Influence of claustrum on cortex varies by area, layer, and cell type

Abstract

The claustrum is a small subcortical structure with widespread connections with disparate regions of the cortex. These far-reaching projections have led to many hypotheses concerning its function. However, we know little about how claustrum input affects neural activity in cortex, particularly beyond frontal areas. Here, using optogenetics and multi-regional Neuropixels recordings from over 15,000 neurons in awake mice, we demonstrate that the effect of claustrum input differs depending on brain area, layer, and cell type. Brief claustrum stimulation produces approximately 1 spike per claustrum neuron, which affects many fast-spiking (FS; putative inhibitory) but very few regular-spiking (RS; putative excitatory) cortical neurons. Prolonged claustrum stimulation affects many more cortical FS and RS neurons. More inhibition occurs in frontal regions and deeper layers, while more excitation occurs in posterior regions and superficial layers. These differences imply that the function of claustrum input to cortex depends on the area, supporting the idea that claustro-cortical circuits are organized into functional modules.

Single neurons and networks in the claustrum integrate input from widespread cortical sources

“…Our final set of experiments sought to investigate the regional and laminar differences of CLA innervation of the cortex as well as the types of sensory-related information CLA axons convey to their cortical targets. Recent in vivo electrophysiological evidence points toward differences in excitatory and inhibitory tone elicited by excitation of CLA cell bodies that varies by cortical area and layer (9, 51). Other studies in single cortical regions find more uniform responses to CLA inputs, generally inhibitory (73, 74), although electrophysiological studies in cats have found more variable or bidirectional responses in visual cortices (75, 76).…”

Regional and cell type-specific afferent and efferent projections of the mouse claustrum

“…Furthermore, perturbing the CLA-medial prefrontal pathway suggest that this pathway is involved in regulating impulsivity (Lui et al, 2019), attentional set-shifting (Fodoulian et al, 2020), and salience detection (Atlan et al, 2018; Terem et al, 2020), while optogenetic interrogating of the CLA-ACA pathway suggests that this pathway modulates engagement with the external world (Atlan et al, 2021). Optically activating CLA principal neurons of transgenic lines in the awake head-fixed mice on freely moving-wheel shows that neuronal responses differ in different layers and cell types of various cortical areas (prefrontal cortex, ACA, MOs and RSP) (McBride et al, 2022).…”

“…Our definition of the mouse CLA meets anatomical criteria and is consistent with a developmental study, which uses gene expression patterns to mark only one group of neurons underneath of the AI (Watson and Puelles, 2017), and with a combination of tract-tracing and immunohistochemical studies (Barbier et al,2019;Qadir et al, 2018;Suárez et al, 2018), similar to what has been used for rat CLA (Mathur et al, 2009(Mathur et al, , 2014. The accurate delineation of the boundary of the mouse CLA studies lays a solid foundation for a better understanding of its cell types, circuits, and functions as in the companion paper (McBride et al, 2022).…”

“…Different laminar distributions between claustrocortical projections and thalamocortical projections influence different cell types in the cortex (Brennan et al, 2021). It may be underly the mechanisms that neuron responses differ in cortical areas, layers and cell types after optical activating the CLA neurons (McBride et al, 2022)…”

“…The companion paper (McBride et al . 2022) studies the function of these CLA projection neurons in the same transgenic mouse lines by optogenetically exciting them and recording postsynaptic neurons in multiple cortical areas using Neuropixels electrodes.…”