The claustrum (Latin, meaning "to close" or "to shut") is a thin sheet of neurons and supporting glial cells in the brain that connects to the cerebral cortex and subcortical regions including the amygdala, hippocampus and thalamus. It is located between the insular cortex laterally and the putamen medially, encased by the extreme and external capsules respectively. Blood to the claustrum is supplied by the middle cerebral artery. It is considered to be the most densely connected structure in the brain, and thus hypothesized to allow for the integration of various cortical inputs such as vision, sound and touch, into one experience. Other hypotheses suggest that the claustrum plays a role in salience processing, to direct attention towards the most behaviorally relevant stimuli amongst the background noise. The claustrum is difficult to study given the limited number of individuals with claustral lesions and the poor resolution of neuroimaging.
The claustrum is made up of various cell types differing in size, shape and neurochemical composition. Five cell types exist, and a majority of these cells resemble pyramidal neurons found in the cortex. Within the claustrum, there is no laminar organization of cell types as in the cortical layers, and the cell bodies can be a pyramidal, fusiform or circular. The principal cell type found in the claustrum is the Golgi type I neuron, which is a large cell with dendrites covered in spines.
Through interhemispheric connections, the claustrum is believed to play a role in synchronizing activity in widely separated, but functionally related, parts of the brain such as between frontal eye fields and the visual cortex. As such, the claustrum is thought to play a role in combining different information modalities, potentially to support consciousness itself. Another proposed function of the claustrum is to differentiate between relevant and irrelevant information so that the latter can be ignored.
Cortical components of consciousness include the fronto-parietal cortex, cingulate and precuneus. Due to the claustrum's widespread connectivity to these areas, it is suggested that it may play a role in both attention and consciousness. The neural networks that mediate sustained attention and consciousness send inputs to the claustrum, and one case report in humans suggests that electrical stimulation near the claustrum reversibly disrupted the patient's conscious state.
Structure The claustrum is a small bilateral gray matter structure only a few tenths of a millimeter thick located deep to the insular cortex and extreme capsule, and superficial to the external capsule and basal ganglia. Despite this thinness, the claustrum spans more than 5 cm both anteroposteriorly and superoinferiorly. A 2026 histological reconstruction put its total volume at about 0.13% of the brain which is roughly twice that of the substantia nigra and three-quarters that of the amygdala.
Its name means "hidden away", and was first identified in 1672, with more detailed descriptions coming later on during the 19th century. Although the regional neuroanatomical boundaries of the claustrum have been defined, there remains a lack of consensus in the literature when defining its precise margins, though a meeting in 2019 of experts has posited a framework by which to refer to the structures across species.
Connections An early summary of reports from the 20th century emphasized cortical inputs and outputs. However, later work has suggested the claustrum has extensive connections to cortical and subcortical regions. More specifically, electrophysiological studies show extensive connections to thalamic nuclei and the basal ganglia, while isotopological reports have linked the claustrum with the prefrontal, frontal, parietal, temporal and occipital cortices. Additional studies have also looked at the relationship of the claustrum to well-described subcortical white matter tracts. Structures such as the corona radiata, occipitofrontal fasciculus and uncinate fasciculus project to the claustrum from frontal, pericentral, parietal and occipital regions. Reciprocal connections also exist with motor, somatosensory, auditory and visual cortical regions. Altogether, these findings leave the claustrum as the most highly connected structure per regional volume in the brain and suggest that it may serve as a hub to coordinate activity of cerebral circuits. Even with this extensive connectivity, most projections to and from the claustrum are ipsilateral (although there are still contralateral projections), and little evidence exists to describe its afferent or efferent connections with the brainstem and spinal cord. In summary, the cortical and subcortical connectivity of the claustrum implies that it is most involved with processing sensory information, as well as the physical and emotional state of an animal.
Microanatomy Inputs to the claustrum are organized by modality, which include prefrontal, visual, auditory and somatomotor processing areas. In the same way that the morphology of neurons in the Rexed laminae of the spinal cord is indicative of function, the visual, auditory and somatomotor regions within the claustrum share similar neurons with specific functional characteristics. For example, the portion of the claustrum that processes visual information (primarily synthesizing afferent fibers concerned with our peripheral visual field) is comprised by a majority of binocular cells that have "elongated receptive fields and no orientation selectivity".
This focus on the peripheral sensory system is not an isolated occurrence, as most sensory afferents entering the claustrum bring peripheral sensory information. Moreover, the claustrum possesses a distinct topological organization for each sensory modality as well as the dense connectivity it shares with frontal cortices. For example, there is a retinotopic organization within the visual processing area of the claustrum that mirrors that of visual association cortices and V1, in a similar (yet less complicated) manner to the retinotopic conservation within the lateral geniculate nucleus.
Within the claustrum, local connectivity is dominated by feed-forward disynaptic inhibition wherein parvalbumin-expressing interneurons suppress the activity of nearby projection neurons. Local interneurons themselves are connected through both chemical and electrical synapses, allowing for widespread and synchronous inhibition of local claustrum circuitry. In recent studies of the claustrum in mice and bats, cortically-projecting excitatory claustrum neurons were found to form synapses across the anteroposterior axis and were biased toward neurons that do not share projection targets, with the possible function of joining the activity of different afferent modules. Combined, these two circuits suggest that the claustrum is capable of performing local transformations of diverse input information from across the brain.
Cell types The claustrum is made up of various cell types that differ in size, shape and neurochemical composition. Excitatory cell types in the claustrum consist of two main classes which differentially project to cortical and subcortical brain regions. Inhibitory neurons represent only 10%-15% of the neurons within the claustrum and consist of three types, expressing parvalbumin, somatostatin or vasoactive intestinal peptide, similar to inhibitory neurons in the cortex. Finally, many studies show that the claustrum is best distinguished structurally by its prominent plexus of parvalbumin-positive fibers formed by parvalbumin-expressing inhibitory cell types. In recent studies, the use of myelin basic protein (MBP) and retrogradely traveling cholera toxin have additionally been used as effective methods of identifying the claustrum.
Several approaches in mice have been used to assess claustrum cell types, including electrophysiological, morphological, genetic, and connectomic approaches. While no clear consensus has yet been reached regarding the exact number of excitatory cell types, recent studies have suggested that cortically- and subcortically-projecting claustrum neurons are likely distinct and vary along several metrics, such as their intrinsic electrophysiological profiles, afferent projections, and neuromodulatory profiles.
Function The claustrum has been shown to have widespread activity to numerous cortical components, all of which have been associated with having components of consciousness and sustained attention. This is because of widespread connectivity to fronto-parietal areas, cingulate cortex, and thalami. Sustained attention is from the connections to the cingulate cortex, temporal cortex, and thalamus.
Crick and Koch suggest that the claustrum has a role similar to that of a conductor within an orchestra as it attempts to co-ordinate the function of all connections. This "conductor" analogy can also be supported through connections between the claustral, sensory, and frontal regions. The claustrum has been confirmed to be reciprocally connected to the prefrontal cortex, visual, auditory, sensory, and motor regions respectively. Connections to these modalities provide insight into the functionality of the claustrum. Here it is proposed that the claustrum functions in the gating of selective attention. Through this gating process the claustrum can selectively control input from these modalities to facilitate the process of "focusing". It has also been suggested that it operates in the opposite context; that through divisive normalization the claustrum may implement resistance to certain input modalities to prevent "distraction".
Potential function The claustrum, in order to facilitate consciousness, would need to integrate various sensory and motor modalities from various parts of the cortex. The anatomical connections of the claustrum have been observed using diffusion tensor imaging (DTI). A functional magnetic resonance imaging (fMRI) scan looks at oxygenated blood levels in the brain as a way of observing the activity of specific cortical areas. fMRI scans show dampened activity when anesthetized versus awake in rats, specifically claustrum connections to the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD thalamus). The claustrum is connected with the contralateral hemisphere's claustrum with strong, functional connections. Connections with MD thalamus, mPFC, and surrounding and distant cortical areas also exist.
Electrical stimulation in the dorsal claustrum of cats elicits excitatory responses within the visual cortex. The claustrum is situated anatomically at the confluence of a large number of white-matter tracts used to connect different parts of the cortex. This further suggests an integration center role for these different modalities, such as sensory and motor. Gap junctions have been shown to exist between aspiny (lacking dendrite projections) interneurons of the claustrum – suggesting a role in its ability to synchronize these modalities as input is received.
Additional studies point to involvement in spatial navigation and slow-wave sleep.
Attention The claustrum has the differential ability to select between task-relevant information and task-irrelevant information to provide directed attention. It contains the highest density of connecting white matter tracts in the cortex. This supports the notion of networking and coordination among different regions of the brain. The claustrum has regional specificity to it; information coming in from visual centers project to specific areas of grey matter neurons in the structure and the auditory cortex. Unexpected stimuli also activate the claustrum, effecting an immediate focusing or allocation of function. In lower mammals (e.g. rats), claustral regions receive input from somatosensory modalities, such as whiskers' motor control perspective because of its sensory and discriminatory use in these mammals.