Interhemispheric resting-state functional connectivity of the claustrum in the awake and anesthetized states

Abstract

The claustrum is a brain region whose function remains unknown, though many investigators suggest it plays a role in conscious attention. Resting-state functional magnetic resonance imaging (RS-fMRI) has revealed how anesthesia alters many functional connections in the brain, but the functional role of the claustrum with respect to the awake versus anesthetized states remains unknown. Therefore, we employed a combination of seed-based RS-fMRI and neuroanatomical tracing to reveal how the anatomical connections of the claustrum are related to its functional connectivity during quiet wakefulness and the isoflurane-induced anesthetic state. In awake rats, RS-fMRI indicates that the claustrum has interhemispheric functional connections with the mediodorsal thalamus (MD) and medial prefrontal cortex (mPFC), as well as other known connections with cortical areas that correspond to the connections revealed by neuroanatomical tracing. During deep isoflurane anesthesia, the functional connections of the claustrum with mPFC and MD were significantly attenuated, while those with the rest of cortex were not significantly altered. These changes in claustral functional connectivity were also observed when seeds were placed in mPFC or MD during RS-fMRI comparisons of the awake and deeply anesthetized states. Collectively, these data indicate that the claustrum has functional connections with mPFC and MD-thalamus that are significantly lessened by anesthesia.

Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo

“…However, unlike prior studies, which largely relied on variations of depth of anesthesia, our comparison of awake states and anesthesia also suggested that the visual networks and their connectivity with default and frontoparietal networks actually showed anesthesia-related increases in connectivity. Overall, these findings echo recent studies of the impact of anesthetics on brain differences in humans, which suggested a loss of complexity in the functional architecture of the brain (Chang et al, 2016; Hutchison et al., 2014; Peltier et al, 2005; Smith et al, 2017; Wu et al, 2016). Further work will be required to rule out other possibilities, such as differences in respiration associated with differing states (awake or anesthesia).…”

“…Previous studies have demonstrated that FC patterns are sculpted more by structural connectivity under deep anesthesia than the awake state (Barttfeld and Uhrig, 2015; Wu et al, 2016). In anesthesia states, when isoflurane levels were varied, the signal fluctuations and connectivity also exhibited distinct profiles at each level within the same animal (Smith et al, 2017; Gao et al, 2017; Peltier et al, 2005; Hutchison et al., 2014). While it is expected that the parcels revealed will in many cases exhibit a gross similarity to traditionally defined neocortical areas, they are not intended to be 1:1.…”

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

“…The terminal boutons of claustrocortical projections are very small with a morphology that has been suggested to resemble “modulator” type synapses. As shown in the photomicrograph in Figure d, these terminals appear as small (<0.5 μm diameter), “mushroom‐like” boutons that extend off the axon (da Costa et al, ; Smith et al, ), which is consistent with “modulator” type synapses that exhibit paired‐pulse facilitation on their postsynaptic targets (Sherman & Guillery, ). However, there is some controversy surrounding the “driver/modulator” categorization for claustral synapses, especially for corticoclaustral synapses (Brown et al, ; Day‐Brown et al, ).…”

“…boutons that extend off the axon (da Costa et al, 2010;Smith et al, 2017), which is consistent with "modulator" type synapses that exhibit paired-pulse facilitation on their postsynaptic targets (Sherman & Guillery, 1998). However, there is some controversy surrounding the "driver/modulator" categorization for claustral synapses, especially for corticoclaustral synapses Day-Brown et al, 2017).…”

“…Similar circuit connections have also been observed more rostrally in the medial prefrontal cortex (mPFC). The mPFC projects most strongly to the contralateral CLA–DEn complex which, in turn, innervates the homotopic region of mPFC in that hemisphere and sends a collateral projection to other limbic‐associated cortical areas (Smith et al, ; Watson et al, ). Furthermore, a dorsoventral topography was observed such that dorsal mPFC (i.e., prelimbic cortex) has stronger connections with the CLA, whereas ventral mPFC (i.e., infralimbic cortex) innervates the DEn, a finding confirmed by other tracing studies (Behan & Haberly, ; Hoover & Vertes, ).…”