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)

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)

. 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.

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

During late embryonic and early postnatal development, synaptic connections are extensively modified so that some functional connections are weakened and eliminated from a neural circuit while others are strengthened and maintained. The mechanisms that underlie synapse elimination are beginning to be understood from studies of the neuromuscular junction. A recent paper(1) provides some intriguing insights into the role proteases may play in the developmental disassembly of neuromuscular synapses.

SNAREs (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors) are a large family of proteins that are present on all organelles involved in intracellular vesicle trafficking and secretion. The interaction of complementary SNAREs found on opposing membranes presents an attractive lock‐and‐key mechanism, which may underlie the specificity of vesicle trafficking. Moreover, formation of the tight complex between a vesicle membrane SNARE and corresponding target membrane SNAREs could drive membrane fusion. In synapses, this tight complex, also referred to as the synaptic core complex, (...) is essential for neurotransmitter release. However, recent observations in knockout mice lacking major synaptic SNAREs challenge the prevailing notion on the executive role of these proteins in fusion and open up several questions about their exact role(s) in neurotransmitter release. Persistence of a form of regulated neurotransmitter release in these mutant mice also raises the possibility that other cognate or non‐cognate SNAREs may partially compensate for the loss of a particular SNARE. Future analysis of SNARE function in central synapses will also have implications for the role of these molecules in other vesicle trafficking events such as endocytosis and vesicle replenishment. Such analysis can provide a molecular basis for synaptic processes including certain forms of short‐term synaptic plasticity. BioEssays 24:926–936, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Vadim Fedulov,1 Christopher S. Rex,2 Danielle A. Simmons,3 Linda Palmer,4 Christine M. Gall,1,2 and Gary Lynch.

CALHM1 was recently demonstrated to be a voltage‐gated ATP‐permeable ion channel and to serve as a bona fide conduit for ATP release from sweet‐, umami‐, and bitter‐sensing type II taste cells. Calhm1 is expressed in taste buds exclusively in type II cells and its product has structural and functional similarities with connexins and pannexins, two families of channel protein candidates for ATP release by type II cells. Calhm1 knockout in mice leads to loss of perception of sweet, umami, and bitter (...) compounds and to impaired gustatory nerve responses to these tastants. These new studies validate the concept of ATP as the primary neurotransmitter from type II cells to gustatory neurons. Furthermore, they identify voltage‐gated ATP release through CALHM1 as an essential molecular mechanism of ATP release in taste buds. We discuss these new findings, as well as unresolved issues in peripheral taste signaling that we hope will stimulate future research. (shrink)

Recently a number of complex electrophysiological responses to neurotransmitters have been observed that cannot be described as simple excitation or inhibition. These responses are often characterized as modulatory, although there is no consensus on what defines modulation. Morphological studies reveal certain neurotransmitters stored in what might be release sites without synaptic contact. There is no direct evidence for nonsynaptic release from CNS sites, although such release does occur in the periphery and in invertebrates. Nonsynaptic release might provide a basis for (...) diffuse one-cell-to-many communication, but it might also simply be a means of sending the transmitter to a broader area of a single neuron than occurs in typical synapses. Several kinds of macromolecules have been found to be transported in a retrograde direction – and in some cases transsynaptically. There have been suggestions that some neurons may release more than one type of transmitter. Particularly intriguing is the possibility of release of substances that modulate actions of a primary transmitter. Taken together this range of evidence suggests that neurons may use a variety of forms of molecular communication in addition to traditionally described synaptic transmission.Several authors have suggested modes of communication distinct from classical synaptic transmission and have classified released substances using terms such as neurohumor, neurohormone, neuroregulator, and modulator. These suggestions have the heuristic value of drawing together diverse kinds of data, but it remains to be established that the pieces fit together in that fashion – for example, that complex electrophysiological effects are associated with substances released nonsynaptically. In order to reduce confusion, a flexible, generic approach to nomenclature for substances released from neurons and for hypothetical modes of communication is recommended. Some behavioral implications of nonconventional transmission are considered. (shrink)

Capacity of conscious agents to perform genuine choices among future alternatives is a prerequisite for moral responsibility. Determinism that pervades classical physics, however, forbids free will, undermines the foundations of ethics, and precludes meaningful quantification of personal biases. To resolve that impasse, we utilize the characteristic indeterminism of quantum physics and derive a quantitative measure for the amount of free will manifested by the brain cortical network. The interaction between the central nervous system and the surrounding environment is shown to (...) perform a quantum measurement upon the neural constituents, which actualize a single measurement outcome selected from the resulting quantum probability distribution. Inherent biases in the quantum propensities for alternative physical outcomes provide varying amounts of free will, which can be quantified with the expected information gain from learning the actual course of action chosen by the nervous system. For example, neuronal electric spikes evoke deterministic synaptic vesicle release in the synapses of sensory or somatomotor pathways, with no free will manifested. In cortical synapses, however, vesicle release is triggered indeterministically with probability of 0.35 per spike. This grants the brain cortex, with its over 100 trillion synapses, an amount of free will exceeding 96 terabytes per second. Although reliable deterministic transmission of sensory or somatomotor information ensures robust adaptation of animals to their physical environment, unpredictability of behavioral responses initiated by decisions made by the brain cortex is evolutionary advantageous for avoiding predators. Thus, free will may have a survival value and could be optimized through natural selection. (shrink)

The discovery of participation of astrocytes as active elements in glutamatergic tripartite synapses (composed by functional units of two neurons and one astrocyte) has led to the construction of models of cognitive functioning in the human brain, focusing on associative learning, sensory integration, conscious processing and memory formation/retrieval. We have modelled human cognitive functions by means of an ensemble of functional units (tripartite synapses) connected by gap junctions that link distributed astrocytes, allowing the formation of intra- and intercellular calcium waves (...) that putatively mediate large-scale cognitive information processing. The model contains a diagram of molecular mechanisms present in tripartite synapses and contributes to explain the physiological bases of cognitive functions. It can be potentially expanded to explain emotional functions and psychiatric phenomena. (shrink)

Long-term potentiation (LTP) is operationally defined as a long-lasting increase in synaptic efficacy following high-frequency stimulation of afferent fibers. Since the first full description of the phenomenon in 1973, exploration of the mechanisms underlying LTP induction has been one of the most active areas of research in neuroscience. Of principal interest to those who study LTP, particularly in the mammalian hippocampus, is its presumed role in the establishment of stable memories, a role consistent with descriptions of memory formation. Other characteristics (...) of LTP, including its rapid induction, persistence, and correlation with natural brain rhythms, provide circumstantial support for this connection to memory storage. Nonetheless, there is little empirical evidence that directly links LTP to the storage of memories. In this target article we review a range of cellular and behavioral characteristics of LTP and evaluate whether they are consistent with the purported role of hippocampal LTP in memory formation. We suggest that much of the present focus on LTP reflects a preconception that LTP is a learning mechanism, although the empirical evidence often suggests that LTP is unsuitable for such a role. As an alternative to serving as a memory storage device, we propose that LTP may serve as a neural equivalent to an arousal or attention device in the brain. Accordingly, LTP may increase in a nonspecific way the effective salience of discrete external stimuli and may thereby facilitate the induction of memories at distant synapses. Other hypotheses regarding the functional utility of this intensely studied mechanism are conceivable; the intent of this target article is not to promote a single hypothesis but rather to stimulate discussion about the neural mechanisms underlying memory storage and to appraise whether LTP can be considered a viable candidate for such a mechanism. (shrink)

The cellular basis of motor learning in the cerebellum has been attributed mostly to long-term depression (LTD) at excitatory parallel fiber (PF)-Purkinje cell (PC) synapses. LTD is induced when PFs are activated in conjunction with a climbing fiber (CF), the other excitatory input to PCs. Recently, by using whole-cell patch-clamp recording from PCs in cerebellar slices, a new form of synaptic plasticity was discovered. Stimulation of excitatory CFs induced a long-lasting (usually longer than 30 min) of 30 sec) and the (...) durations of RP (>30 min) strongly suggests that some intracellular biochemical machinery is involved. Pharmacological evidence suggests that protein kinases are involved in RP of inhibitory synapses and LTD of excitatory PF synapses. Besides the well-described LTD, RP could be a cellular mechanism that plays an important role in motor learning. (shrink)

Les rituels sont les synapses dans le tissu culturel d'où sont issus les éléments qui gouvernent la vie en commun et la communication des êtres humains. Il en est ainsi depuis le commencement de toute société humaine. Mais ce n'est qu'au XX siècle que se manifeste un véritable intérêt pour le fonctionnement et l'importance culturelle des rituels. Il s'agit d'un tournant inspiré par les théories des ethnologues, et placé sous le signe du cultural turn et du performative turn du XX (...) siècle. On se détourne alors des pratiques jusque-là en vigueur de l'abstraction et de la représentation. Or, depuis le «Banquet» de Platon et l'instauration de la «Cène» chrétienne, l'un des rituels les plus importants est l'acte socialement codé de l'ingestion de nourriture, le repas. Avec l'Eat art dont il est le concepteur, Daniel Spoerri a repris ce thème et contribué, par le truchement du rituel piège, à poser un regard neuf sur l'acte de manger au XXe siècle. Tel que Spoerri le met en scène, le «rituel piège» attire l'attention sur le rôle de fondation de sens que joue le rituel dans la culture. Mais il fait apparaître également que les rituels se transforment en pièges idéologiques où tombe quiconque les prend « à la lettre » ou comme des évidences. Spoerri est un des artistes du XX et de ce début du XXI siècle qui, par le biais de leur art, rendent compte de la double fonction du rituel dans la culture: d'une part, le rituel maintient en vie le processus culturel; d'autre part, il est producteur d'idéologies qui font passer des mythes politiques pour naturels, prenant au piège consommateur de nourriture et consommateur d'art tout à la fois.Rituals are the synapses in the cultural fabric which has produced the elements that govern the coexistence and communication of human beings. This is so since the beginning of human society. But it is only 20th century that demonstrates a genuine interest in the operation and cultural importance of rituals. It is a milestone inspired by the theories of ethnologists, and placed under the sign of the cultural turn and performative turn of the twentieth century. It then turns practices far into force of abstraction and representation. However, since the "Banquet" of Plato and the establishment of the "Last Supper" Christian, one of the most important rituals is the act socially coded ingestion of food, meal. Eat with the art of which he is the designer, Daniel Spoerri took up this theme and contributed through the ritual trap, put a new perspective on the act of eating in the twentieth century. Spoerri as the stages, the "ritual trap" draws attention to the role of Foundation meaningful ritual plays in the culture. But it also shows that the rituals are transformed into ideological traps which falls whoever takes "the letter" or as evidence. Spoerri is one of the artists of the 20th and the beginning of the 21st century, through their art, reflect the dual role of ritual in culture: on the one hand, the ritual keeps life the cultural process, on the other hand, it is a producer of ideologies that pass for political myths natural trapping consumer food and consumer of art at the same time. (shrink)

A common misunderstanding of the selected effects theory of function is that natural selection operating over an evolutionary time scale is the only functionbestowing process in the natural world. This construal of the selected effects theory conflicts with the existence and ubiquity of neurobiological functions that are evolutionary novel, such as structures underlying reading ability. This conflict has suggested to some that, while the selected effects theory may be relevant to some areas of evolutionary biology, its relevance to neuroscience is (...) marginal. This line of reasoning, however, neglects the fact that synapses, entire neurons, and potentially groups of neurons can undergo a type of selection analogous to natural selection operating over an evolutionary time scale. In the following, I argue that neural selection should be construed, by the selected effect theorist, as a distinct type of function-bestowing process in addition to natural selection. After explicating a generalized selected effects theory of function and distinguishing it from similar attempts to extend the selected effects theory, I do four things. First, I show how it allows one to identify neural selection as a distinct function-bestowing process, in contrast to other forms of neural structure formation such as neural construction. Second, I defend the view from one major criticism, and in so doing I clarify the content of the view. Third, I examine drug addiction to show the potential relevance of neural selection to neuroscientific and psychological research. Finally, I endorse a modest pluralism of function concepts within biology. (shrink)

Pathogenesis in tauopathies involves the accumulation of tau in the brain and progressive synapse loss accompanied by cognitive decline. Pathological tau is found at synapses, and it promotes synaptic dysfunction and memory deficits. The specific role of toxic tau in disrupting the molecular networks that regulate synaptic strength has been elusive. A novel mechanistic link between tau toxicity and synaptic plasticity involves the acetylation of two lysines on tau, K274, and K281, which are associated with dementia in Alzheimer's disease (...) (AD). We propose that an increase in tau acetylated on these lysines blocks the expression of long‐term potentiation at hippocampal synapses leading to impaired memory in AD. Acetylated tau could inhibit the activity‐dependent recruitment of postsynaptic AMPA‐type glutamate receptors required for plasticity by interfering with the postsynaptic localization of KIBRA, a memory‐associated protein. Strategies that reduce the acetylation of tau may lead to effective treatments for cognitive decline in AD. (shrink)

This paper discusses recent improvements and extensions in Synapse system for inductive inference of context free grammars from sample strings. Synapse uses incremental learning, rule generation based on bottom-up parsing, and the search for rule sets. The form of production rules in the previous system is extended from Revised Chomsky Normal Form A →βγ to Extended Chomsky Normal Form, which also includes A → B, where each of β and γ is either a terminal or nonterminal symbol. From (...) the result of bottom-up parsing, a rule generation mechanism synthesizes minimum production rules required for parsing positive samples. Instead of inductive CYK algorithm in the previous version of Synapse, the improved version uses a novel rule generation method, called ``bridging,'' which bridges the lacked part of the derivation tree for the positive string. The improved version also employs a novel search strategy, called serial search in addition to minimum rule set search. The synthesis of grammars by the serial search is faster than the minimum set search in most cases. On the other hand, the size of the generated CFGs is generally larger than that by the minimum set search, and the system can find no appropriate grammar for some CFL by the serial search. The paper shows experimental results of incremental learning of several fundamental CFGs and compares the methods of rule generation and search strategies. (shrink)

Polarity is an inherent feature of almost all prokaryotic and eukaryotic cells. In most eukaryotic cells, growth polarity is due to the assembly of actin‐based growing domains at particular locations on the cell periphery. A contrasting scenario is that growth polarity results from the establishment of non‐growing domains, which are actively maintained at opposite end‐poles of the cell. This latter mode of growth is common in rod‐shaped bacteria and, surprisingly, also in the majority of plant cells, which elongate along the (...) apical–basal axes of plant organs. The available data indicate that the non‐growing end‐pole domains of plant cells are sites of intense endocytosis and recycling. These actin‐enriched end‐poles serve also as signaling platforms, allowing bidirectional exchange of diverse signals along the supracellular domains of longitudinal cell files. It is proposed that these actively remodeled end‐poles of elongating plant cells remotely resemble neuronal synapses. BioEssays 25:569–576, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:BOOK REVIEWS 341 if you started asking them questions about possible worlds. But Bradley's contribution is to have given us a painstaking and thorough reading of some extremely tightly wound and important aspects of the Tractatus, to have brought that text into direct contaot with con· temporary issues, and to have made progress toward showing that how· ever remarkable we thought the Tractatus was, it is still more remarkable (...) than that. JOHN CHURCHILL Hendrix College Conway, Arkansas The Human Person: Animal and Spirit. By DAVID BRAINE. Notre Dame, Indiana: University of Notre Dame Press, 1992. Pp. xxv + 555. $32.95 (cloth). Any study in philosophical anthropology that rejects both mate· rialism and dualism, and seeks to set forth a " holistic " alternative, may be met in many quarters with some skepticism today-especially if that alternative seeks to accommodate itself to religious teaching regarding the soul's continued existence after death. For, it will be asked, on the one hand, how can it deny that the esse of the human being ceases at death (538) without affirming some sort of dualism? On the other hand, unless it is some sort of soft-headed New Age philosophy (which this most certainly is not), how can it sustain its claim to "holism" while rejecting the monolithic materialism of those whom Walker Percy once described as our "brain engineers, neuropharmacologists, and chemists of the synapses "? The challenge is " how to produce an account which allows the human person to continue exist· ing after death, and even to have body restored to it, while remaining completely faithful to the insight that it belongs to human nature to be bodily," and, at the same time, to " avoid reerecting the soul into a complete substance" (xix). The peculiar obstacle faced by such a project is the pervasive proclivity towards reductionism in modern accounts of human nature stemming from the impress of both materialism and dualism. Both analyze the human person into an aggregate of parts in certain relations, the behavior of the whole being ·the result of the interactions of these parts. " In all this the materialist has exactly the same picture as the dualist. Indeed, unless the mental can first be represented as inner, logically independent of anything in the ' outer man ' and the ' world,' there is no way in which it can be identified with a brain-process or 342 BOOK REVIEWS state" (3). So whether one thinks of the mind as an independent en· tity (as in dualism), or not (as in materialism), the body is left to be accounted for by the brain engineers and their aggregates of physi· ological, anatomical, neurological, and chemical causes. And since materialism involves no complicating questions about causal interaction between the physical and the mental (as in dualism), it is usually preferred on grounds of its simplicity-all causation being subsumed under the physical. In this ambitious tome, David Braine, a philosopher at the University of Aberdeen, offers a thoroughgoing analysis and critique of such views, whereby he undertakes to overturn these ways of viewing human nature and to offer a holistic alternative. He sets forth a framework for understanding things like perceiving, doing, and speaking as irreducibly the acts of the psychosomatically integrated beings to which we normally attribute them-an understanding that conforms to the ordinary experience of such acts in ourselves and in others. He seeks to expose how materialist arguments repeat the mistakes of the dualists by reducing human beings (and other animals) to their aggregate parts, segmented sequences, and their interrelations. He takes issue with the arguments of recent analytical philosophers (such as Davidson and Dummett) in detail, and sets forth a holistic alternative-both with re· spect to the human person as " animal" and as " spirit." As to the human as "animal," Braine notes, accordingly, that "it is the bodily animal being as such, not just its mind, which is an ' I ', a ' he or she ', a focalized subject in relation to the world. The primary reason why human behaviour cannot be simulated by a computer does not lie in things special to human beings, but in the fact that this fo. calized psychophysical structure which they share with the... (shrink)

One of the main issues raised over the years has been how religion feels about music. The relationship between religion and music as a promoting and not a corrupting art is one of the problems that warrants further research in this area. According to this article, phonic music can be a source for various services and be supported by religion in particular circumstances. The article discusses the musical elements of several religious texts, how religion affects the creative process, the human (...) voice, and religious music. In popular music, voices and vocal expression are extremely important. Voices are instantly connected to the body and different emotional states. However, learned cultural patterns of expression can also conventionalize and alter vocal expression; this is true for both music and daily speech. We know from day to day experience that singing might give us energy and, surprisingly, an actual exercise. Anecdotal suggestions that singing is good for your health and happiness are backed up by a growing body of research. It has been demonstrated that singing causes a variety of physiological changes. Persistent singing practice uses the cardiorespiratory system, strengthening the respiratory muscles and improving breathing efficiency. The up rule of oxytocin, immunoglobulin A, and endorphins, which work on immunological capacity and raise impressions of joy, is only one of the progressions in synapses and chemicals that singing can achieve. In this essay, we examine the role that religious singing plays in promoting the vocal arts. (shrink)

In this multidisciplinary book, mathematician Matthew He provides integrative perspectives of algebraic biology, cognitive informatics, and poetic expressions of the human mind. Using classical Pythagorean Theorem and contemporary Category Theory, the proposed matrix models of the human mind connect three domains of the physical space of objective matters, mental space of subjective meanings, and emotional space of bijective modes; draws the connections between neural sparks and idea points, between synapses and idea lines, and between action potentials and frequency curves.

The posterior parietal cortex (PPC) is the most likely site where egocentric spatial relationships are represented in the brain. PPC cells receive visual, auditory, somaesthetic, and vestibular sensory inputs; oculomotor, head, limb, and body motor signals; and strong motivational projections from the limbic system. Their discharge increases not only when an animal moves towards a sensory target, but also when it directs its attention to it. PPC lesions have the opposite effect: sensory inattention and neglect. The PPC does not seem (...) to contain a “map” of the location of objects in space but a distributed neural network for transforming one set of sensory vectors into other sensory reference frames or into various motor coordinate systems. Which set of transformation rules is used probably depends on attention, which selectively enhances the synapses needed for making a particular sensory comparison or aiming a particular movement. (shrink)

Recent advances in neuroscience lead to a wider realm for philosophy to include the science of the Darwinian-evolved computational brain, our inner world producing organ, a non-recursive super- Turing machine combining 100B synapsing-neuron DNA-computers based on the genetic code. The whole system is a logos machine offering a world map for global context, essential for our intentional grasp of opportunities. We start from the observable contrast between the chaotic universe vs. our orderly inner world, the noumenal cosmos. So far, philosophy (...) has been rehearsing our thoughts, our human-internal world, a grand painting of the outer world, how we comprehend subjectively our experience, worked up by the logos machine, but now we seek a wider horizon, how humans understand the world thanks to Darwinian evolution to adapt in response to the metaphysical gap, the chasm between the human animal and its environment, shaping the organism so it can deal with its variable world. This new horizon embraces global context coded in neural structures that support the noumenal cosmos, our inner mental world, for us as denizens of the outer environment. Kant’s inner and outer senses are fundamental ingredients of scientific philosophy. Several sections devoted to Heidegger, his lizard debunked, but his version of the metaphysical gap & his doctrine of the logos praised. Rorty and others of the behaviorist school discussed also. (shrink)

During the past two decades, philosophers of biology have increasingly turned their attention to mechanisms of biological phenomena. Through analyses of mechanistic proposals advanced by biologists, the goal of these philosophers is to understand what a mechanism is and how mechanisms explain. These analyses have generally focused on mechanistic proposals for phenomenon that occur at the cellular or sub-cellular level, such as synapse firing, protein synthesis, or metabolic pathway operation. Little is said about the mechanisms of the macromolecular reactions (...) that underpin these phenomena. These reactions comprise a diverse family of reaction types, and include protein folding, macromolecular complex formation, receptor-ligand interactions, and enzyme catalysis. In this paper, I develop an account of mechanism that focuses exclusively on macromolecular reactions. I begin by reviewing how mechanism is understood in enzymology, and how mechanistic concepts of enzymology apply to macromolecular reactions in general. We will see that the mechanism of a macromolecular reaction is most accurately described as a progression of reaction intermediates, where the evolution of intermediates, from one to the next, is characterized by an energetic coupling between chemistry and protein dynamics. I then make the case that this description necessitates a grounding in a process ontology. To describe the mechanism by which a macromolecular reaction occurs is to describe a process. (shrink)