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

Abstract

The claustrum is uniquely positioned to communicate with almost all higher-order cortical areas through widespread and reciprocal anatomical projections, yet the in vivo functional properties of claustrum neurons are not well understood. Here we use microendoscope imaging in mice to measure activity in populations of genetically-labelled Gnb4+ claustrum neurons. We find that only a small fraction of cells in the anterior claustrum are responsive to visual or auditory stimuli when delivered under passive yet wakeful conditions. In contrast, during a visual behavioral task, the majority of cells in the anterior claustrum are strongly modulated, with separate and spatially intermingled cell populations showing either increases or decreases in activity relative to spontaneous levels. Our results suggest that the Gnb4+ cells in the anterior claustrum do not represent passively presented sensory stimuli; rather, these cells are strongly engaged during behavior associated with sensory-motor transformations.

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

“…Moreover, we found CLA axons were frequently responsive during stimulation, implying the CLA actively participates during the processing of sensory information. This finding contrasts with recent studies in mice (49, 50) in which CLA neurons were infrequently responsive to sensory stimulation in vivo . The disparity between these results may be explained by methodological differences.…”

“…We thought that these responses may instead be related to attention, salience, or motor processes occurring as a result of the sensory stimulation, motivating our use of somatosensory and auditory stimuli despite weak direct inputs from these cortices, documented elsewhere 26,27 . The large proportion of activated axons contrasts with recent studies in mice 27,61 in which CLA neurons were infrequently responsive to sensory stimulation in vivo. The disparity between these results may be explained by methodological differences.…”

“…The finding that sham mice could discriminate between unimodal and multimodal stimuli while CLA-silenced animals could not implies that CLA activity may be specifically related to responding to the conjunction of sensory stimuli. While this may provide evidence that the CLA is involved in detecting the coincidence of audiovisual stimuli, there is still debate about whether this constitutes multisensory processing 6,26,27,29,61 . Therefore, careful examination of CLA activity during multisensory-guided behavior will be necessary in future experiments.…”

“…For these reasons, we found this method to be favorable over transgenic or viral labeling used in other studies (reviewed in 59 ; see also ref. 20,23,27,60,61 ). Retrograde tracing from RSP offered a simple method for accurately assessing the anatomical and physiological features of CLA neurons in later experiments.…”

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

“…The four different stimulation patterns were as follows: a single 5 ms pulse, a series of 5 ms pulses at 20 Hz or 40 Hz for 500 ms (10 and 20 pulses, respectively), and a prolonged step of 500 ms duration. The 5 ms pulse is a similar stimulation pattern to previous studies (Jackson et al, 2018;Narikiyo et al, 2020), while the 500 ms stimulation reflects the observation that CLA cells can become active for prolonged periods of time (100-500 ms) in a behavioral context (Chevée et al, 2021;Ollerenshaw et al, 2021). On average, we estimate that we stimulated 30-75% of CLA volume (Figure S1).…”