Input–output organization of the mouse claustrum

Abstract

Progress in determining the precise organization and function of the claustrum has been hindered by the difficulty in reliably targeting these neurons. To overcome this, we used a projection-based targeting strategy to selectively label claustrum principal neurons. Combined with adeno-associated virus (AAV) and monosynaptic rabies tracing techniques, we systematically examined the pre-synaptic input and axonal output of this structure. We found that claustrum neurons projecting to retrosplenial cortex (RSP) collateralize extensively to innervate a variety of higher-order cortical regions. No subcortical labeling was found, with the exception of sparse terminals in the basolateral amygdala (BLA). This pattern of output was similar to cingulate- and visual cortex-projecting claustrum neurons, suggesting a common targeting scheme among these projection-defined populations. Rabies virus tracing directly demonstrated widespread synaptic inputs to RSP-projecting claustrum neurons from both cortical and subcortical areas. The strongest inputs arose from classically defined limbic regions, including medial prefrontal cortex, anterior cingulate, basolateral amygdala, ventral hippocampus, and neuromodulatory systems such as the dorsal raphe and cholinergic basal forebrain. These results suggest that the claustrum may integrate information related to the emotional salience of stimuli and may globally modulate cortical state by broadcasting its output uniformly across a variety of higher cognitive centers.

Gad1‐promotor‐driven GFP expression in non‐GABAergic neurons of the nucleus endopiriformis in a transgenic mouse line

“…Moreover, analysis of DiI labeling of cingulate cortex projection neurons revealed DiI‐positive fibers in close vicinity to GFP pos EPP neurons. Strong connectivity between the cingulate cortex and the claustrum–endopiriform complex was reported previously (Behan & Haberly, ; Condé et al, ; Qadir et al, ; Smith et al, ; Wang et al, ; Watson et al, ; White et al, ; Zingg et al, ), confirming our observations that these GFP pos neurons are located within the endopiriform nucleus. The endopiriform nucleus is strongly connected to the amygdaloid complex, therefore retrograde labeling of amygdalar projection neurons could further corroborate our finding that GFP pos neurons are located within the endopiriform nucleus (Majak et al, ).…”

“…In agreement with previous reports on PV expression in the nucleus endopiriformis (Real, Dávila, & Guirado, 2003;Wang et al, 2017), we only found scarce immunoreactivity to PV in the region with the highest density of GFP pos neurons (Figure 1b). Furthermore, previous studies reported on a strong connectivity between the claustrumendopiriform complex and the anterior cingulate and infralimbic cortex (Behan & Haberly, 1999;Condé, Maire-Lepoivre, Audinat, & Crépel, 1995;Qadir et al, 2018;Smith et al, 2018;Wang et al, 2017;White et al, 2017;Zingg, Dong, Tao, & Zhang, 2018). Therefore, we injected a DiI crystal into the anterior cingulate cortex and determined the presence of DiI-positive fibers in the area with the highest density of GFP pos neurons (Supporting Information Figure S2).…”

Brain-wide single neuron reconstruction reveals morphological diversity in molecularly defined striatal, thalamic, cortical and claustral neuron types

“…However, it remains largely unknown how population-level projection patterns are reflected at the single neuron level. Triple retrograde tracing studies suggest that individual neurons within a brain region often have heterogeneous axonal projection patterns [19][20][21] . Thus, characterizing single neuron axonal projections through reconstruction of complete morphologies not only provides critical information related to classifying cell types, but also how neural signals are organized and transmitted to their target regions.…”

What Is Old Is New Again: Investigating and Analyzing the Mysteries of the Claustrum

“…The analysis of the cellular composition, form, connectivity, and function of the claustrum represents a major challenge and here is where neuroinformatics can make an enormous contribution. With advances in the examination of brain connectivity in human 25 and in non-humans 26 and the availability of novel mathematical frameworks for analysis, 27 perhaps the next few years will see fuller computational and conceptual innovations for claustral characterization. 28 These may, finally, reveal a satisfying description of the claustrum and its role in cognition, conscious attention, and in clinical syndromes.…”