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Nature Apr 2023Our understanding of the functions and mechanisms of sleep remains incomplete, reflecting their increasingly evident complexity. Likewise, studies of interhemispheric...
Our understanding of the functions and mechanisms of sleep remains incomplete, reflecting their increasingly evident complexity. Likewise, studies of interhemispheric coordination during sleep are often hard to connect precisely to known sleep circuits and mechanisms. Here, by recording from the claustra of sleeping bearded dragons (Pogona vitticeps), we show that, although the onsets and offsets of Pogona rapid-eye-movement (REM) and slow-wave sleep are coordinated bilaterally, these two sleep states differ markedly in their inter-claustral coordination. During slow-wave sleep, the claustra produce sharp-wave ripples independently of one another, showing no coordination. By contrast, during REM sleep, the potentials produced by the two claustra are precisely coordinated in amplitude and time. These signals, however, are not synchronous: one side leads the other by about 20 ms, with the leading side switching typically once per REM episode or in between successive episodes. The leading claustrum expresses the stronger activity, suggesting bilateral competition. This competition does not occur directly between the two claustra or telencephalic hemispheres. Rather, it occurs in the midbrain and depends on the integrity of a GABAergic (γ-aminobutyric-acid-producing) nucleus of the isthmic complex, which exists in all vertebrates and is known in birds to underlie bottom-up attention and gaze control. These results reveal that a winner-take-all-type competition exists between the two sides of the brain of Pogona, which originates in the midbrain and has precise consequences for claustrum activity and coordination during REM sleep.
Topics: Animals; Brain; Lizards; Mesencephalon; Sleep; Sleep, REM; Sleep, Slow-Wave; Functional Laterality; Time Factors; gamma-Aminobutyric Acid; Fixation, Ocular; Attention; Birds
PubMed: 36949193
DOI: 10.1038/s41586-023-05827-w -
Behavioral and Brain Functions : BBF Jul 2021The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious... (Review)
Review
INTRODUCTION
The claustrum is a structure involved in formation of several cortical and subcortical neural microcircuits which may be involved in such functions as conscious sensations and rewarding behavior. The claustrum is regarded as a multi-modal information processing network. Pathology of the claustrum is seen in certain neurological disorders. To date, there are not enough comprehensive studies that contain accurate information regarding involvement of the claustrum in development of neurological disorders.
OBJECTIVE
Our review aims to provide an update on claustrum anatomy, ontogenesis, cytoarchitecture, neural networks and their functional relation to the incidence of neurological diseases.
MATERIALS AND METHODS
A literature review was conducted using the Google Scholar, PubMed, NCBI MedLine, and eLibrary databases.
RESULTS
Despite new methods that have made it possible to study the claustrum at the molecular, genetic and epigenetic levels, its functions and connectivity are still poorly understood. The anatomical location, relatively uniform cytoarchitecture, and vast network of connections suggest a divergent role of the claustrum in integration and processing of input information and formation of coherent perceptions. Several studies have shown changes in the appearance, structure and volume of the claustrum in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), autism, schizophrenia, and depressive disorders. Taking into account the structure, ontogenesis, and functions of the claustrum, this literature review offers insight into understanding the crucial role of this structure in brain function and behavior.
Topics: Basal Ganglia; Claustrum; Cognition; Consciousness; Humans; Parkinson Disease
PubMed: 34233707
DOI: 10.1186/s12993-021-00181-1 -
Cell Reports May 2023Persistent pain is a prevalent medical concern correlating with a hyperexcitable anterior cingulate cortex (ACC). Its activity is modulated by inputs from several brain...
Persistent pain is a prevalent medical concern correlating with a hyperexcitable anterior cingulate cortex (ACC). Its activity is modulated by inputs from several brain regions, but the maladjustments that these afferent circuits undergo during the transition from acute to chronic pain still require clarification. We focus on ACC-projecting claustrum (CLA) neurons and their responses to sensory and aversive stimuli in a mouse model of inflammatory pain. Using chemogenetics, in vivo calcium imaging, and ex vivo electrophysiological approaches, we reveal that suppression of CLA activity acutely attenuates allodynia and that the claustrum preferentially transmits aversive information to the ACC. With prolonged pain, a claustro-cingulate functional impairment develops, which is mediated by a weakened excitatory drive onto ACC pyramidal neurons, resulting in a diminished claustral influence on the ACC. These findings support an instrumental role of the claustrum in the processing of nociceptive information and its susceptibility to persistent pain states.
Topics: Mice; Animals; Gyrus Cinguli; Neurons; Chronic Pain; Hyperalgesia
PubMed: 37182208
DOI: 10.1016/j.celrep.2023.112506 -
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 -
Frontiers in Neuroanatomy 2019The neural mechanisms of altered consciousness that accompanies most epileptic seizures are not known. We have reported alteration of consciousness resulting from... (Review)
Review
The neural mechanisms of altered consciousness that accompanies most epileptic seizures are not known. We have reported alteration of consciousness resulting from electrical stimulation of the claustrum a depth electrode in a woman with refractory focal epilepsy. Additionally, there are reports that suggest possible claustral involvement in focal epilepsy, including MRI findings of bilaterally increased T2 signal intensity in patients with status epilepticus (SE). Although its cytoarchitecture and connectivity have been studied extensively, the precise role of the claustrum in consciousness processing, and, thus, its contribution to the semiology of dyscognitive seizures are still elusive. To investigate the role of the claustrum in rats, we studied the effect of high-frequency stimulation (HFS) of the claustrum on performance in the operant chamber. We also studied the inter-claustral and the claustro-hippocampal connectivity through cerebro-cerebral evoked potentials (CCEPs), and investigated the involvement of the claustrum in kainate (KA)-induced seizures. We found that HFS of the claustrum decreased the performance in the operant task in a manner that was proportional to the current intensity used. In this article, we present previously unpublished data about the effect of stimulating extra-claustral regions in the operant chamber task as a control experiment. In these animals, stimulation of the corpus callosum, the largest interhemispheric commissure, as well as the orbitofrontal cortex in the vicinity of the claustrum did not produce that same effect as with claustral stimulation. Additionally, CCEPs established the presence of effective connectivity between both claustra, as well as between the claustrum and bilateral hippocampi indicating that these connections may be part of the circuitry involved in alteration of consciousness in limbic seizures. Lastly, some seizures induced by KA injections showed an early involvement of the claustrum with later propagation to the hippocampi. Further work is needed to clarify the exact role of the claustrum in mediating alteration of consciousness during epileptic seizures.
PubMed: 30809132
DOI: 10.3389/fnana.2019.00008 -
Brain, Behavior and Evolution 2022The author previously worked extensively on the broad problem of the evolution of the vertebrate pallium. He proposed various Bauplan models covering at least...
The author previously worked extensively on the broad problem of the evolution of the vertebrate pallium. He proposed various Bauplan models covering at least gnathostomes, based in the definition of a set of pallial sectors with topologically invariant positional relationships and distinct molecular profiles. Out of one of these models, presented as the "updated tetrapartite pallium model," a modified definition of the earlier lateral pallium sector (LPall) concept emerged, characterizing it in mammals as an unitary claustro-insular transitional (mesocortical) complex intercalated between the neocortex or dorsal pallium (DPall) above and olfactory cortex or ventral pallium (VPall) underneath. A distinctive molecular marker of the early-born deep claustral component of the LPall was found to be the transcription factor Nr4a2, which is not expressed significantly in the overlying insular cortex or in adjoining cortical territories. Given that earlier comparative studies had identified molecularly and topologically comparable VPall, LPall, and DPall sectors in the avian pallium, an avian Nr4a2 probe was applied, aiming to identify the reportedly absent avian claustro-insular complex. An early-born superficial subpopulation of the avian LPall that expresses this marker selectively through development was indeed found. This was proposed to be a claustrum homolog, whereas the remaining Nr4a2-negative avian LPall cells were assumed to represent a possible insular homolog. This last notion was subsequently supported by comparable selective expression of the mouse insular marker Cyp26b, also found restricted to the avian LPall. Some published data suggested that similar molecular properties and structure apply at the reptilian LPall. This analysis was reviewed in Puelles et al. [The pallium in reptiles and birds in the light of the updated tetrapartite pallium model. 2017]. Four years on, the present commentary discusses some international publications accrued in the interval that touch on the claustro-insular homology hypothesis. Some of them are opposed to the hypothesis whereas others corroborate or support it. This raises a number of secondary issues of general interest.
Topics: Animals; Birds; Mammals; Mice; Reptiles; Transcription Factors
PubMed: 34753135
DOI: 10.1159/000520742 -
Frontiers in Systems Neuroscience 2014The identity of the claustrum as a part of cerebral cortex, and in particular of the adjacent insular cortex, has been investigated by connectivity features and patterns...
The identity of the claustrum as a part of cerebral cortex, and in particular of the adjacent insular cortex, has been investigated by connectivity features and patterns of gene expression. In the present paper, we mapped the cortical and claustral expression of several cortical genes in rodent and macaque monkey brains (nurr1, latexin, cux2, and netrinG2) to further assess shared features between cortex and claustrum. In mice, these genes were densely expressed in the claustrum, but very sparsely in the cortex and not present in the striatum. To test whether the cortical vs. claustral cell types can be distinguished by co-expression of these genes, we performed a panel of double ISH in mouse and macaque brain. NetrinG2 and nurr1 genes were co-expressed across entire cortex and claustrum, but cux2 and nurr1 were co-expressed only in the insular cortex and claustrum. Latexin was expressed, in the macaque, only in the claustrum. The nurr1 (+) claustral neurons expressed VGluT1, a marker for cortical glutamatergic cells and send cortical projections. Taken together, our data suggest a partial commonality between claustral neurons and a subtype of cortical neurons in the monkey brain. Moreover, in the embryonic (E110) macaque brain, many nurr1 (+) neurons were scattered in the white matter between the claustrum and the insular cortex, possibly representing their migratory history. In a second set of experiments, we injected Lucifer Yellow intracellularly in mouse and rat slices to investigate whether dendrites of insular and claustral neurons can cross the border of the two brain regions. Dendrites of claustral neurons did not invade the overlying insular territory. In summary, gene expression profile of the claustrum is similar to that of the neocortex, in both rodent and macaque brains, but with modifications in density of expression and cellular co-localization of specific genes.
PubMed: 24904319
DOI: 10.3389/fnsys.2014.00098 -
Claustral MeCP2 Regulates Methamphetamine-induced Conditioned Place Preference in Cynomolgus Monkey.Experimental Neurobiology Dec 2022The claustrum, a brain nucleus located between the cortex and the striatum, has recently been highlighted in drug-related reward processing. Methyl CpG-binding protein-2...
The claustrum, a brain nucleus located between the cortex and the striatum, has recently been highlighted in drug-related reward processing. Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that represses or activates the expression of the target gene and has been known to have an important role in the regulation of drug addiction in the dopaminergic reward system. The claustrum is an important region for regulating reward processing where most neurons receive dopamine input; additionally, in this region, MeCP2 is also abundantly expressed. Therefore, here, we hypothesized that MeCP2 would be involved in drug addiction control in the Claustrum as well and investigated how claustral MeCP2 regulates drug addiction. To better understand the function of human claustral MeCP2, we established a non-human primate model of methamphetamine (METH) - induced conditioned place preference (CPP). After a habituation of two days and conditioning of ten days, the CPP test was conducted for three days. Interestingly, we confirmed that virus-mediated overexpression of MECP2 in the claustrum showed a significant reduction of METH-induced CPP in the three consecutive days during the testing period. Moreover, they showed a decrease in visit scores (frequency for visit) for the METH-paired room compared to the control group although the scores were statistically marginal. Taken together, we suggest that the claustrum is an important brain region associated with drug addiction, in which MeCP2 may function as a mediator in regulating the response to addictive drugs.
PubMed: 36631847
DOI: 10.5607/en22034 -
Neurochemical Research Jan 2020G protein-coupled receptors modulate the synaptic glutamate and GABA transmission of the claustrum. The work focused on the transmitter-receptor relationships in the...
G protein-coupled receptors modulate the synaptic glutamate and GABA transmission of the claustrum. The work focused on the transmitter-receptor relationships in the claustral catecholamine system and receptor-receptor interactions between kappa opioid receptors (KOR) and SomatostatinR2 (SSTR2) in claustrum. Methods used involved immunohistochemistry and in situ proximity ligation assay (PLA) using confocal microscopy. Double immunolabeling studies on dopamine (DA) D1 receptor (D1R) and tyrosine hydroxylase (TH) immunoreactivities (IR) demonstrated that D1R IR existed in almost all claustral and dorsal endopiriform nucleus (DEn) nerve cell bodies, known as glutamate projection neurons, and D4R IR in large numbers of nerve cell bodies of the claustrum and DEn. However, only a low to moderate density of TH IR nerve terminals was observed in the DEn versus de few scattered TH IR terminals found in the claustrum. These results indicated that DA D1R and D4R transmission in the rat operated via long distance DA volume transmission in the rat claustrum and DEn to modulate claustral-sensory cortical glutamate transmission. Large numbers of these glutamate projection neurons also expressed KOR and SSTR2 which formed KOR-SSTR2 heteroreceptor complexes using PLA. Such receptor-receptor interactions can finetune the activity of the glutamate claustral-sensory cortex projections from inhibition to enhancement of their sensory cortex signaling. This can give the sensory cortical regions significant help in deciding on the salience to be given to various incoming sensory stimuli.
Topics: Animals; Claustrum; Male; Neurotransmitter Agents; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, G-Protein-Coupled; Receptors, Opioid, kappa; Receptors, Somatostatin
PubMed: 31172348
DOI: 10.1007/s11064-019-02822-4 -
Brain and Neuroscience Advances 2017The claustrum is a highly conserved but enigmatic structure, with connections to the entire cortical mantle, as well as to an extended and extensive range of... (Review)
Review
The claustrum is a highly conserved but enigmatic structure, with connections to the entire cortical mantle, as well as to an extended and extensive range of heterogeneous subcortical structures. Indeed, the human claustrum is thought to have the highest number of connections per millimetre cubed of any other brain region. While there have been relatively few functional investigations of the claustrum, many theoretical suggestions have been put forward, including speculation that it plays a key role in the generation of consciousness in the mammalian brain. Other claims have been more circumspect, suggesting that the claustrum has a particular role in, for example, orchestrating cortical activity, spatial information processing or decision making. Here, we selectively review certain key recent anatomical, electrophysiological and behavioural experimental advances in claustral research and present evidence that calls for a reassessment of its anatomical boundaries in the rodent. We conclude with some open questions for future research.
PubMed: 32166134
DOI: 10.1177/2398212817718962