Gerald M. Edelman's research while affiliated with The Neurosciences Institute and other places

Publications (267)

Article
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Recent evidence suggests that neurons in primary sensory cortex arrange into competitive groups, representing stimuli by their joint activity rather than as independent feature analysers. A possible explanation for these results is that sensory cortex implements attractor dynamics, although this proposal remains controversial. Here we report that f...
Article
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Mental imagery occurs ?when a representation of the type created during the initial phases of perception is present but the stimulus is not actually being perceived.? How does the capability to perform mental imagery arise? Extending the idea that imagery arises from learned associations, we propose that mental rotation, a specific form of imagery,...
Article
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In Alzheimer disease, elevated levels of the BACE1 enzyme are correlated with increased production of amyloid peptides and disease pathology. The increase in BACE1 levels is post-transcriptional and may involve altered translation efficiency. Earlier studies have indicated that translation of BACE1 mRNA is cap-dependent. As ribosomal subunits move...
Patent
A brain-based device (BBD) for moving in a real-world environment has sensors that provide data about the environment, actuators to move the BBD, and a hybrid controller which includes a neural controller having a simulated nervous system being a model of selected areas of the human brain and a non-neural controller based on a computational algorit...
Article
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Reentry in nervous systems is the ongoing bidirectional exchange of signals along reciprocal axonal fibers linking two or more brain areas. The hypothesis that reentrant signaling serves as a general mechanism to couple the functioning of multiple areas of the cerebral cortex and thalamus was first proposed in 1977 and 1978 (Edelman, 1978). A revie...
Article
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Animal behavior often involves a temporally ordered sequence of actions learned from experience. Here we describe simulations of interconnected networks of spiking neurons that learn to generate patterns of activity in correct temporal order. The simulation consists of large-scale networks of thousands of excitatory and inhibitory neurons that exhi...
Article
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We describe simulations of large-scale networks of excitatory and inhibitory spiking neurons that can generate dynamically stable winner-take-all (WTA) behavior. The network connectivity is a variant of center-surround architecture that we call center-annular-surround (CAS). In this architecture each neuron is excited by nearby neighbors and inhibi...
Article
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The Dynamic Core and Global Workspace hypotheses were independently put forward to provide mechanistic and biologically plausible accounts of how brains generate conscious mental content. The Dynamic Core proposes that reentrant neural activity in the thalamocortical system gives rise to conscious experience. Global Workspace reconciles the limited...
Article
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This paper presents an embodied approach to linking nervous system structure and function to behavior.
Article
mRNA-binding proteins are critical regulators of protein synthesis during neural development. We demonstrated previously that the cold-inducible mRNA-binding protein 3 (RBM3) is present within euthermic neurons and that it enhances translation. Other studies have attributed anti-apoptotic and proliferative functions to RBM3. Here we characterize th...
Article
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Epidemiological studies indicate that caffeine consumption reduces the risk of Parkinson's disease (PD) in men, and antagonists of the adenosine 2A receptor ameliorate the motor symptoms of PD. These findings motivated us to identify proteins whose expression is regulated by caffeine in a sexually dimorphic manner. Using mass spectroscopy, we found...
Article
In order to respond appropriately to environmental stimuli, organisms must integrate over time spatiotemporal signals that reflect object motion and self-movement. One possible mechanism to achieve this spatiotemporal transformation is to delay or lag neural responses. This paper reviews our recent modeling work testing the sufficiency of delayed r...
Chapter
classical instructive theories of antibody production;three-dimensional structure of the antigen;synthesis of the antibody molecule;cellular dynamics of the immune response;complementary binding sites
Article
The understanding of the structural and dynamic complexity of mammalian brains is greatly facilitated by computer simulations. We present here a detailed large-scale thalamocortical model based on experimental measures in several mammalian species. The model spans three anatomical scales. (i) It is based on global (white-matter) thalamocortical ana...
Article
Biologically based mobile devices have been constructed that differ from robots based on artificial intelligence. These brain-based devices (BBDs) contain simulated brains that autonomously categorize signals from the environment without a priori instruction. Two such BBDs, Darwin VII and Darwin X, are described here. Darwin VII recognizes objects...
Conference Paper
Without a doubt the most sophisticated behavior seen in biological agents is demonstrated by organisms whose behavior is guided by a nervous system. Thus, the construction of behaving devices based on principles of nervous systems may have much to offer. Our group has built series of brain-based devices (BBDs) over the last fifteen years to provide...
Article
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The ribosome filter hypothesis postulates that ribosomes are not simply translation machines but also function as regulatory elements that differentially affect or filter the translation of particular mRNAs. On the basis of new information, we take the opportunity here to review the ribosome filter hypothesis, suggest specific mechanisms of action,...
Article
We describe a theoretical network analysis that can distinguish statistically causal interactions in population neural activity leading to a specific output. We introduce the concept of a causal core to refer to the set of neuronal interactions that are causally significant for the output, as assessed by Granger causality. Because our approach requ...
Article
The brain-derived neurotrophic factor (BDNF) plays an important role in neuronal development, and in the formation and plasticity of synaptic connections. These effects of BDNF are at least partially due to the ability of the neurotrophin to increase protein synthesis both globally and locally. However, only a few proteins have been shown to be up-...
Article
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Recent recordings of place field activity in rodent hippocampus have revealed correlates of current, recent past, and imminent future events in spatial memory tasks. To analyze these properties, we used a brain-based device, Darwin XI, that incorporated a detailed model of medial temporal structures shaped by experience-dependent synaptic activity....
Article
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Eukaryotic mRNAs often recruit ribosomal subunits some distance upstream of the initiation codon; however, the mechanisms by which they reach the initiation codon remain to be fully elucidated. Although scanning is a widely accepted model, evidence for alternative mechanisms has accumulated. We previously suggested that this process may involve tet...
Article
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We studied whether magnetoencephalography (MEG) could detect deceptive responses on a single-subject, trial-by-trial basis. To elicit spontaneous, ecologically valid deception, we developed a paradigm in which subjects in a simulated customs setting were presented with a series of pictures of items which might be in their baggage, and for each item...
Article
A recent theoretical emphasis on complex interactions within neural systems underlying consciousness has been accompanied by proposals for the quantitative characterization of these interactions. In this article, we distinguish key aspects of consciousness that are amenable to quantitative measurement from those that are not. We carry out a formal...
Article
The paper considers a Darwinian approach to the traditional mind-body problem and the problem of consciousness, called ‘neural Darwinism’. It describes essential features of consciousness and brain structures, putting strong emphasis not just on the action of brain regions but also on their interaction. The theory of neural Darwinism describes the...
Article
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In eukaryotes, 40S ribosomal subunits move from their recruitment site on the mRNA to the initiation codon by an as yet poorly understood process. One postulated mechanism involves ribosomal shunting, in which ribosomal subunits completely bypass regions of the 5′ leader. For some mRNAs, shunting has been shown to require various mRNA elements, som...
Article
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The cerebellum is known to be critical for accurate adaptive control and motor learning. We propose here a mechanism by which the cerebellum may replace reflex control with predictive control. This mechanism is embedded in a learning rule (the delayed eligibility trace rule) in which synapses onto a Purkinje cell or onto a cell in the deep cerebell...
Article
The following article is reprinted here in lieu of Gerald Edelman's remarks at the symposium; it covers virtually all the material that he presented in his address, which was titled, “Darwinian Competition Among Neurons.” The article is reprinted by permission of Daedalus, Journal of the Academy of Arts and Sciences, from the issue entitled “The Br...
Article
A new RoboCup soccer league is being developed, focussing on human-robot interaction. In this league each team consists of both human players, mounted on Segway HT scooters, and a robotic version of the Segway; both human and robot players must cooperate to score goals. This paper presents details of the physical design of our autonomous Segway Soc...
Article
Without a doubt the most sophisticated behaviour seen in biological agents is demonstrated by or-ganisms whose behaviour is guided by a nervous system. Thus, the construction of behaving de-vices based on principles of nervous systems may have much to offer. Our group has built series of brain-based devices (BBDs) over the last 14 years to provide...
Book
Burgeoning advancements in brain science are opening up new perspectives on how we acquire knowledge. Indeed, it is now possible to explore consciousness--the very center of human concern--by scientific means. In this illuminating book, Dr. Gerald M. Edelman offers a new theory of knowledge based on striking scientific findings about how the brain...
Article
The simultaneous study of brain function at all levels of organization is difficult to undertake with current experimental tools. Present day electrophysiology only allows the recording of at most hundreds of neurons while an animal is performing a behavioral task. Because of this limitation and the sheer complexity of the nervous system, computati...
Article
Fragile X syndrome (FXS) is caused by the transcriptional silencing of the Fmr1 gene, which encodes a protein (FMRP) that can act as a translational suppressor in dendrites, and is characterized by a preponderance of abnormally long, thin and tortuous dendritic spines. According to a current theory of FXS, the loss of FMRP expression leads to an ex...
Article
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In earlier studies, we identified short (6- to 22-nt) sequences that functioned as internal ribosome entry sites (IRESes) and enhanced translation. The size of these IRES elements suggested that they might be prevalent within the messenger population and that individual elements might affect the translation of different groups of mRNAs. To begin to...
Article
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The expression of Rbm3, a glycine-rich RNA-binding protein, is enhanced under conditions of mild hypothermia, and Rbm3 has been postulated to facilitate protein synthesis at colder temperatures. To investigate this possibility, Rbm3 was overexpressed as a c-Myc fusion protein in mouse neuroblastoma N2a cells. Cells expressing this fusion protein sh...
Article
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Analyzing neural dynamics underlying complex behavior is a major challenge in systems neurobiology. To meet this challenge through computational neuroscience, we have constructed a brain-based device (Darwin X) that interacts with a real environment, and whose behavior is guided by a simulated nervous system incorporating detailed aspects of the an...
Article
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Fragile X syndrome results from the transcriptional silencing of a gene, Fmr1, that codes for an mRNA-binding protein (fragile X mental retardation protein, FMRP) present in neuronal dendrites. FMRP can act as a translational suppressor, and its own translation in dendrites is regulated by group I metabotropic glutamate receptors (mGluRs). Multiple...
Article
We describe Darwin X, a physical device that interacts with a real environment, whose behavior is guided by a simulated nervous system incorporating aspects of the detailed anatomy and physiology of the hippocampus and its surrounding regions. This brain-based device integrates cues from its environment and solves a spatial memory task. The respons...
Article
Effective visual object recognition requires mechanisms to bind object features (e.g. color, shape and motion) while distinguishing distinct objects. Synchronously active neuronal circuits among reentrantly connected cortical areas may provide a basis for visual binding. To assess the potential of this mechanism, we have constructed a mobile brain-...
Article
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The mechanism by which the neural cell adhesion molecule, N-CAM, mediates homophilic interactions between cells has been variously attributed to an isologous interaction of the third immunoglobulin (Ig) domain, to reciprocal binding of the two N-terminal Ig domains, or to reciprocal interactions of all five Ig domains. Here, we have used a panel of...
Article
The complete amino acid sequence of a human gammaG1 immunoglobulin (Eu) has been determined and the arrangement of all of the disulfide bonds has been established. Comparison of the sequence with that of another myeloma protein (He) suggests that the variable regions of heavy and light chains are homologous and similar in length. The constant porti...
Article
A neuronal network inspired by the anatomy of the cerebral cortex was simulated to study the self-organization of spiking neurons into neuronal groups. The network consisted of 100 000 reentrantly interconnected neurons exhibiting known types of cortical firing patterns, receptor kinetics, short-term plasticity and long-term spike-timing-dependent...
Article
Sleep is a ubiquitous component of animal life, and prolonged sleep deprivation is fatal in both vertebrates and invertebrates. The physiologic function of sleep, however, is not known. We propose here that sleep provides a period of time necessary to reapportion resources within neurons and neural systems that become sub-optimally distributed duri...
Chapter
The mammalian brain is an extraordinary object: its networks give rise to our conscious experiences as well as to the generation of adaptive behavior for the organism within its environment. Progress in understanding the structure, dynamics and function of the brain faces many challenges. Biological neural networks change over time, their detailed...
Article
The noradrenergic locus coeruleus (LC) has been implicated in the promotion of arousal, in focused attention and learning, and in the regulation of the sleep/waking cycle. The complex biological functions of the central noradrenergic system have been investigated largely through electrophysiological recordings and neurotoxic lesions of LC neurons....
Article
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We previously reported that the 5' leader of the mRNA-encoding initiation factor eIF4G in Saccharomyces cerevisiae can function as a translational enhancer and as an internal ribosome entry site (IRES) when tested in cells. However, Verge and colleagues recently suggested that this sequence does not facilitate translation initiation, but inhibits t...
Article
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We previously identified an internal ribosome entry site (IRES) within the 5' leader of the mRNA encoding the Gtx homeodomain protein and showed that shorter nonoverlapping segments of this 5' leader could enhance the translation of a second cistron in a dicistronic mRNA. One of these segments was 9 nt in length, and when multiple copies of this IR...
Article
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beta-Secretase [also known as the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1)] is an enzyme involved in the production of A beta-amyloid plaques in the brains of patients with Alzheimer's disease. The enhanced production of this enzyme occurs without corresponding changes in BACE1 mRNA levels. The complex 5' leader of BACE1 mRNA c...
Article
How does environmental structure influence the dynamics of adaptive behavior and its underlying mechanisms? By analyzing the neural controller of a simulated head/eye system, we show that a specific measure—“neural complexity”—can be selectively sensitive to neural dynamics underlying rich adaptive behavior. Evolutionary algorithms were used to gen...
Conference Paper
Whiskers are widely used by many animal species for navigation and texture discrimination. This paper describes Darwin IX, a mobile physical device equipped with artificial whiskers, the behavior of which is controlled by a neural simulation based on the rat somatosensory system. During its autonomous behavior, Darwin IX is able to discriminate amo...
Article
In many cell types, translation can be regulated by a redistribution of translation initiation factors to actin-based cytoskeletal compartments that contain bound mRNAs. This process is evoked by extracellular signals and is regulated by determinants of cytoskeletal organization, such as integrins. In the present experiments, we provide evidence th...
Article
By constructing and analyzing a physically situated brain-based device (i.e. a device with sensors and actuators whose behavior is guided by a simulated nervous system), we show that reentrant connectivity and dynamic synchronization can provide an e#ective mechanism for binding the visual features of objects.
Article
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In previous studies, we demonstrated the sufficiency of short nucleotide sequences to facilitate internal initiation of translation in mammalian cells. By using a selection methodology, we have now identified comparable sequences in Saccharomyces cerevisiae. For these studies, a library of constructs expressing dicistronic mRNAs with the HIS3 gene...
Article
Consciousness has a number of apparently disparate properties, some of which seem to be highly complex and even inaccessible to outside observation. To place these properties within a biological framework requires a theory based on a set of evolutionary and developmental principles. This paper describes such a theory, which aims to provide a unifyi...
Article
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This paper presents evidence indicating that the signals generated by neural responses to visual input can be either enhanced by increasing or suppressed by decreasing the area of the stimuli to which attention is directed. We used magnetoencephalography (MEG) to measure the frequency-tagged steady-state visual evoked responses of 11 subjects prese...
Article
By constructing and analyzing a physically situated brain-based device (i.e. a device with sensors and actuators whose behavior is guided by a simulated nervous system), we show that reentrant connectivity and dynamic synchronization can provide an effective mechanism for binding the visual features of objects.
Article
Full-text available
A variety of posttranscriptional mechanisms affects the processing, subcellular localization, and translation of messenger RNAs (mRNAs). Translational control appears to occur primarily at the initiation rather than the elongation stage. It has been suggested that translation is mediated largely by means of a cap-binding/scanning mechanism. On the...
Article
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In studying brain activity during the behavior of living animals, it is not possible simultaneously to analyze all levels of control from molecular events to motor responses. To provide insights into how levels of control interact, we have carried out synthetic neural modeling using a brain-based real-world device. We describe here the design and p...
Article
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We previously demonstrated that the neural cell adhesion molecule (N-CAM) inhibited the proliferation of cultured rat hippocampal progenitor cells and increased the number of neurons generated. We demonstrate here that the continued presence of fibroblast growth factor 2 along with N-CAM or brain-derived neurotrophic factor over 12 days of culture...
Article
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Protein synthesis in neurons is essential for the consolidation of memory and for the stabilization of activity-dependent forms of synaptic plasticity such as long-term potentiation (LTP). Activity-dependent translation of dendritically localized mRNAs has been proposed to be a critical source of new proteins necessary for synaptic change. mRNA for...
Article
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Changes in the morphology of dendritic spines are correlated with synaptic plasticity and may relate mechanistically to its expression and stabilization. Recent work has shown that spine length can be altered by manipulations that affect intracellular calcium, and spine length is abnormal in genetic conditions affecting protein synthesis in neurons...
Article
To identify molecular interaction partners of the cellular prion protein (PrPC), we sought to apply an in situ crosslinking method that maintains the microenvironment of PrPC. Mild formaldehyde crosslinking of mouse neuroblastoma cells (N2a) that are susceptible to prion infection revealed the presence of PrPC in high molecular mass (HMM) protein c...
Article
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Degeneracy, the ability of elements that are structurally different to perform the same function or yield the same output, is a well known characteristic of the genetic code and immune systems. Here, we point out that degeneracy is a ubiquitous biological property and argue that it is a feature of complexity at genetic, cellular, system, and popula...
Article
Homophilic binding of the neural cell adhesion molecule (N-CAM) mediates the calcium-independent cell-cell adhesion that is involved in neuronal development. Two hypotheses have been advanced for the mechanism of homophilic binding. Cell-based experiments have implicated each of the five extracellular immunoglobulin (Ig) domains of N-CAM in the hom...
Article
This chapter summarizes a theory of consciousness based on brain structure and dynamics. The theory centers around the notion of reentry—ongoing recursive signaling across multiple reciprocally connected brain regions present mainly in the thalamocortical system. It recognized the fundamental beginnings provided by the complementary efforts of Ramo...
Article
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In neurons, translation of dendritically localized mRNAs is thought to play a role in affecting synaptic efficacy. Inasmuch as components of the translation machinery may be limiting in dendrites, we investigated the mechanisms by which translation of five dendritically localized mRNAs is initiated. The 5' leader sequences of mRNAs encoding the act...