Neuromorphological Analysis of the Primate Claustrum

Cellular and Molecular Biology, 2004

The claustrum (Cl) is a subcortical structure located in the basolateral telencephalon of the mammalian brain. It has been a subject of inquiry since the mid-nineteenth century. The Cl can be identified in a number of species, and appears as a phylogenetically related nucleus in Insectivores, Prosimians and Marsupials. Ontogenetic investigations have been the subject of much debate over the years. There are three hypotheses for claustral development. To date, the "hybrid theory" has garnered the most support. Pathological conditions specifically associated with the Cl, while few in number, are of interest from a functional perspective. Several cases of claustral agenesis have been reported. The implications of these clinical reports are discussed. Claustral neuroanatomy at the lightmicroscopic and electron-microscopic level is reviewed. The morphology of the claustral neuron consists of several types, which roughly corresponds to the neuron's location within distinct claustral subdivisions. The interconnectivity of the Cl with the cerebral cortex is rather complex and reflective of complex functional interrelationships. Several researchers have investigated the angioarchitecture of the Cl. It appears that vessels permeating the insula also vascularize the Cl. Literature investigating the neurotransmitters and overall chemical neuroanatomy of the Cl is extensive. These studies clearly demonstrate that the Cl is richly innervated with a wide and diverse array of neurotransmitters and neuromodulators. Lesion, stimulation and recording experiments demonstrate that the functional and physiologic capacity of the Cl is quite robust. A recurring theme of claustral function appears to be its involvement in sensorimotor integration. This may be expected of the Cl, given the degree of heterotopic, heterosensory convergence and its interconnectivity with the key subcortical nuclei and sensory cortical areas. The Cl remains a poorly understood and under investigated nucleus. Therefore, a review of the world literature through 1986 prior to the advent of the "molecular revolution" is presented. This diverse and extensive body of knowledge is reviewed in the areas of phylogeny, ontogeny, pathology, angioarchitecture, cytochemistry, anatomy and physiology. Theories of possible claustral function are also noted. It is hoped that this work will stimulate research scientists to further investigate the functional interrelationships of the Cl as well as to aim with far greater precision and accuracy towards a deeper understanding of its raison d'etre. The recent efforts in neurosciences by Sir Francis Crick and Christof Koch implicating the Cl in visual consciousness, is an important step in understanding just what its functions could encompass. Efforts in molecular neurosciences will be indispensable for a mechanistic understanding of these functions. Currently research efforts are underway from many perspectives. In considering the past scientific literature on the Cl, it is interesting to regard that this once obscure brain structure, may serve as a model system for the study of one of the most interesting and complex brain functions -consciousness.

Journal of Comparative Neurology

With the emergence of interest in studying the claustrum, a recent special issue of the Journal of Comparative Neurology dedicated to the claustrum (Volume 525, Issue 6, pp. 1313-1513) brought to light questions concerning the relationship between the claustrum (CLA) and a region immediately ventral known as the endopiriform nucleus (En). These structures have been identified as separate entities in rodents but appear as a single continuous structure in primates. During the recent Society for Claustrum Research meeting, a panel of experts presented data pertaining to the relationship of these regions and held a discussion on whether CLA and En should be considered (1) separate unrelated structures, (2) separate nuclei within the same formation, or (3) subregions of a continuous structure. This review article summarizes that discussion, presenting comparisons of the cytoarchitecture, neurochemical profiles, genetic

2014

In 1786, the French anatomist Felix Vicq d’Azyr published his monumental in-folio treatise on the human brain, in which the claustrum was first identified. Macroscopically, it is a rather extensive yet thin sheet-like aggregate of neurons tucked beneath the insular cortex, sandwiched between the external and extreme capsules of the mammalian brain. Two-hundred-and-nineteen years later, Francis Crick and his colleague, Christof Koch, published their seminal paper entitled “What is the function of the claustrum?” (Crick and Koch, 2005). Their paper contains an extensive review of the existing anatomical and physiological data relating to the claustrum’s reciprocal connectivity with nearly all areas of the cerebral cortex, as well as many subcortical areas. In particular, they stressed the importance of there being far fewer claustral neurons (estimated at 16 million; Braak and Braak, 1982) than the 10 billion or so occupying the cerebral cortex (Shepherd, 1998). This results in a major convergence and condensation in the corticoclaustral pathway, and a corresponding divergence in the reciprocal claustrocortical pathway. Crick and Koch concluded that the claustrum is ideally situated with regard to its connectivity with each of the primary sensory cortices to best function as a neural correlate of consciousness, thereby serving to bind the never-ending influx of sensory information and return it from whence it came for higher-level processing demands in an efficient and energy-conserving manner. They further suggested that the claustrum supports “flows of information” in which GABAergic mechanisms play a prominent role. Additionally, they posited that claustral neurons could be “especially sensitive to the timing of neurons.” However, they did not offer any precise mechanisms to perform these functions. Our intention is to provide the neuroscience audience with what will be the first book solely devoted to the claustrum. In fact, to our knowledge, there are no other published efforts (either as a journal article, book chapter or symposium) which aim to provide their audience with such an all-encompassing and leading-edge perspective on this structure. The various topics to be covered in our book - each addressed in chapters written by highly regarded neuroscientists with substantive knowledge of the claustrum and related structures - are what one would expect from such an exhaustive undertaking. As well, we will offer a venue for the development of unifying hypotheses and critical insights from a variety of experts as to the claustrum’s role in consciousness, as well as the integration of sensory information and other higher brain functions. We have noticed a steadily growing interest in the areas of cross-modal processing and multisensory integration amongst the neuroscience, neurology and neuropsychiatric community, particularly as it relates to higher-level visual and auditory processing, as well as the investigation of neural correlates of consciousness. In addition, with the explosive growth and advances in the use of fMRI and DTI, the claustrum has been clearly implicated in the development and sequelae of such debilitating disorders as autism, schizophrenia, Alzheimer's disease, and Parkinson's disease. We believe that the time has come for a book which concisely compiles and organizes all of the extant information on this enigmatic yet highly understudied brain structure, at the same time providing its audience with the first comprehensively researched hypothesis as to its function, therein providing a platform and point of reference for future investigative efforts. We envision our readership to be neuroscientists, neurologists, neuropsychiatrists, neuropsychologists and advanced students, our intention being to bring basic researchers up to speed on all things claustral in one fell swoop, while simultaneously providing our collective audience with the first comprehensively researched and evaluated hypothesis as to its function.

Frontiers in systems neuroscience, 2014

We examined the pattern of retrograde tracer distribution in the claustrum following intracortical injections into the frontal pole (area 10), and in dorsal (area 9), and ventral lateral (area 12) regions of the rostral prefrontal cortex in the tufted capuchin monkey (Cebus apella). The resulting pattern of labeled cells was assessed in relation to the three-dimensional geometry of the claustrum, as well as recent reports of claustrum-prefrontal connections in other primates. Claustrum-prefrontal projections were extensive, and largely concentrated in the ventral half of the claustrum, especially in the rostral 2/3 of the nucleus. Our data are consistent with a topographic arrangement of claustrum-cortical connections in which prefrontal and association cortices receive connections largely from the rostral and medial claustrum. Comparative aspects of claustrum-prefrontal topography across primate species and the implications of claustrum connectivity for understanding of cortical fu...

Frontiers in Integrative Neuroscience, 2012

This paper presents a new hypothesis as to the function of the claustrum. Our basic premise is that the claustrum functions as a detector and integrator of synchrony in the axonal trains in its afferent inputs. In the first place, an unexpected stimulus sets up a processed signal to the sensory cortex that initiates a focus of synchronized gamma oscillations therein. This focus may then interact with a general alerting signal conveyed from the reticular formation via cholinergic mechanisms, and with other salient activations setup by the stimulus in other sensory pathways that are relayed to the cortex. This activity is relayed from the cortex to the claustrum, which then processes these several inputs by means of multiple competitive intraclaustral synchronized oscillations at different frequencies. Finally, it modulates the synchronized outputs that the claustrum distributes to most cortical and many subcortical structures, including the motor cortex. In this way, during multicenter perceptual and cognitive operations, reverberating claustro-cortical loops potentiate weak intracortical synchronizations by means of connected strong intraclaustral synchronizations. These may also occur without a salient stimulus. By this mechanism, the claustrum may play a strong role in the control of interactive processes in different parts of the brain, and in the control of voluntary behavior. These may include the neural correlates of consciousness. We also consider the role of GABAergic mechanisms and deafferentation plasticity.

Frontiers in Systems Neuroscience, 2014

The claustrum is a surprisingly large, sheet-like neuronal structure hidden beneath the inner surface of the neocortex. We found that the portions of the claustrum connected with V4 appear to overlap considerably with those portions connected with other cortical visual areas, including V1, V2, MT, MST and FST, TEO and TE. We found extensive reciprocal connections between V4 and the ventral portion of the claustrum (vCl), which extended through at least half of the rostrocaudal extent of the structure. Additionally, in approximately 75% of the cases, we found reciprocal connections between V4 and a more restricted region located farther dorsal, near the middle of the structure (mCl). Both vCl and mCl appear to have at least a crude topographic organization. Based on the projection of these claustrum subdivisions to the amygdala, we propose that vCl and mCl are gateways for the transmission of visual information to the memory system. In addition to these crude visuotopically organized regions, there are other parts of the claustrum that obey the topographical proximity principle, with considerable overlap of their connections. There is only an overall segregation of claustrum regions reciprocally connected to the occipital, parietal, temporal and frontal lobes. The portion of the claustrum connected to the visual cortex is located ventral and posterior; the one connected to the auditory cortex is located dorsal and posterior; the one connected to the somatosensory cortex is located dorsal and medial; the one connected to the frontal premotor and motor cortices is located dorsal and anterior; while the one connected to the temporal cortex is located ventral and anterior. The extensive reciprocal connections of the claustrum with almost the entire neocortex and its projections to the hippocampus, amygdala and basal ganglia prompt us to propose its role as a gateway for perceptual information to the memory system.

Understanding the claustrum’s functions has recently progressed thanks to new anatomical and behavioral studies in rodents, which suggest that it plays an important role in attention, salience detection, slow-wave generation, and neocortical network synchronization. Nevertheless, knowledge about the origin and development of the claustrum, especially in primates, is still limited. Here, we show that neurons of rhesus macaque claustrum primordium are generated between embryonic day E48 and E55 and express some neocortical molecular markers, such as NR4A2, SATB2, and SOX5. However, in the early stages, it lacks TBR1 expression, which separates it from other surrounding telencephalic structures. We also found that two waves of neurogenesis (E48 and E55) in the claustrum, corresponding to the birthdates of layers 6 and 5 of the insular cortex, establish a “core” and “shell” cytoarchitecture, which is potentially a basis for differential circuit formation and could influence information ...

The claustrum is present in all mammalian species examined so far and its morphology, chemoarchitecture, physiology, phylogenesis and ontogenesis are still a matter of debate. Several morphologically distinct types of immunostained cells were described in different mammalian species. To date, a comparative study on the neurochemical organization of the human and non-human primates claustrum has not been fully described yet, partially due to technical reasons linked to the postmortem sampling interval. The present study analyze the localization and morphology of neurons expressing parvalbumin (PV), calretinin (CR), NPY, and somatostatin (SOM) in the claustrum of man (# 5), chimpanzee (# 1) and crab-eating monkey (# 3). Immunoreactivity for the used markers was observed in neuronal cell bodies and processes distributed throughout the anterior-posterior extent of human, chimpanzee and macaque claustrum. Both CR-and PV-immunoreactive (ir) neurons were mostly localized in the central and ventral region of the claustrum of the three species while SOM-and NPY-ir neurons seemed to be equally distributed throughout the ventral-dorsal extent. In the chimpanzee claustrum SOM-ir elements were not observed. No co-localization of PV with CR was found, thus suggesting the existence of two non-overlapping populations of PV and CR-ir interneurons. The expression of most proteins (CR, PV, NPY), was similar in all species. The only exception was the absence of SOM-ir elements in the claustrum of the chimpanzee, likely due to species specific variability. Our data suggest a possible common structural organization shared with the adjacent insular region, a further element that emphasizes a possible common ontogeny of the claustrum and the neocortex.

WebmedCentral Neurosciences, 2012

Crick and Koch suggested in 2005 that the claustrum might be engaged in sensory binding operations related to consciousness. This might involve, they suggested, widespread waves of information traveling within the claustrum that might depend on networks of gap-junction linked neurons, which were especially sensitive to the timing of inputs. But they did not suggest any specific system to do this. The purpose of this present paper is to suggest what this mechanism might be. The basic thesis is that the claustrum is a spike coincidence–detecting device, constructed of large number of small simple identical nerve nets. These function as GABA-modulated ‘AND gates’ that convert the separate packets of unbound information in its inputs into an efferent signal that carries the binding information essential for consciousness and other brain functions. This function may also be relevant to processing of synchronized oscillation by the claustrum. Different anatomical regions of the claustrum may exert this function for sensory binding, computation of the significance of reinforcement in a complex environment, and other higher brain functions. We also suggest the outlines of a mechanism by which the cortex may process this input from the claustrum. We review the manner in which this hypothesis explains the present data. There is at present no other detailed hypothesis in this field. Key words: Claustrum, consciousness, binding, coincidence detection, AND gate, GABAergic interneurons, gap-junction linked networks, salvinorin A.

Brain structure & function, 2024

The claustrum is an ancient telencephalic subcortical structure displaying extensive, reciprocal connections with much of the cortex and receiving projections from thalamus, amygdala, and hippocampus. This structure has a general role in modulating cortical excitability and is considered to be engaged in different cognitive and motor functions, such as sensory integration and perceptual binding, salience-guided attention, top-down executive functions, as well as in the control of brain states, such as sleep and its interhemispheric integration. The present study is the first to describe in detail a projection from the claustrum to the striatum in the macaque brain. Based on tracer injections in different striatal regions and in different cortical areas, we observed a rough topography of the claustral connectivity, thanks to which a claustral zone projects to both a specific striatal territory and to cortical areas involved in a network projecting to the same striatal territory. The present data add new elements of complexity of the basal ganglia information processing mode in motor and non-motor functions and provide evidence for an influence of the claustrum on both cortical functional domains and cortico-basal ganglia circuits.