neurons and interneurons receive from various cortical regions (Kim et al, 2016;White and Mathur, 2018b;White et al, 2018;Chia et al, 2020); whether this combined input exerts a net inhibitory or excitatory effect on the claustrum remains unknown.…”

“…Recent findings have converged on a critical role for the claustrum in attention (Atlan et al, 2018;Fodoulian et al, 2020).…”