Books by Lawrence Edelstein
Exosomes: A Clinical Compendium is a comprehensive and authoritative account of exosomes in the c... more Exosomes: A Clinical Compendium is a comprehensive and authoritative account of exosomes in the context of biomarkers, diagnostics and therapeutics across a wide spectrum of medical disciplines, as well as their role in cell-cell communication. It is intended to serve as a reference source for clinicians, physicians and research scientists who wish to gain insight into the most recent advances in this rapidly growing field.
The exosome revolution may well be the greatest advance in physiology and medicine since antibiotics. The discovery of their epigenetic role in intercellular signaling in virtually all tissues is a major breakthrough in our understanding of how cells function.
Key features
•Provides readers with a broad and timely overview of exosomes in health and disease, closing with a thought-provoking chapter on transgenerational inheritance, Darwin and Lamarck.
•Summarizes the most recent laboratory and clinical findings on exosomes across numerous medical disciplines, thereby offering readers a broad-ranging and solid foundation for prospective investigative efforts
•Twenty-one chapters authored by a global team of peer-acknowledged experts, each representing a key medical discipline
Claustrum
Larry Edelstein was the Editor-in-Chief of Claustrum (2016-2019), a peer-reviewed, open-access jo... more Larry Edelstein was the Editor-in-Chief of Claustrum (2016-2019), a peer-reviewed, open-access journal conceived as a nexus for all things pertaining to the claustrum. For more information, visit www.tandfonline.com/toc/zcla20/current.
Philosophical Transactions of the Royal Society B, Aug 18, 2014
Until recently, the computational role of the brain was mostly seen as a series of rapid electric... more Until recently, the computational role of the brain was mostly seen as a series of rapid electrical and electrochemical events, such as spike coding, local field potentials and EEG rhythms. To this was added the discovery some 20 years ago, pioneered by Eric Kandel, of a complex web of second messenger systems that translate synaptic activation into the local modulation of synaptically relevant protein synthesis by transcription factors such as CREB (cAMP response element binding proteins). The past decade has witnessed an even greater development in our understanding of how a wide swathe of the brain's functions is controlled, in this case by a further battery of epigenetic factors. These include DNA and histone methylation and acetylation that switch genes on and off, a wide range of transcription factors exported beyond the synapse that produced them, the activity of a multitude of non-coding RNAs (including the microRNAs that block mRNAs) and carrier organelles for these epigenetic loads, such as exosomes.
Exosomes are small lipoprotein vesicles that are known to bud-off from all cells and carry payloads of selected molecules. During the 1980s, it was thought that their function was simply to remove unwanted molecules—the ‘garbage can’ hypothesis. Then, it was discovered that they actually carry a wide assortment of nucleic acids and proteins, in particular, transcription factors and a variety of RNAs, which suggested that their true function is intercellular communication. This observation triggered an ever-increasing flood of papers, as it has become apparent that exosomes are involved in a very wide variety of cellular functions leading to radical new methods of diagnosis and therapy, with particular relevance for cancer. In the nervous system, they afford the organism critically important functions in the context of neuronal specification, plasticity and information processing.
This Theme Issue presents a series of 18 selected reviews and original research from peer-acknowledged experts in their respective disciplines on some of the highlights in this nascent and rapidly developing field. Some of these contributions present an overarching survey or a large segment of it, while others provide for a deep dive into a particular aspect. In the former category, Smalheiser [1] describes the role of exosomes in synaptic function and their orchestration of synaptic plasticity. Qureshi & Mehler [2] provide an overview of the staggering complexity of the epigenetic mechanisms thus far discovered in the brain. Imamura et al. [3] discuss the role of epigenetic regulation in neural cell reprogramming, engineering and transplantation. Roberts et al. [4] offer us a broad perspective of the putative role of long non-coding RNAs in neurodevelopment and brain function, with an emphasis on the epigenetic regulation of gene expression. The role of DNA modifications in the context of epigenetics, and more specifically with regard to the mammalian brain, is presented by Shin et al. [5]. An in-depth analysis of the role of microRNAs in synaptic plasticity and cognition, with a focus on neurological diseases, is given by Aksoy-Aksel et al. [6]. Prochiantz et al. [7] describe the remarkable role played by the transcription factors Otx2 and Engrained in the neuroplasticity of midbrain dopamine cell function and GABAergic cells in the visual cortex.
In 1786, the French anatomist Felix Vicq d’Azyr published his monumental in-folio treatise on the... more 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.
Papers by Lawrence Edelstein
Journal of Histotechnology, 2024
The aim of this study is to investigate whether the dorsal claustrum
receives afferent input from... more The aim of this study is to investigate whether the dorsal claustrum
receives afferent input from the intralaminar thalamic nuclei – centromedian nucleus, central lateral nucleus and paracentral nucleus. The intralaminar thalamic nuclei of eight cats were electrolytically lesioned. We obtained samples from the dorsal claustrum for electron microscopic analysis from the second to the seventh post-
procedural day. Two types of degenerated synaptic boutons were
observed: electron-dense which formed the majority of boutons, and electron-lucent comprising the remaining samples. Between the second and seventh post-procedural day, we observed a steady increase in the number of electron-dense boutons which were diffusely distributed throughout the dorsal claustrum. Electron-dense degenerated boutons formed asymmetrical contacts with dendritic spines as well as with small and medium-sized dendrites. In contrast, electron-lucent degenerated boutons were observed in earlier post-procedural periods and formed symmetrical axodendritic contacts.
Microscopy and Microanalysis, 2023
With current neuroanatomical molecular techniques, further insight has developed in terms of the ... more With current neuroanatomical molecular techniques, further insight has developed in terms of the Cl’s functional contributions. Even so, species differences and their analysis remain important. For example, one criticism of the Cl-consciousness hypothesis is that while all mammals may have a Cl, not all are believed to experience consciousness, at least in the context of the human experience. But perhaps this criticism misses the point. The Cl may indeed be functioning in the same way but differences in overall neuroanatomy (e.g., different patterns of cortical development) will result in physiologic and cognitive processes that do not lead to consciousness, per se. The Cl functions for the species-specific needs of a given animal through alternate types of information integration.
Journal of Molecular Histology, 2019
The claustrum is a subcortical nucleus, found in the telencephalon of all placental mammals. Earl... more The claustrum is a subcortical nucleus, found in the telencephalon of all placental mammals. Earlier Golgi studies have mostly focused on a qualitative description of the types of neurons. The aim of the present study was to describe the types of neurons found in the dorsal claustrum of the cat using the Golgi impregnation method and to perform a quantitative analysis of the following morphometric parameters: number of terminals (ends), total dendritic length, dendritic complexity, spine density (in spiny projection neurons), varicosity density (in aspiny interneurons). We used specimens from 5 healthy male cats stained according to the Golgi-Cox method. The dendritic trees of the studied neurons were then reconstructed through the Neurolucida software. Values of the studied quantitative parameters were obtained automatically and tested for statistically significant differences. Five types of spiny neurons were observed-large, medium-sized and small multipolar, bipolar and pyramidal-like. In addition, we described three types of aspiny neurons. The quantitative values and the statistical analysis were presented with tables and diagrams. In conclusion, we have presented a detailed analysis of the cytoarchitecture of the DC of the cat and have reported the first quantitative data on a number of morphometric parameters.
Acta Histochemica, 2019
The claustrum is a bilateral subcortical nucleus situated between the insular cortex and the stri... more The claustrum is a bilateral subcortical nucleus situated between the insular cortex and the striatum in the brain of all mammals. It consists of two embryologically distinct subdivisions-dorsal and ventral claustrum. The claustrum has high connectivity with various areas of the cortex, subcortical and allocortical structures. It has long been suggested that the various claustral connections have different types of synaptic contacts at the claustral neurons. However, to the best of our knowledge, the literature data on the ultrastructural organization of the different types of synaptic contacts in the dorsal claustrum are very few. Therefore, the aim of our study was to observe and describe the synaptic organization of the dorsal claustrum in the cat. We used a total of 10 adult male cats and conducted an ultrastructural study under a transmission electron microscope as per established protocol. We described a multitude of dendritic spines, which were subdivided into two types-with and without foot processes. Based on the size and shape of the terminal boutons, the quantity and distribution of vesicles and the characteristic features of the active synaptic zone, we described six types of synaptic boutons, most of which formed asymmetrical synaptic contacts. Furthermore, we reported the presence of axo-dendritic, axo-somatic, dendro-dendritic and axo-axonal synapses. The former two likely represent the morphological substrate of the corticoclaustral pathway, while the remaining two types have the ultrastructural features of inhibitory synapses, likely forming a local inhibitory circuit in the claustrum. In conclusion, the present study shares new information about the neuropil of the claustrum and proposes a systematic classification of the types of synaptic boutons and contacts observed in the dorsal claustrum of the cat, thus supporting its key and complex role as a structure integrating various information within the brain.
Claustrum, 2019
Background: The claustrum is the most densely connected brain structure by volume and has extensi... more Background: The claustrum is the most densely connected brain structure by volume and has extensive reciprocal connections with numerous cortical areas. It is divided into two embryologically distinct parts-dorsal and ventral claustrum. Despite numerous recent findings, much remains unknown about its structure and function.
Objective: The aim of our study was to observe and describe the ultrastructural characteristics of the different types of neurons in the dorsal claustrum of the cat and to discuss their possible functional significance.
Design: We used a total of 10 healthy young male cats. The obtained histological material was processed in the usual way for transmission electron microscopy.
Results: We observed four types of neurons in the dorsal claustrum of cats-large, medium-sized, small and 'dwarf' cells. While large and medium-sized neurons had a large electron-lucent nucleus with a wide cytoplasmic ring and an abundance of cellular organelles, small neurons had electron-lucent nuclei with varying degrees of dispersed and condensed chromatin and were poor in organelles. 'Dwarf' cells had the typical appearance of neurogliaform cells.
Conclusion: Based on their ultrastructural features, we recognized large and medium-sized neurons as efferent, or projection neurons. On the other hand, small neurons and neuroglia-form 'dwarf' cells had the typical ultrastructure of inhibitory interneurons.
Journal of Molecular Histology, 2018
The past decade has borne witness to an explosion in our understanding of the fundamental complex... more The past decade has borne witness to an explosion in our understanding of the fundamental complexities of intercellular communication. Previously, the field was solely defined by the simple exchange of endocrine, autocrine and epicrine agents. Then it was discovered that cells possess an elaborate system of extracellular vesicles, including exosomes, which carry a vast array of small and large molecules (including many epigenetic agents such as a variety RNAs and DNA), as well as large organelles that modulate almost every aspect of cellular function. In addition, it was thought that electrical communication between cells was limited mainly to neurotransmitters and neuromodulators in the nervous system. Also within the past decade, it was found that – in addition to neurons – most cells (both mammalian and non-mammalian) communicate via elaborate bioelectric systems which modulate many fundamental cellular processes including growth, differentiation, morphogenesis and repair. In the nervous system, volume transmission via the extracellular matrix has been added to the list. Lastly, it was discovered that what had previously been regarded as simple connective cells in most tissues proved to be miniature communication devices now known as telocytes. These unusually long, tenuous and sinuous cells utilize elaborate electrical, chemical and epigenetic mechanisms, including the exchange of exosomes, to integrate many activities within and between nearly all types of cells in tissues and organs. Their interrelationship with neural stem cells and neurogenesis in the context of neurodegenerative disease is just beginning to be explored. This review presents an account of precisely how each of these varied mechanisms are relevant and critical to the understanding of what telocytes are and how they function.
Journal of Chemical Neuroanatomy, 2017
A B S T R A C T We compared the distribution, density and morphological characteristics of nitric... more A B S T R A C T We compared the distribution, density and morphological characteristics of nitric oxide synthase-immunoreactive (NOS-ir) neurons in the rat and human claustrum. These neurons were categorized by diameter into three main types: large, medium and small. In the human claustrum, large neurons ranged from 26 to 40 mm in diameter, medium neurons from 20 to 25 mm and small neurons from 13 to 19 mm. In the rat claustrum, large neurons ranged from 19 to 23 mm in diameter, medium neurons from 15 to 18 mm and small neurons from 10 to 14 mm. The cell bodies of large and medium neurons varied broadly in shape – multipolar, elliptical, bipolar and irregular, consistent with a projection neuron phenotype. The small neurons were most seen as being oval or elliptical in shape, resembling an interneuron phenotype. Based on a quantitative comparison of their dendritic characteristics, the NOS-ir neurons of humans and rats displayed a statistically significant difference.
Claustrum, Feb 22, 2017
Background: The claustrum is present in all mammalian species. Many aspects of its morphology and... more Background: The claustrum is present in all mammalian species. Many aspects of its morphology and function remain subject to debate. It has been suggested that calcium-binding proteins influence neuronal activity in many structures. Objective: The aim was to examine CR immunoreactivity in the claustrum of guinea pigs and compare it with that in other mammals. Design: CR immunoreactivity in the claustrum was analyzed in five guinea pigs using immunohistochemical techniques. The distribution of CR-positive neurons in the dorsal claustrum and endopiriform nucleus (END), and their morphological characteristics were described. Results: CR immunostaining in the dorsal claustrum and END of the guinea pig consisted of CR-positive neurons, fibers, and puncta of varying labeling density. The majority of these neurons displayed small-or medium-sized round, oval, and multipolar cell bodies with aspiny dendrites. CR-ir neurons prevailed in the periphery of both divisions. The dorsal claustrum was seen to have a weakly CR-ir central core surrounded by a rim of moderately positive neuropil. Conclusion: CR immunoreactivity in the guinea pig claustrum was not as diffuse as in higher mammals, but non-uniformity was evident. CR-ir neurons are distributed in both the dorsal claustrum and END, mostly in the periphery.
Brain Structure and Function, Sep 19, 2017
Using the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reaction with nitroblu... more Using the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reaction with nitroblue tetrazolium, we provided a detailed investigation of the distribution, dimensional characteristics and morphology of NADPH-d-positive neurons in the three main subdivisions of the human inferior colliculus (IC): central nucleus, pericentral nucleus, and external nucleus. In accordance with their perikaryal diameter, dendritic and axonal morphology, these neurons were categorized as large (averaging up to 45 μm in diameter), medium (20-30 µm), small (13-16 µm) and very small (7-10 µm). Their morphological differences could contribute to varying functionality and processing capacity. Our results support the hypothesis that large and medium NADPH-d-positive cells represent projection neurons, while the small cells correspond to interneurons. Heretofore, the very small NADPH-d-positive neurons have not been described in any species. Their functions - and if they are indeed the smallest neurons in the IC of humans - remain to be clarified. Owing to their location, we posit that they are interneurons that connect the large NADPH-d-positive neurons and thereby serve as an anatomical substrate for information exchange and processing before feeding forward to higher brain centers. Our results also suggest that the broad distribution of nitric oxide (NO) synthesis in the human IC is closely tied to the neuromodulatory action of NO on collicular neurotransmitters such as GABA and glutamate, and to calcium-binding proteins such as parvalbumin. A deeper understanding of the relationship between NADPH-d-positive fibers in all IC connections and their colocalization with other neurotransmitters and calcium-binding proteins will assist in better defining the function of NO in the context of its interplay with the cerebral cortex, the sequelae of the aging process and neurodegenerative disorders.
Seminars in Cell & Developmental Biology, Mar 21, 2016
The past decade has borne witness to an explosion in our understanding of the fundamental complex... more The past decade has borne witness to an explosion in our understanding of the fundamental complexities of intercellular communication. Previously, the field was solely defined by the simple exchange of endocrine, autocrine and epicrine agents. Then it was discovered that cells possess an elaborate system of extracellular vesicles, including exosomes, which carry a vast array of small and large molecules (including many epigenetic agents such as a variety RNAs and DNA), as well as large organelles that modulate almost every aspect of cellular function. In addition, it was thought that electrical communication between cells was limited mainly to neurotransmitters and neuromodulators in the nervous system. Also within the past decade, it was found that – in addition to neurons – most cells (both mammalian and non-mammalian) communicate via elaborate bioelectric systems which modulate many fundamental cellular processes including growth, differentiation, morphogenesis and repair. In the nervous system, volume transmission via the extracellular matrix has been added to the list. Lastly, it was discovered that what had previously been regarded as simple connective cells in most tissues proved to be miniature communication devices now known as telocytes. These unusually long, tenuous and sinuous cells utilize elaborate electrical, chemical and epigenetic mechanisms, including the exchange of exosomes, to integrate many activities within and between nearly all types of cells in tissues and organs. Their interrelationship with neural stem cells and neurogenesis in the context of neurodegenerative disease is just beginning to be explored. This review presents an account of precisely how each of these varied mechanisms are relevant and critical to the understanding of what telocytes are and how they function.
Frontiers in Neuroanatomy, Jan 20, 2015
The claustrum is a telencephalic structure which consists of dorsal segment adjoining the insular... more The claustrum is a telencephalic structure which consists of dorsal segment adjoining the insular cortex and a ventral segment termed also endopiriform nucleus (END). The dorsal segment (claustrum) is divided into a dorsal and ventral zone, while the END is parcellated into dorsal, ventral and intermediate END. The claustrum and the END consist of glutamatergic projection neurons and GABAergic local interneurons coexpressing calcium binding proteins. Among neurons expressing calcium binding proteins the calretinin (CR)-immunoreactive interneurons exert specific functions in neuronal circuits, including disinhibition of excitatory neurons. Previous anatomical data indicate extensive and reciprocally organized claustral projections with cerebral cortex. We asked if the distribution of cells immunoreactive for CR delineates anatomical or functional subdivisions in the claustrum and in the END. Both segments of the claustrum and all subdivisions of the END contained CR immunoreactive neurons with varying distribution. The ventral zone of the claustrum exhibited weak labeling with isolated cell bodies and thin fibers and is devoid of immunoreactive puncta. Within the medial margin of the intermediate END we noted a group of strongly positive neurons. Cells immunoreactive for CR in all subdivisions of the claustrum and END were bipolar, multipolar and oval with smooth, beaded aspiny dendrites. Small number of CR-immunoreactive neurons displayed thin dendrites which enter to adjoining structures. Penetration of dendrites was reciprocal. These results show an inhomogenity over the claustrum and the END in distribution and types of CR immunoreactive neurons. The distribution of the CR-immunoreactive neurons respects the anatomical but not functional zones of the claustral complex.
Journal of Chemical Neuroanatomy, Aug 23, 2014
The claustrum is a telencephalic nucleus located ventrolateral to the basal ganglia in the mammal... more The claustrum is a telencephalic nucleus located ventrolateral to the basal ganglia in the mammalian brain. It has an extensive reciprocal connectivity with most if not all of the cerebral cortex, in particular, primary sensory areas. However, despite renewed and growing interest amongst investigators, there remains a paucity of data concerning its peptidergic profile. The aim of the present study was to examine the presence, morphology, distribution and ultrastructure of neuropeptide Y-immunoreactive (NPY-ir) neurons and fibers in the claustrum of the cat. Ten adult healthy cats from both sexes were used. All animals received human and ethical treatment in accordance with the Principles of Laboratory Animal Care. Subjects were irreversibly anesthetized and transcardially perfused with fixative solution containing glutaraldehyde and paraformaldehyde. Brains were promptly removed, postfixed and sectioned. Slices were incubated with polyclonal anti-NPY antibodies according to the standard avidin–biotin–peroxidase complex method adopted by our Department of Anatomy, Histology and Embryology. NPY-ir neurons and fibers were found to be diffusely distributed throughout the claustrum, with no obvious topographic or functional patterning other than larger numbers in its central/broadest part (stereotaxic planes A12–A16). Neurons were generally classified by diameter into three sizes: small (under 17 μm), medium (17–25 μm) and large (over 25 μm). Staining density is varied with some neurons appearing darker than others. At the electron-microscopic level NPY immunoproduct was observed within neurons, dendrites and terminal boutons, each differing relative to their ultrastructural attributes. Two types of NPY-ir synaptic boutons were found. Lastly, it is of interest to note that gender-specific differences were not observed.
![Research paper thumbnail of The role of epigenetic-related codes in neurocomputation: dynamic hardware in the brain [theme issue article]](https://attachments.academia-assets.com/34521185/thumbnails/1.jpg)
Philosophical Transactions of the Royal Society B, Aug 18, 2014
This paper presents a review of recent work on the role that two epigenetic related systems may p... more This paper presents a review of recent work on the role that two epigenetic related systems may play in information processing mechanisms in the brain. The first consists of exosomes that transport epigenetic-related molecules between neurons. The second consists of homeoproteins like Otx2 that carry information from sense organs to primary sensory cortex. There is developing evidence that presynaptic neurons may be able to modulate the fine microanatomical structure in the postsynaptic neuron. This may be conducted by three mechanisms, of which the first is well established and the latter two are novel. (i) By the well-established activation of receptors that trigger a chain of signalling molecules (second messengers) that result in the upregulation and/or activation of a transcription factor. The two novel systems are the exosome system and homeoproteins. (ii) Exosomes are small vesicles that are released upon activation of the axon terminal, traverse he synaptic cleft, probably via astrocytes and are taken up by the postsynaptic neuron. They carry a load of signalling proteins and a variety of forms of RNA. These loads may then be transported widely throughout the postsynaptic neuron and engineer modulations in the fine structure of computational machinery by epigenetic-related processes. (iii) Otx2 is a transcription factor that, inter alia, controls the development and survival of PV+GABAergic interneurons (PV cells) in the primary visual cortex. It is synthesized in the retina and is transported to the cortex by a presently unknown mechanism that probably includes direct cell-to-cell transfer, and may, or may not, include transfer by the dynein and exosome systems in addition. These three mechanisms explain a quantity of data from the field of de- and reafferentation plasticity. These data show that the modality of the presynaptic neuron controls to a large extent the modality of the postsynaptic neuron. However, the mechanism that effects this is currently unknown. The exosome and the homeoprotein hypotheses provide novel explanations to add to the well established earlier mechanism described above.
![Research paper thumbnail of Introduction - Epigenetic information-processing mechanisms in the brain [theme issue article]](https://attachments.academia-assets.com/34521162/thumbnails/1.jpg)
Philosophical Transactions of the Royal Society B, Aug 18, 2014
Until recently, the computational role of the brain was mostly seen as a series of rapid electric... more Until recently, the computational role of the brain was mostly seen as a series of rapid electrical and electrochemical events, such as spike coding, local field potentials and EEG rhythms. To this was added the discovery some 20 years ago, pioneered by Eric Kandel, of a complex web of second messenger systems that translate synaptic activation into the local modulation of synaptically relevant protein synthesis by transcription factors such as CREB (cAMP response element binding proteins). The past decade has witnessed an even greater development in our understanding of how a wide swathe of the brain’s functions is controlled, in this case by a further battery of epigenetic factors. These include DNA and histone methylation and acetylation that switch genes on and off, a wide range of transcription factors exported beyond the synapse that produced them, the activity of a multitude of non-coding RNAs (including the microRNAs that block mRNAs) and carrier organelles for these epigenetic loads, such as exosomes.
Frontiers in Molecular Neuroscience, Aug 4, 2014
A major activity at glutamatergic synapses in the brain is the production of potentially toxic ox... more A major activity at glutamatergic synapses in the brain is the production of potentially toxic oxygen radicals, in particular superoxide, by postsynaptic enzymes such as PGH synthase and by mitochondria. These need antioxidant mechanisms, such as the local production of antioxidant molecules (such as glutathione and ascorbate) and antioxidant enzymes, for protection of the neuron and its component chemicals (Smythies, 1999a,b). There may be also a further mechanism for antioxidant protection of neurons, that has been little explored, and that is the O'Brien cycle. This paper will describe this cycle and present an hypothesis as to its in vivo function.
Frontiers in Systems Neuroscience, May 27, 2014
We studied the topographical distribution and morphological characteristics of NADPH-diaphorase-p... more We studied the topographical distribution and morphological characteristics of NADPH-diaphorase-positive neurons and fibers in the human claustrum. These neurons were seen to be heterogeneously distributed throughout the claustrum. Taking into account the size and shape of stained perikarya as well as dendritic and axonal characteristics, Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd)-positive neurons were categorized by diameter into three types: large, medium and small. Large neurons ranged from 25 to 35 μm in diameter and typically displayed elliptical or multipolar cell bodies. Medium neurons ranged from 20 to 25 μm in diameter and displayed multipolar, bipolar and irregular cell bodies. Small neurons ranged from 14 to 20 μm in diameter and most often displayed oval or elliptical cell bodies. Based on dendritic characteristics, these neurons were divided into spiny and aspiny subtypes. Our findings reveal two populations of NADPHd-positive neurons in the human claustrum—one comprised of large and medium cells consistent with a projection neuron phenotype, the other represented by small cells resembling the interneuron phenotype as defined by previous Golgi impregnation studies.
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Books by Lawrence Edelstein
The exosome revolution may well be the greatest advance in physiology and medicine since antibiotics. The discovery of their epigenetic role in intercellular signaling in virtually all tissues is a major breakthrough in our understanding of how cells function.
Key features
•Provides readers with a broad and timely overview of exosomes in health and disease, closing with a thought-provoking chapter on transgenerational inheritance, Darwin and Lamarck.
•Summarizes the most recent laboratory and clinical findings on exosomes across numerous medical disciplines, thereby offering readers a broad-ranging and solid foundation for prospective investigative efforts
•Twenty-one chapters authored by a global team of peer-acknowledged experts, each representing a key medical discipline
Exosomes are small lipoprotein vesicles that are known to bud-off from all cells and carry payloads of selected molecules. During the 1980s, it was thought that their function was simply to remove unwanted molecules—the ‘garbage can’ hypothesis. Then, it was discovered that they actually carry a wide assortment of nucleic acids and proteins, in particular, transcription factors and a variety of RNAs, which suggested that their true function is intercellular communication. This observation triggered an ever-increasing flood of papers, as it has become apparent that exosomes are involved in a very wide variety of cellular functions leading to radical new methods of diagnosis and therapy, with particular relevance for cancer. In the nervous system, they afford the organism critically important functions in the context of neuronal specification, plasticity and information processing.
This Theme Issue presents a series of 18 selected reviews and original research from peer-acknowledged experts in their respective disciplines on some of the highlights in this nascent and rapidly developing field. Some of these contributions present an overarching survey or a large segment of it, while others provide for a deep dive into a particular aspect. In the former category, Smalheiser [1] describes the role of exosomes in synaptic function and their orchestration of synaptic plasticity. Qureshi & Mehler [2] provide an overview of the staggering complexity of the epigenetic mechanisms thus far discovered in the brain. Imamura et al. [3] discuss the role of epigenetic regulation in neural cell reprogramming, engineering and transplantation. Roberts et al. [4] offer us a broad perspective of the putative role of long non-coding RNAs in neurodevelopment and brain function, with an emphasis on the epigenetic regulation of gene expression. The role of DNA modifications in the context of epigenetics, and more specifically with regard to the mammalian brain, is presented by Shin et al. [5]. An in-depth analysis of the role of microRNAs in synaptic plasticity and cognition, with a focus on neurological diseases, is given by Aksoy-Aksel et al. [6]. Prochiantz et al. [7] describe the remarkable role played by the transcription factors Otx2 and Engrained in the neuroplasticity of midbrain dopamine cell function and GABAergic cells in the visual cortex.
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.
Papers by Lawrence Edelstein
receives afferent input from the intralaminar thalamic nuclei – centromedian nucleus, central lateral nucleus and paracentral nucleus. The intralaminar thalamic nuclei of eight cats were electrolytically lesioned. We obtained samples from the dorsal claustrum for electron microscopic analysis from the second to the seventh post-
procedural day. Two types of degenerated synaptic boutons were
observed: electron-dense which formed the majority of boutons, and electron-lucent comprising the remaining samples. Between the second and seventh post-procedural day, we observed a steady increase in the number of electron-dense boutons which were diffusely distributed throughout the dorsal claustrum. Electron-dense degenerated boutons formed asymmetrical contacts with dendritic spines as well as with small and medium-sized dendrites. In contrast, electron-lucent degenerated boutons were observed in earlier post-procedural periods and formed symmetrical axodendritic contacts.
Objective: The aim of our study was to observe and describe the ultrastructural characteristics of the different types of neurons in the dorsal claustrum of the cat and to discuss their possible functional significance.
Design: We used a total of 10 healthy young male cats. The obtained histological material was processed in the usual way for transmission electron microscopy.
Results: We observed four types of neurons in the dorsal claustrum of cats-large, medium-sized, small and 'dwarf' cells. While large and medium-sized neurons had a large electron-lucent nucleus with a wide cytoplasmic ring and an abundance of cellular organelles, small neurons had electron-lucent nuclei with varying degrees of dispersed and condensed chromatin and were poor in organelles. 'Dwarf' cells had the typical appearance of neurogliaform cells.
Conclusion: Based on their ultrastructural features, we recognized large and medium-sized neurons as efferent, or projection neurons. On the other hand, small neurons and neuroglia-form 'dwarf' cells had the typical ultrastructure of inhibitory interneurons.
The exosome revolution may well be the greatest advance in physiology and medicine since antibiotics. The discovery of their epigenetic role in intercellular signaling in virtually all tissues is a major breakthrough in our understanding of how cells function.
Key features
•Provides readers with a broad and timely overview of exosomes in health and disease, closing with a thought-provoking chapter on transgenerational inheritance, Darwin and Lamarck.
•Summarizes the most recent laboratory and clinical findings on exosomes across numerous medical disciplines, thereby offering readers a broad-ranging and solid foundation for prospective investigative efforts
•Twenty-one chapters authored by a global team of peer-acknowledged experts, each representing a key medical discipline
Exosomes are small lipoprotein vesicles that are known to bud-off from all cells and carry payloads of selected molecules. During the 1980s, it was thought that their function was simply to remove unwanted molecules—the ‘garbage can’ hypothesis. Then, it was discovered that they actually carry a wide assortment of nucleic acids and proteins, in particular, transcription factors and a variety of RNAs, which suggested that their true function is intercellular communication. This observation triggered an ever-increasing flood of papers, as it has become apparent that exosomes are involved in a very wide variety of cellular functions leading to radical new methods of diagnosis and therapy, with particular relevance for cancer. In the nervous system, they afford the organism critically important functions in the context of neuronal specification, plasticity and information processing.
This Theme Issue presents a series of 18 selected reviews and original research from peer-acknowledged experts in their respective disciplines on some of the highlights in this nascent and rapidly developing field. Some of these contributions present an overarching survey or a large segment of it, while others provide for a deep dive into a particular aspect. In the former category, Smalheiser [1] describes the role of exosomes in synaptic function and their orchestration of synaptic plasticity. Qureshi & Mehler [2] provide an overview of the staggering complexity of the epigenetic mechanisms thus far discovered in the brain. Imamura et al. [3] discuss the role of epigenetic regulation in neural cell reprogramming, engineering and transplantation. Roberts et al. [4] offer us a broad perspective of the putative role of long non-coding RNAs in neurodevelopment and brain function, with an emphasis on the epigenetic regulation of gene expression. The role of DNA modifications in the context of epigenetics, and more specifically with regard to the mammalian brain, is presented by Shin et al. [5]. An in-depth analysis of the role of microRNAs in synaptic plasticity and cognition, with a focus on neurological diseases, is given by Aksoy-Aksel et al. [6]. Prochiantz et al. [7] describe the remarkable role played by the transcription factors Otx2 and Engrained in the neuroplasticity of midbrain dopamine cell function and GABAergic cells in the visual cortex.
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.
receives afferent input from the intralaminar thalamic nuclei – centromedian nucleus, central lateral nucleus and paracentral nucleus. The intralaminar thalamic nuclei of eight cats were electrolytically lesioned. We obtained samples from the dorsal claustrum for electron microscopic analysis from the second to the seventh post-
procedural day. Two types of degenerated synaptic boutons were
observed: electron-dense which formed the majority of boutons, and electron-lucent comprising the remaining samples. Between the second and seventh post-procedural day, we observed a steady increase in the number of electron-dense boutons which were diffusely distributed throughout the dorsal claustrum. Electron-dense degenerated boutons formed asymmetrical contacts with dendritic spines as well as with small and medium-sized dendrites. In contrast, electron-lucent degenerated boutons were observed in earlier post-procedural periods and formed symmetrical axodendritic contacts.
Objective: The aim of our study was to observe and describe the ultrastructural characteristics of the different types of neurons in the dorsal claustrum of the cat and to discuss their possible functional significance.
Design: We used a total of 10 healthy young male cats. The obtained histological material was processed in the usual way for transmission electron microscopy.
Results: We observed four types of neurons in the dorsal claustrum of cats-large, medium-sized, small and 'dwarf' cells. While large and medium-sized neurons had a large electron-lucent nucleus with a wide cytoplasmic ring and an abundance of cellular organelles, small neurons had electron-lucent nuclei with varying degrees of dispersed and condensed chromatin and were poor in organelles. 'Dwarf' cells had the typical appearance of neurogliaform cells.
Conclusion: Based on their ultrastructural features, we recognized large and medium-sized neurons as efferent, or projection neurons. On the other hand, small neurons and neuroglia-form 'dwarf' cells had the typical ultrastructure of inhibitory interneurons.
This paper will explore two possible molecular mechanisms, based on microRNAs and exosomes, which may contribute to the inheritance of acquired characteristics. It will not be concerned directly with other mechanisms proposed in this field, such as the epigenetic reprogramming of the developing germ line, including epimutations, which may be responsible for some instances of inheritance. Stringer et al. (2013) have recently reviewed the Byzantine complexity of this field (also see Dias and Ressler, 2014). We propose to explore two additional (non-competitive) fields presented in the form of two hypotheses. The first involves short range exosome signaling and the second involves long range exosome signaling.
The authors explain this finding as follows: “We favor a model in which stellate neurons modulate activity and direct the local migration of neurons into barrels, modify gene expression, and influence cell morphologic development.” Li et al. (2013) present an hypothesis to explain their results; see also the preview of this paper by Barth and Kuhlman (2013). They suggest that it is possible that, by binding to its NMDA or metabotropic receptors, glutamate would stimulate second messenger chains that terminate by activating the appropriate transcription factors.
We accept their hypothesis as a partial explanation, but we suggest that there may be other factors involved that they have not considered. To explain these more fully we add two additional hypotheses. These hypotheses are not competitive, either with each other or with the original hypothesis of Li et al. (2013), but constitute additions.
Here we created lesions to the anterior claustrum of rats and tested performance on tasks that involve neural processing in one or more frontal or limbic cortical structures. The excitotoxin NMDA was used to create partial lesions to the anterior claustrum. Lesions were constrained to the claustrum except in a minority of subjects. Taking into account the fact that some of the highest densities of kappa-opioid receptors in the mammalian brain are in the claustrum, in a separate study we used a custom dynorphin-saporin conjugate supplied by Advanced Targeting Systems to create lesions.
We found that the claustral lesions using the targeted immunotoxin could be more complete than those provided by NMDA. In our first study, after excitotoxic lesions created by infusions of NMDA, we tested spatial reversal learning in a water maze. Lesioned rats were not impaired at acquiring the initial location of a goal platform in the maze, but were impaired at acquiring a switched location in the reversal phase. The lesioned rats also exhibited more perseverance errors compared to control rats during reversal. These same rats were not impaired at latent inhibition or working memory tasks, suggesting the effect of anterior claustral lesions may be related to behavioral flexibility.
This finding is consistent with theories of claustral function that suggest it may help coordinate information necessary for cortical-dependent tasks. We are currently assessing the role of the anterior claustrum on other measures of behavioral flexibility using a cohort of rats that have been subjected to immunotoxic lesions."
Objectives: The objectives of this study were to confirm the existence of nNOS-ir neurons and fibers in the human claustrum, employ light microscopy to describe their morphology and distribution, employ electron microscopy to describe and analyze their ultrastructure and synaptic architecture, verify whether they comprise a specific subpopulation of neurons, and establish whether they present with a specific pattern of organization.
Sample/Methods: Samples of claustrum were obtained from the brains of two females (39 and 48 years of age) and one male (63 years of age) at autopsy. The brains did not show any overt signs of pathology or trauma. The delay from death until fixation was 6-12 hours. Immunoreactivity to nNOS was assessed via the Avidin-Biotin Complex method.
Results: Light-microscopic analysis confirmed the presence of nNOS-ir neurons and fibers in all areas of the human claustrum, with neurons commonly found within a network of immunostained fibers. Cell bodies varied in shape and size, and were divided into three groups we’ve categorized as: small (35% of the sampled population, ‹19μm, but typically 13-17μm in diameter), medium (45%, 19-25μm in diameter), and large (20%, ›25μm in
diameter). The density of immunostaining varied both within and between cell types, with some neurons staining more darkly or lightly than others. Electron-microscopic analysis confirmed the presence of nNOS immunoproduct within neurons, dendrites and terminal boutons, with neurons further defined by their ultrastructural features. Three types of nNOS-ir synaptic boutons were noted. Additional information will be presented.
Conclusions: There are different types of nNOS-ir neurons within the human claustrum. The large- and medium-sized cells most likely correspond with claustrocortical projection neurons, while the small-sized cells appear to be inhibitory interneurons. It is our hope that these results contribute to a better understanding of the claustrum’s function in both health and disease, given its relationship with the development and sequelae of autism, schizophrenia, Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.
Objective: The objective of this study was to assess the distribution and morphological characteristics of NADPHd-positive cells in the human claustrum.
Sample/Methods: Samples of claustrum were obtained from the brains of two females (39 and 48 years of age) and one male (63 years of age) at autopsy. The brains did not show any overt signs of pathology or trauma. The delay from death until fixation was 6-12 hours. NADPHd histochemistry was employed, along with light and electron-microscopic analysis.
Results: NADPHd-positive neurons were irregularly distributed, often in clusters of 10 to 15. Very few positive neurons were observed adjacent to or in close proximity of the extreme and external capsules, or in the claustrum's most dorsal or caudal aspect. Reaction product diffusely filled the cytoplasm of positive neurons, while their nuclei remained stain-free. In many instances, cell staining was so intense that they resembled Golgi-impregnated neurons. These neurons were present throughout the claustrum, primarily in three sizes.
[1] Large neurons were 25-35µm in diameter, displaying multipolar, pyramidal, fusiform, elliptical, irregular, and oval soma. Each had 2-6 primary dendrites which branched into secondary and tertiary dendrites. The tertiary dendrites had an undulating course, radiating 700-900 µm from the soma. Their dendrites spread in all directions, some running parallel to the fibres of the extreme and external capsules. As a rule, they were aspiny, with the axon emanating from the perikaryon with a distinct hillock.
[2] Medium neurons were 19-25 µm in diameter, less common than the large type, and displayed round, multipolar or irregular soma, each with 3-4 dendrites with primary dendrites bifurcated or trifurcated into diverging secondary dendrites.
[3] Small neurons were 14-18 µm in diameter, with oval or elliptical soma, each with 3-4 dendrites. Primary dendrites were noted as being thin and varicose.
Conclusions: Our results provide additional insight into the distribution of NADPHd within the human claustrum. Given the critical importance of NADPHd in the context of neural transmission and its relationship to the etiology and sequelae of both Alzheimer’s and Huntington’s disease, it behooves us to investigate its presence in the claustrum, which has also been implicated in the development of these life-threatening disorders.
A complete and selective lesion of the claustrum is difficult to accomplish with standard methods due to its complex morphology and proximity to neighboring cortical structures. In rats however, the anterior section of the claustrum is vulnerable to experimental lesion. The rat anterior claustrum is located lateral to the forceps minor of the corpus callosum and medial to the ventral orbital cortex. At this location, the anterior claustrum is approximately 1 mm deep.
The densest connections of the anterior claustrum are with the nearby orbitofrontal, prefrontal, motor, and insular cortices. We damaged the anterior claustrum with infusions of 0.15 M NMDA (0.2 μl in each side) and tested performance on tasks that involve these cortical areas. Also, noting that some of the highest densities of kappa-opioid receptors in the mammalian brain are in the claustrum, we infused Dynorphin-Saporin (10 ng per side, with control rats receiving Blank-Saporin) with the expectation that larger and more complete lesions to the claustrum could be created.
We employed immunocytochemistry and morphometric analysis in
an effort to determine the distribution patterns and density of NMDA
receptors in the TRN of postnatal male and female rats.
These data support the contention that there are different types of NPY-containing neurons within the dorsal claustrum of the cat. Some, particularly the medium- and large-sized cells, likely correspond with projection neurons, while the small-sized cells appear to be interneurons. The definitive identification of these cell types requires the combined use of tract-tracing and immunocytochemical methods.
In the rat, it is ventrolateral to the caudate-putamen and connected with a
variety of cortical areas and subcortical structures. The cannabinoid type 1
receptor (CB1 receptor), a G protein-coupled receptor, is highly-expressed in
the mammalian brain and various other organs (e.g. lungs, liver and
kidneys). The CB1 receptor is intimately involved with the endocannabinoidmediated modulation of pain and stress via GABAergic signaling pathways.
The aim of this study was to investigate the effect of acute stress on
the distribution of CB1 receptors in the adult rat claustrum via
immunohistochemistry, as well as any influence it might have on the
synaptology and morphology of the cell bodies, dendrites and axons of
CB1-positive neurons.
nociception. On the other hand, Tyr-MIF-1 is a neuropeptide/neuromodulator, which is able to inhibit the expression of some forms of stress.
Activation of the endogenous opioid system plays a significant role in an animal’s response to stress. The neuropeptides Tyr-W-MIF-1 and Tyr-K-MIF-1 belong to the Tyr-MIF-1 peptide family. It is known that they bind to both non-opioid and µ-opioid receptors sites. Tyr-W-MIF-1 and Tyr-K-MIF-1 function as anti-opioid peptides (i.e. they decrease stress-induced analgesia).
we offer some preliminary results on the expression of parvalbumin (PV), neuropeptide-Y (NPY), calretinin (CR) and glial fibrillary acidic protein (GFAP) in the human dorsal claustrum.
family of calcium-binding proteins (CBPs), calcium-buffering proteins may act as modulators of cytosolic calcium levels. In several studies, a link was demonstrated between the expression of CBPs and neuronal excitability. The expression of CBPs is often used to reveal functionally different subdivisions of the CNS. Calretinin (CR) is a calcium-binding protein which binds calcium in a kinetically rapid fashion. In addition, CR is involved in the regulation of neuronal excitability and synaptic plasticity (Camp and Wijesinghe, 2009). Distribution of calcium-binding proteins in the CLD of the mouse is suggestive of the existence of calretinin-positive and -negative zones, which may reflect differences in their function and developmental origin (Real et al., 2003). The aim of this work is to obtain additional data specific to the distribution of CR in the rat and guinea pig claustrum, while searching for distribution patterns related to connectivity, functional characteristics and histogenetic parcellation.
modern neuroscience as it requires the application of both reductionist and
systems biology methods. Francis Crick’s writings on the subject place him in
the reductionist camp. Further, his willingness to hypothesize that a specific
brain nucleus, the claustrum (1), is important in understanding visual
consciousness, suggests that he applied a structure-function approach in an
attempt to bridge the two camps (2). This approach does not appeal to the
reductionists (for the level is not sufficiently molecular), nor is it the optimal
choice of systems biologists (for the concept of a foci is no longer in vogue).
So what makes this nucleus so special? Research has shown that the
claustrum is characterized by reciprocal and topographically-defined
relationships with most of neocortex (3). In this regard, the claustrum is
suitably positioned as a key element within a unique neural network, replete
with multisensory attributes (4), making it a viable candidate for contributing to
the establishment of visual consciousness. Perhaps Crick did not find a locus
of consciousness so much as the “server” as in a client-server relationship (to
use computing parlance). We include further information which highlights Dr.
Crick’s thoughts on the subject.