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Current Biology : CB Jul 2023The synthetic opioid fentanyl is a major contributor to the current opioid addiction crisis. We report that claustral neurons projecting to the frontal cortex limit oral...
The synthetic opioid fentanyl is a major contributor to the current opioid addiction crisis. We report that claustral neurons projecting to the frontal cortex limit oral fentanyl self-administration in mice. We found that fentanyl transcriptionally activates frontal-projecting claustrum neurons. These neurons also exhibit a unique suppression of Ca activity upon initiation of bouts of fentanyl consumption. Optogenetic stimulation of frontal-projecting claustral neurons, intervening in this suppression, decreased bouts of fentanyl consumption. In contrast, constitutive inhibition of frontal-projecting claustral neurons in the context of a novel, group-housed self-administration procedure increased fentanyl bout consumption. This same manipulation also sensitized conditioned-place preference for fentanyl and enhanced the representation of fentanyl experience in the frontal cortex. Together, our results indicate that claustrum neurons exert inhibitory control over frontal cortical neurons to restrict oral fentanyl intake. Upregulation of activity in the claustro-frontal projection may be a promising strategy for reducing human opioid addiction.
Topics: Mice; Humans; Animals; Claustrum; Analgesics, Opioid; Basal Ganglia; Frontal Lobe; Neurons; Fentanyl; Opioid-Related Disorders
PubMed: 37379841
DOI: 10.1016/j.cub.2023.05.065 -
Cell Reports Feb 2024Animals are known to exhibit innate and learned forms of defensive behaviors, but it is unclear whether animals can escape through methods other than these forms. In...
Animals are known to exhibit innate and learned forms of defensive behaviors, but it is unclear whether animals can escape through methods other than these forms. In this study, we develop the delayed escape task, in which male rats temporarily hold the information required for future escape, and we demonstrate that this task, in which the subject extrapolates from past experience without direct experience of its behavioral outcome, does not fall into either of the two forms of behavior. During the holding period, a subset of neurons in the rostral-to-striatum claustrum (rsCla), only when pooled together, sustain enhanced population activity without ongoing sensory stimuli. Transient inhibition of rsCla neurons during the initial part of the holding period produces prolonged inhibition of the enhanced activity. The transient inhibition also attenuates the delayed escape behavior. Our data suggest that the rsCla activity bridges escape-inducing stimuli to the delayed onset of escape.
Topics: Male; Animals; Rats; Claustrum; Corpus Striatum; Learning; Neostriatum; Neurons
PubMed: 38324450
DOI: 10.1016/j.celrep.2024.113748 -
PloS One 2024The claustrum is an irregular and fine sheet of grey matter in the basolateral telencephalon present in almost all mammals. The claustrum has been the object of several...
The claustrum is an irregular and fine sheet of grey matter in the basolateral telencephalon present in almost all mammals. The claustrum has been the object of several studies using animal models and, more recently, in human beings using neuroimaging. One of the most extended cognitive processes attributed to the claustrum is the salience process, which is also related to the insular cortex. In the same way, studies with human subjects and functional magnetic resonance imaging have reported the coactivation of the claustrum/insular cortex in the integration of sensory signals. This coactivation has been reported in the left claustrum/insular cortex or in the right claustrum/insular cortex. The asymmetry has been reported in task studies and literature related to neurological disorders such as Alzheimer's disease and schizophrenia, relating the severity of delusions with the reduction in left claustral volume. We present a functional connectivity study of the claustrum. Resting-state functional and anatomical MRI data from 100 healthy subjects were analyzed; taken from the Human Connectome Project (HCP, NIH Blueprint: The Human Connectome Project), with 2x2x2 mm3 voxel resolution. We hypothesize that 1) the claustrum is a node involved in different brain networks, 2) the functional connectivity pattern of the claustrum is different from the insular cortex's pattern, and 3) the asymmetry is present in the claustrum's functional connectivity. Our findings include at least three brain networks related to the claustrum. We found functional connectivity between the claustrum, frontoparietal network, and the default mode network as a distinctive attribute. The functional connectivity between the right claustrum with the frontoparietal network and the dorsal attention network supports the hypothesis of claustral asymmetry. These findings provide functional evidence, suggesting that the claustrum is coupled with the frontoparietal network serving together to instantiate new task states by flexibly modulating and interacting with other control and processing networks.
Topics: Animals; Humans; Claustrum; Connectome; Brain; Gray Matter; Cerebral Cortex; Magnetic Resonance Imaging; Mammals
PubMed: 38635579
DOI: 10.1371/journal.pone.0298349