Mapping synaptic cortico‐claustral connectivity in the mouse

Abstract

The claustrum is an intriguing brain structure, featuring the highest connectivity per regional volume in the brain. It is a thin and elongated structure enclosed between the striatum and the insular cortex, with widespread reciprocal connections with the sensory modalities and prefrontal cortices. Retinotopic and somatotopic organizations have been described in the claustrum, and anatomical studies in cats, monkeys, and rats have demonstrated topographic organization of cortico-claustral connections. In this study we mapped the projections from cortical modalities (visual, auditory, somatosensory, motor, and olfactory), and prefrontal regions (anterior cingulate cortex and orbitofrontal cortex) to the claustrum in mice. Utilizing expression of a virally encoded synaptic anterograde tracer, AAV-SynaptoTag, followed by 3D reconstruction of the cortical projections, we performed a comprehensive study of the organization of these projections within the mouse claustrum. Our results clearly demonstrate a dorsoventral laminar organization of projections from the sensory cortices to the claustrum, whereas frontal inputs are more extensive and overlap with the inputs from the sensory cortices. In addition, we find evidence supporting a core/shell organization of the claustrum. We propose that the overlap between the frontal inputs and the inputs from the sensory modalities may underlie executive regulation of the communication between the claustrum and the cortical modalities. J. Comp. Neurol. 525:1381-1402, 2017. © 2016 Wiley Periodicals, Inc.

Input–output organization of the mouse claustrum

“…In particular, while most cortical input areas showed an ipsilateral bias in their projection to the CLA, cell body labeling was approximately equal in both hemispheres of the medial prefrontal cortex and was about 30% greater in the contralateral cingulate cortex (Figure b). This is in line with previous studies that have reported bilateral asymmetry in cortical projections to the CLA using retrograde (Smith & Alloway, ) and anterograde tracing methods (Atlan et al, ; Smith & Alloway, ; Wang et al, ). Together, these results suggest that cortical inputs to the CLA are highly convergent, as a wide variety of cortical regions provide synaptic input to a specific set of projection‐defined CLA cells.…”

“…Additionally, most input to the CLA arose from sources ipsilateral to the injection site, however about half of the input from mPFC and over 60% from ACA arose from the contralateral hemisphere. This is in agreement with previous observations reported with retrograde (Smith & Alloway, ) and anterograde tracing (Atlan et al, ; Smith & Alloway, ; Wang et al, ), however the functional significance of this bilateral asymmetry remains to be determined. It is interesting to note, as well, that such widespread presynaptic input, from nearly all of the potential sources implicated in previous studies (e.g., Wang et al, ), was observed for this projection‐defined population of starter cells.…”

The relationship between the claustrum and endopiriform nucleus: A perspective towards consensus on cross‐species homology

“…(a) Top panel shows the general topographic organization of CLA connections with cortex in rat, as identified by traditional retrograde tracing from cortex, which reveals a dorsal somatomotor area and a ventral visuoauditory area (modified from “Rat's claustrum shows two main cortico‐relate zones,” Sadowski et al, 1997, Brain Research, 756, p. 147–152). A similar topography is shown in mouse in the bottom panel, as mapped by modern viral tracing techniques, revealing olfactory bulb (allocortex) inputs to a more ventral region of CLA, likely DEn (modified from “Mapping synaptic cortico‐claustral connectivity in the mouse,” Atlan, Terem, Peretz‐Rivlin, Groysman, & Citri, , The Journal of Comparative Neurology, 525, p. 1381–1402). (b) Highly conserved dorsoventral topography in the primate CLA with somatomotor areas located in dorsal CLA, associative areas in central CLA, and visuoauditory areas located in ventral regions of CLA, as revealed by the horseradish peroxidase tracing method (modified from “The organization of the connections between the cortex and the claustrum in the monkey,” Pearson, Brodal, Gatter, & Powell, , Brain Research, 234(2), p. 435–441).…”

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

“…It is known that the claustrum is highly interconnected with many areas of cortex (Mathur, 2014; Crick and Koch, 2005; Torgerson et al, 2015; Mathur et al, 2009), including prefrontal, parietal, and visual cortices in monkey (Druga et al, 1990; Pearson et al, 1982; Reser et al, 2014; Riche and Lanoir, 1978; Tanné-Gariépy et al, 2002; Gattass et al, 2014; Ungerleider et al, 1984), as well as prelimbic and cingulate cortices of the rat (White et al, 2017; Wang et al, 2017; Atlan et al, 2017; Smith and Alloway, 2010; Smith et al, 2012). 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).…”