No overarching hypotheses tie the basic mechanisms of mitochondrial reactive oxygen species (ROS) production to activity dependent synapse pruning—a fundamental biological process in health and disease. Neuronal activity divergently regulates mitochondrial ROS: activity decreases whereas inactivity increases their production, respectively. Placing mitochondrial ROS as innate synaptic activity sentinels informs the novel hypothesis that: (1) at an inactive synapse, increased mitochondrial ROS production initiates intrinsic apoptosis dependent pruning; and (2) at an active synapse, decreased mitochondrial ROS (...) production masks intrinsic apoptosis dependent pruning. Immature antioxidant defense may enable the developing brain to harness mitochondrial ROS to prune weak synapses. Beyond development, endogenous antioxidant defense constrains mitochondrial (ROS) to mask pruning. Unwanted age‐related synapse loss may arise when mitochondrial ROS aberrantly recapitulate developmental pruning. Placing mitochondrial ROS with their hands on the shears is beneficial in early but deleterious in later life. (shrink)

In this paper I propose a hypothetical model of mental causation that I call semantic pruning and which could be defined as the causal influence of contents and meanings on the spatial configuration of the network of synapses of an individual. I will be guided by two central principles: 1) the causal influence of the mental occurs by virtue of external semantic constraints and consists in the selective activation of certain physical powers, 2) when the selective activation is continual, (...) it triggers a process of synaptic pruning in the neural and neuromuscular network. (shrink)

We propose that the primary cause of schizophrenia is a pathological extension of synaptic pruning involving local connectivity that unfolds ordinarily during adolescence. Computer simulations suggest that this pathology provides reasonable accounts of a range of symptoms in schizophrenia, and is consistent with recent postmortem and genetic studies. NMDA-receptors play a regulatory role in maintaining and/or eliminating cortical synapses, and therefore may play a pathophysiological role.

A model of an intentional self-observing system is proposed based on the structure and functions of astrocyte-synapse interactions in tripartite synapses. Astrocyte-synapse interactions are cyclically organized and operate via feedforward and feedback mechanisms, formally described by proemial counting. Synaptic, extrasynaptic and astrocyte receptors are interpreted as places with the same or different quality of information processing described by the combinatorics of tritograms. It is hypothesized that receptors on the astrocytic membrane may embody intentional programs that select corresponding synaptic (...) and extrasynaptic receptors for the formation of receptor-receptor complexes. Basically, the act of self-observation is generated if the actual environmental information is appropriate to the intended observation processed by receptor-receptor complexes. This mechanism is implemented for a robot brain enabling the robot to experience environmental information as “its own”. It is suggested that this mechanism enables the robot to generate matches and mismatches between intended observations and the observations in the environment, based on the cyclic organization of the mechanism. In exploring an unknown environment the robot may stepwise construct an observation space, stored in memory, commanded and controlled by the intentional self-observing system. Finally, the role of self-observation in machine consciousness is shortly discussed. (shrink)

. Progress in technology has allowed dynamic research on the development of the human brain that has revolutionized concepts. Particularly, the notions of plasticity, neuronal selection, and the effects of afferent stimuli have entered into thinking about brain development. Here I focus on development from the age of four years to early adulthood, during which a 30 percent reduction in some brain synapses occurs that is out of proportion to changes in neuronal numbers. This corresponds temporally with changes in normal (...) child behavior from the loose‐associative, almost schizoid, thinking and art of the four‐year‐old to the more trained, or disciplined, or acculturated—and restrained—personality of the young adult. I propose that the synaptic changes can best be thought of as a winnowing process likely subject to environmental influences. Acquisition of language and the ability to link linguistic cognition to the plastic development of the brain provide a potentially powerful means of explaining the evolutionally explosive development of human cognition and culture. Schizophrenia, a disease that can be envisioned as representing a derangement of synaptic maturation, may provide an entry into the search for genes controlling the processes mediating the unprecedented development of Homo sapiens over the past 40,000 to 70,000 years. The recently completed mapping of the genome of the chimpanzee provides a new frame of reference that may speed the search. (shrink)

Phillips & Silverstein emphasize the gain-control properties of NMDA synapses in cognitive coordination. We endorse their view and suggest that NMDA synapses play a crucial role in biased attentional competition and (visual) working memory. Our simulations show that NMDA synapses can control the storage rate of visual objects. We discuss specific predictions of our model about cognitive effects of NMDA-antagonists and schizophrenia.

argue that natural selection does not explain the genotypic arid phenotypic properties of individuals. On this view, natural selection explains the adaptedness of individuals, not by explaining why the individuals that exist have the adaptations they do, but rather by explaining why the individuals that exist are the ones with those adaptations. This paper argues that this ‘Negative’ view of natural selection ignores the fact that natural selection is a cumulative selection process. So understood, it explains how the genetic sequences (...) that individuals inherit and that are responsible for their complex (and co-adapted) adaptations first arose in the gene-pool. (shrink)

This selective review explores biologically inspired learning as a model for intelligent robot control and sensing technology on the basis of specific examples. Hebbian synaptic learning is discussed as a functionally relevant model for machine learning and intelligence, as explained on the basis of examples from the highly plastic biological neural networks of invertebrates and vertebrates. Its potential for adaptive learning and control without supervision, the generation of functional complexity, and control architectures based on self-organization is brought forward. Learning without (...) prior knowledge based on excitatory and inhibitory neural mechanisms accounts for the process through which survival-relevant or task-relevant representations are either reinforced or suppressed. The basic mechanisms of unsupervised biological learning drive synaptic plasticity and adaptation for behavioral success in living brains with different levels of complexity. The insights collected here point toward the Hebbian model as a choice solution for “intelligent” robotics and sensor systems. Keywords: Hebbian learning; synaptic plasticity; neural networks; self-organization; brain; reinforcement; sensory processing; robot control . (shrink)

The self, Joseph LeDoux tells us, is “the totality of the living organism”. Most disciplines in the natural sciences focus on only one or two levels of organization. Indeed, Dmitri Mendeleev figured out the periodic table of the elements without knowing any of the underlying quantum mechanics or stereochemistry. There are, however, at least a dozen levels of organization within the neurosciences — and, if we use a metaphor, we temporarily create yet another. This leads to considerable confusion and arguments (...) at cross purposes over whether learning is an alteration at the level of gene expression, ion channels, synapses, neurons or circuits. Each neuron has thousands of synapses, which produce currents that summate to form an impulse train. But only rarely is the activity of a single neuron sufficient to cause a perception or trigger an action. Neurons usually act as members of ‘committees’ — what Donald Hebb in 1949 called cellassemblies. Just as in academia, one individual may function in different committees on different occasions. A concept, including any explicit memory that we can talk about, is probably formed by such a committee. Implicit memories are less differentiated — they are part of the ‘feltwork’, together with motivations and emotions, that biases the choice of one’s next act. In this well-written 400-page appreciation of behavioural neuroscience, LeDoux argues that synapses are the seat of self. He says, in effect, that you are your memories; that it is the uniqueness of an array of synaptic strengths that distinguishes one twin from another. Fair enough, but why not instead focus on one’s unique array of ion channels? Or neurons, because a neuron is the closest thing we have to a computational unit? Or one’s unique arrangement of those overlapping, redundant hebbian committees? None of these make for a catchy book title, but relating other things to the synapses proves to be a good way of covering a lot of fascinating material at the overlying levels, including a few updates to LeDoux’s earlier book The Emotional Brain. (shrink)

Alpha-beta pruning is a technique for pruning trees in artificial intelligence game-playing. This note draws an analogy between the technique, which is, in essence, an application of many-valued logic to the cut-off of the evaluation of conditionals in computer programs (for efficiency).

Recent studies suggest that the tetracycline antibiotic minocycline, or its cousins, hold therapeutic potential for affective and psychotic disorders. This is proposed on the basis of a direct effect on microglia‐mediated frontocortical synaptic pruning (FSP) during adolescence, perhaps in genetically susceptible individuals harboring risk alleles in the complement component cascade that is involved in this normal process of CNS circuit refinement. In reviewing this field, it is argued that minocycline is actually probing and modulating a deeply evolved and intricate (...) system wherein psychosocial stimuli sculpt the circuitry of the “social brain” underlying adult behavior and personality. Furthermore, this system can generate psychiatric morbidity that is not dependent on genetic variation. This view has important ramifications for understanding “pathologies” of human social behavior and cognition as well as providing long‐sought potential mechanistic links between social experience and susceptibility to mental and physical disease. (shrink)

The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Non-bilaterian metazoans, both with and without neurons and their closest relatives already contain many components of the molecular toolkits for synapse functions. The origin of these components and their assembly into ancient synaptic signaling machineries are particularly important in light of recent findings on the phylogeny of non-bilaterian metazoans. The evolution of synapses and neurons are often discussed only from a metazoan perspective leaving a (...) considerable gap in our understanding. By taking an integrative approach we highlight the need to consider different, but extremely relevant phyla and to include the closest unicellular relatives of metazoans, the ichthyosporeans, filastereans and choanoflagellates, to fully understand the evolutionary origin of synapses and neurons. This approach allows for a detailed understanding of when and how the first pre- and postsynaptic signaling machineries evolved. The evolutionary origin of synapses and neurons is an enigmatic subject that inspires much debate. Most of our knowledge and recent discussions are biased towards a metazoan perspective, leaving a considerable gap in our understanding. Recent work has now revealed important insights into the emergence and co-regulation of complex synaptic signaling machineries from studies in the closest unicellular relatives of metazoans. (shrink)

A dualistic approach to consciousness is presented that employs Hebbian synaptic dynamics and the basic notion of measurement in science to bridge the so-called explanatory gap between first-person consciousness and third-person science. Unconscious processing by neural circuitry characterizes (i) the neuron as a measuring instrument and (ii) the neural signal as the quantity to be measured. Hebbian synaptic dynamics, effectuating the storage of information, implements the role of an observer of a measurement outcome. The approach extends physical renormalization techniques, as (...) applied to phase changes, to biology. This leads to the proposal of a ramification process in neural systems (brains) from a primitive form of sensation associated with the Hebbian synapse toward more elaborate experiential forms of consciousness (feelings, qualia) associated with hierarchies of neuronal assemblies. Characterizing sensation as a form of mutual information at the synaptic level motivates a relation between consciousness and phase changes of information. (shrink)

In this paper we present the problem of a noisy lexical taxonomy and suggest two tasks as potential remedies. The first task is to identify and eliminate incorrect hypernymy links, and the second is to repopulate the taxonomy with new relations. The first task consists of revising the entire taxonomy and returning a Boolean for each assertion of hypernymy between two nouns (e.g. brie is a kind of cheese). The second task consists of recursively producing a chain of hypernyms for (...) a given noun, until the most general node in the taxonomy is reached (e.g. brie → cheese → food → etc.). In order to achieve these goals, we implemented a hybrid hypernym-detection algorithm that incorporates various intuitions, such as syntagmatic, paradigmatic and morphological association measures as well as lexical patterns. We evaluate these algorithms individually and collectively and report findings in Spanish, English and French. (shrink)

The developing neuromuscular junction has provided an important paradigm for studying synapse formation. An outstanding feature of neuromuscular differentiation is the aggregation of acetylcholine receptors (AChRs) at high density in the postsynaptic membrane. While AChR aggregation is generally believed to be induced by the nerve, the mechanisms underlying aggregation remain to be clarified. A 43‐kD protein (43k) normally associated with the cytoplasmic aspect of AChR clusters has long been suspected of immobilizing AChRs by linking them to the cytoskeleton. In (...) recent studies, the AChR clustering activity of 43k has, at last, been demonstrated by expressing recombinant AChR and 43k in non‐muscle cells. Mutagenesis of 43k has revealed distinct domains within the primary structure which may be responsible for plasma membrane targeting and AChR binding. Other lines of study have provided clues as to how nerve‐derived (extracellular) AChR‐cluster inducing factors such as agrin might activate 43k‐driven postsynaptic membrane specialization. (shrink)

Athenian ostracism has long captured democratic imaginations because it seems to present clear evidence of a people (demos) routinely asserting collective power over tyrannical elites. In recent times, ostracism has been particularly alluring to militant democrats, who see the institution as an ancient precursor to modern militant democratic mechanisms such as social media bans, impeachment measures, and lustration procedures, which serve to protect democratic constitutions from anti-democratic threats. Such a way of conceptualizing ostracism ultimately stems from Aristotle’s “rule of proportion,” (...) or the removal of “outstanding” individuals in a polity who threaten to disturb the achievement of communal eudaimonia (Aris. Pol. 1284a). However, this way of interpreting the institution only presents a truncated view, one which is overly centered on the ultimate expulsion of an individual from the polity, rather than on its broader contextual telos—the transformation of the ostracized individual and of the community. To move past this simplified view, this paper considers all elements of ostracism with equal force, and argues that ostracism offered a shared opportunity and shared space for all members of the polis—citizens, non-citizens, and elite members alike—to reform the character of the subject individual and to instill and reaffirm democratic values in the community. (shrink)

We recently described a novel form of stress‐associated bidirectional plasticity at GABA synapses onto hypothalamic parvocellular neuroendocrine cells (PNCs), the apex of the hypothalamus‐pituitary‐adrenal axis. This plasticity may contribute to neuroendocrine adaptation. However, this GABA synapse plasticity likely does not translate into a simple more and less of inhibition because the ionic driving force for Cl−, the primary charge carrier for GABAA receptors, is dynamic. Specifically, stress impairs a Cl− extrusion mechanism in PNCs. This not only renders the steady‐state (...) GABA response less hyperpolarizing but also makes PNCs susceptible to the activity‐dependent accumulation of Cl−. Accordingly, GABA synapse plasticity impacts both the robustness of GABA voltage response and dynamic Cl− loading, imposing nonlinear influences on PNC excitability during circuit activities. This theoretical consideration predicts roles for GABA transmission far more versatile than canonical inhibition. We propose potential impacts of GABA synapse plasticity on the experience‐dependent fine‐tuning of neuroendocrine stress responses. (shrink)

There are remarkable behavioral, neural, and genetic similarities between the way songbirds learn to sing and human infants learn to speak. Furthermore, the brain regions involved in birdsong learning, perception, and production have been identified and characterized in detail. In particular, the caudal medial nidopallium (the avian analog of the mammalian auditory‐association cortex) has been found to contain the neural substrate of auditory memory, paving the way for analyses of the underlying molecular mechanisms. Recently, the zebra finch genome was sequenced, (...) and annotated cDNA databases representing over 15,000 unique brain‐expressed genes are available, enabling high‐throughput gene expression analyses. Here we review the involvement of immediate early genes (e.g. zenk and arc), their downstream targets (e.g. synapsins), and their regulatory signaling pathways (e.g. MAPK/ERK) in songbird memory. We propose that in‐depth investigations of zenk‐ and ERK‐dependent cascades will help to further unravel the molecular basis of auditory memory. (shrink)

A formalism is introduced to represent the connective organization of an evolving neuronal network and the effects of environment on this organization by stabilization or degeneration of labile synapses associated with functioning. Learning, or the acquisition of an associative property, is related to a characteristic variability of the connective organization: the interaction of the environment with the genetic program is printed as a particular pattern of such organization through neuronal functioning. An application of the theory to the development of the (...) neuromuscular junction is proposed and the basic selective aspect of learning emphasized. (shrink)

Discussions of branching time and branching spacetime have become common in the philosophical literature. If properly understood, these conceptions can be harmless. But they are sometimes used in the service of debatable and even downright pernicious doctrines. The purpose of this chapter is to identify the pernicious branching and prune it back.

I wholeheartedly endorse Grodzinsky's program of attempting to tie the particular deficits observed in Broca's aphasics' comprehension and production to changes in their mentally represented model of grammar. At the level of detail, however, I see problems with two specific changes that Grodzinsky posits. One is a default Agent-assignment strategy in comprehension. The other is the hypothesis that production involves pruning all functional projections above Agreement Phrase.

Good Agricultural Practices are central to sustainability standards and certification programmes in the global cocoa chain. Pruning is one of the practices promoted in extension services associated with these sustainability efforts. Yet concerns exist about the low adoption rate of these GAPs by smallholder cocoa farmers in Ghana. A common approach to addressing this challenge is based on creating enabling conditions and offering appropriate incentives. We use the concepts of inscription and affordance to trace the vertically coordinated travel of (...) recommended pruning from research to extension and farming sites, and to describe how pruning is carried out differently at each site. Our analysis suggests that enactments of pruning at the extension site reduce the number of options and space for interactions, and this constrains making the practice meaningful to farmers’ repertoires. The conventions guiding and legitimising actions at this site, reinforced by sustainability standards, certification schemes and associated inspections and audits, favour standardised recommendations and consequently narrow room for context-specific diagnostics and adaptions. Therefore, we reframe the adoption problem as a matter of fit between different sites in the ‘agricultural research value chain’ embedded in the operational cocoa chain. Our contribution problematises the dominant framing of low adoption and highlights that the movement of pruning and the sequential enactment at different sites constrain the affordances available for rendering the practice meaningful to farmers’ repertoires. Consequently, addressing the low uptake of GAPs requires institutional work towards conventions that can construct a fit between sites along the agricultural research value chain. (shrink)

Tree branches near the electric power transmission lines are of great threat to the electricity supply. Nowadays, the tasks of clearing threatening tree branches are still mostly operated by hand and simple tools. Traditional structures of the multirotor aerial robot have the problem of fixed structure and limited performance, which affects the stability and efficiency of pruning operation. In this article, in order to obtain better environmental adaptability, an active deformable trees-pruning aerial robot is presented. The deformation of (...) the aerial robot is implemented through two ways, arm telescopic and folding. In order to suppress the influence of internal and external disturbances on the system, Active Disturbance Rejection Control technology is adopted to build the flight controller. Firstly, active deformation aerial robot structure is given, followed by system dynamic model establishment under wind disturbance using the Newton–Euler method. Also, the analysis of the gusts influence on the system is considered. Then, the active deformation aerial robot system is decoupled into a combination of six SISO systems, so that a disturbance rejection controller is designed. Finally, the expanded state observer and the nonlinear state error feedback law are used to inspect and compensate the disturbance. Simulation results of attitude and position tracking as well as the antidisturbance capability show that the active deformation aerial robot with the ADRC flight controller designed in this paper has excellent attitude control capabilities during flight and trees-pruning operation. (shrink)

Recent experiments have begun to decipher the molecular dialog that mediates differentiation at sites of synaptic between neurons and their targets. It had been hypothesized that the protein agrin is released by axon terminals at embryonic neuromuscular junctions and binds to a receptor on the myofiber surface to trigger postsynaptic differentiation. Now a genetic ‘Knockout’ experiment has confirmed the essential role of agrin in signaling between developing nerve and muscle(1). A second ‘knockout’ has shown that the muscle‐specific receptor tyrosine kinase (...) MuSK is a critical element in the agrin‐induced signaling cascade(2). Additional results suggest that MuSK may comprise a portion of the agrin receptor(3). (shrink)

I begin with a characterization of neurolinguistic theories, trying to pinpoint some general properties that an account of brain/language relations should have. I then address specific criticisms made in the commentaries regarding the syntactic theory assumed in the target article, properties of the Trace Deletion Hypothesis (TDH) and the Tree-Pruning Hyothesis (TPH), other experimental results from aphasia, and findings from functional neuroimaging. Despite the criticism, the picture of the limited role of Broca's area remains unchanged.

Neuromuscular synapses are highly dynamic structures that respond to both intercellular and intracellular cues to manipulate synaptic form. A variety of post‐translational modifications of synaptic proteins are used to regulate synaptic plasticity. A recent report by DiAntonio et al.(1) shows that two ubiquitin pathway proteins, Highwire and Fat facets, may be mutually antagonistic regulators of presynaptic growth at the Drosophila neuromuscular junction. This work adds support to the emerging idea that ubiquitin, a polypeptide that targets proteins for proteasomal degradation, regulates (...) synaptic development. BioEssays 24:13–16, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

The English Court of Appeal is currently faced with three analytically distinct approaches to the question of when one party owes another a duty of care in respect of her economic interests, all of which bear the authority of the House of Lords. Unable to choose between them, it has recently adopted a fourth approach combining which combines them, in the apparent belief that the combination will eradicate any individual deficiencies. Against the background of a recent case, the author argues (...) that this is a holding strategy at best and methodologically deficient. He also challenges the continuing lip-service paid by courts to models of liability based upon ‘assumptions of responsibility,’ examining and criticising the causes of their persistence in the law in the face of widespread academic criticism. Instead, the author argues, the House of Lords should now clearly endorse a single reasoning strategy to economic loss cases based on the three-stage approach in Caparo Industries v Dickman. Properly understood, this approach offers the best prospect of facilitating consistent and transparent decision-making in the longer term. (shrink)

The ubiquitin proteasome system is a potent regulatory mechanism used to control protein stability in numerous cellular processes, including neural development. Many neurodegenerative diseases are featured by the accumulation of UPS‐associated proteins, suggesting the UPS dysfunction may be crucial for pathogenesis. Recent experiments have highlighted the UPS as a key player during synaptic development. Here we summarize recent discoveries centered on the role of the UPS in synapse remodeling and draw attention to the potential link between the synaptic UPS (...) dysfunction and the pathology of neurodegenerative diseases. BioEssays 30:1075–1083, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

How do human infants learn the causal dependencies between events? Evidence suggests that this remarkable feat can be achieved by observation of only a handful of examples. Many computational models have been produced to explain how infants perform causal inference without explicit teaching about statistics or the scientific method. Here, we propose a spiking neuronal network implementation that can be entrained to form a dynamical model of the temporal and causal relationships between events that it observes. The network uses spike-time (...) dependent plasticity, long-term depression, and heterosynaptic competition rules to implement Rescorla–Wagner-like learning. Transmission delays between neurons allow the network to learn a forward model of the temporal relationships between events. Within this framework, biologically realistic synaptic plasticity rules account for well-known behavioral data regarding cognitive causal assumptions such as backwards blocking and screening-off. These models can then be run as emulators for state inference. Furthermore, this mechanism is capable of copying synaptic connectivity patterns between neuronal networks by observing the spontaneous spike activity from the neuronal circuit that is to be copied, and it thereby provides a powerful method for transmission of circuit functionality between brain regions. (shrink)