Wiring optimization in cortical circuits

Wiring a brain presents a formidable problem because neural circuits require an enormous number of fast and durable connections. We propose that evolution was likely to have optimized neural circuits to minimize conduction delays in axons, passive cable attenuation in dendrites, and the length of "wire" used to construct circuits, and to have maximized the density of synapses. Here we ask the question: "What fraction of the volume should be taken up by axons and dendrites (i.e., wire) when these variables are at their optimal values?" The biophysical properties of axons and dendrites dictate that wire should occupy 3/5 of the volume in an optimally wired gray matter. We have measured the fraction of the volume occupied by each cellular component and find that the volume of wire is close to the predicted optimal value.     

Wiring and rewiring of the retinogeniculate synapse

The formation and refinement of synaptic circuits are areas of research that have fascinated neurobiologists for decades. A recurrent theme seen at many CNS synapses is that neuronal connections are at first imprecise, but refine and can be rearranged with time or with experience. Today, with the advent of new technologies to map and monitor neuronal circuits, it is worthwhile to revisit a powerful experimental model for examining the development and plasticity of synaptic circuits--the retinogeniculate synapse.     

Multicellular Computing Using Conjugation for Wiring

Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal “re-programming” and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a “computation” is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the “wiring” between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing system under different conditions, and provide baseline information for future laboratory implementations.     

Wiring specificity in the olfactory system

The fruitfly brain learns about the olfactory world by reading the activity of about 50 distinct channels of incoming information. The receptor neurons that compose each channel have their own distinctive odour response profile governed by a specific receptor molecule. These receptor neurons form highly specific connections in the first olfactory relay of the fly brain, each synapsing with specific second order partner neurons. We use this system to discuss the logic of wiring specificity in the brain and to review the cellular and molecular mechanisms that allow such precise wiring to develop.     

Molecular Wiring of a Mitochondrial Translational Feedback Loop

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Wiring step-wise reactions with immobilized multi-enzyme systems

Abstract

The immobilization of multi-enzyme systems on advanced materials is an emerging technology inspired by the spatial localization found in Nature. These systems harness the high chemo-, regio- and stereoselectivity of the enzymes and the heterogeneous nature of the resulting biocatalyst. This synergy allows more efficient and selective synthetic schemes which reduce waste production and simplify downstream processing. The revolution of the nanotechnology has contributed to design advanced materials that allow precisely controlling the spatial distribution of the different catalytic modules forming a multi-enzyme system. Outstandingly, this fact has boosted the development and the improvement of more complex cascade reactions catalyzed in vitro by heterogeneous multi-functional biocatalysts. In this review, we have discussed the different challenges that must be faced during the immobilization of multi-enzyme systems; from the carrier surface to the incorporation of cofactors into the solid-phase. We have analyzed how the physico-chemical properties of the solid materials affect the efficiency of the multi-enzyme systems and how enzymes can be co-immobilized to optimize their performance as a cascade. We have also discussed the effect of the architecture and spatial organization of the enzymes on the productivity of the system. Furthermore, we have given some clues to coordinate both activity and stability of individual enzymes to orchestrate their performance towards the necessities of the reaction cascade. Finally, we have summarized the last advances for the incorporation of biological cofactors into the solid-phase to fabricate self-sufficient heterogeneous biocatalyst that do not require the exogenous addition of those expensive cofactors. Therefore, the main goal of this review is presenting to the biocatalysis community the available tools to implement immobilized enzymatic cascades into synthetic, analytical, medical and environmental chemistry.     

Mechanisms and Molecules of Neuronal Wiring: A Primer

The complex patterns of neuronal wiring in the adult nervous system depend on a series of guidance events during neural development that establish a framework on which functional circuits can be built. In this subject collection, the cellular and molecular mechanisms that underlie neuronal guidance are considered from several perspectives, ranging from how cytoskeletal dynamics within extending neuronal growth cones steer axons, to how guidance cues influence synaptogenesis. We introduce here some basic topics to frame the more detailed reviews in following articles, including the cellular strategies that define basic themes governing neuronal wiring throughout life, an enumeration of the molecular cues and receptors known to play key guidance roles during neural development, and an overview of the signaling mechanisms that transduce guidance information into growth-cone steering.Nerve processes extend toward their immediate and final targets with remarkable precision. At the tip of an extending axon is a flattened, fan-shaped structure called a growth cone, with many long, thin spikes that radiate outward much like fingers on a glove. Classical observations of neuronal growth cones and the formation of axonal and dendritic trajectories during neural development led to the conclusion that extrinsic cues must exist that have the capacity to steer extending neuronal processes. For over 100 years, neuroscientists have searched for these cues, their cell surface receptors, and an understanding of how the cues signal spatial information to the extending neuronal processes to direct neural circuit formation.A wealth of cellular observations indicate that growth cones are actively directed along their prescribed pathways. In this collection, Raper and Mason review the extensive body of experiments that support this view (Raper and Mason 2010). These studies reveal that neural wiring occurs through a combination of initial neuronal activity-independent guidance events, and that these early formed connections are subsequently refined through electrical signaling among neurons. The cues that initially guide axons and dendrites can function at both long and short ranges, and they are capable of influencing the bundling of axons together into nerves or fascicles (termed “fasciculation”) and also of mediating interactions between nerves and the substrates on which they extend (Fig. 1). Guidance cues associated with particular intermediate or final targets can be chemoattractive or chemorepulsive, and provide the information essential for selective guidance of distinct neuronal populations. Sequential responses to guidance cues as axons extend over very long distances toward their targets allow for complex pathways to develop, but this often requires that neurons extinguish their responses to certain cues and acquire responsiveness to others at key choice points. Much work over the past several decades has been devoted to identifying these guidance cues and their receptors, and to understanding how cellular responses to these cues change to allow for guidance of extending neuronal processes along discrete segments of their journey to their final targets.Open in a separate windowFigure 1.The diversity of neuronal guidance mechanisms. Neuronal processes are guided by cues that can function at long and short distances to mediate either attractive or repulsive guidance.     

Wiring the zebrafish: axon guidance and synaptogenesis

Many zebrafish mutants have specific defects in axon guidance or synaptogenesis, particularly in the retinotectal and motor systems. Several mutants have now been characterized in detail and/or cloned. A combination of genetic studies, in vivo imaging and new techniques for misexpressing genes or blocking their function promises to reveal the molecules and principles that govern wiring of the vertebrate nervous system.     

Genetic Control of Wiring Specificity in the Fly Olfactory System

Precise connections established between pre- and postsynaptic partners during development are essential for the proper function of the nervous system. The olfactory system detects a wide variety of odorants and processes the information in a precisely connected neural circuit. A common feature of the olfactory systems from insects to mammals is that the olfactory receptor neurons (ORNs) expressing the same odorant receptor make one-to-one connections with a single class of second-order olfactory projection neurons (PNs). This represents one of the most striking examples of targeting specificity in developmental neurobiology. Recent studies have uncovered central roles of transmembrane and secreted proteins in organizing this one-to-one connection specificity in the olfactory system. Here, we review recent advances in the understanding of how this wiring specificity is genetically controlled and focus on the mechanisms by which transmembrane and secreted proteins regulate different stages of the Drosophila olfactory circuit assembly in a coordinated manner. We also discuss how combinatorial coding, redundancy, and error-correcting ability could contribute to constructing a complex neural circuit in general.     

Wiring the nervous system: from form to function

The RIKEN Centre for Developmental Biology recently hosted a joint UK-Asian Pacific Developmental Biology Network meeting called 'Development and Emergence of Function in the Nervous System'. The meeting's program, which was organized by James Briscoe and Krishnaswamy VijayRaghavan, covered a spectrum of processes and mechanisms in neurodevelopment, ranging from the patterning of neural tissue to the initiation of a functional nervous system. One idea to have emerged during this meeting is that 'form underlies function'. Here we discuss some of the themes that were addressed and provide a broad impression of what was a highly stimulating and successful conference.     

Wiring specificity: axon-dendrite matching refines the olfactory map

In Drosophila, about 50 classes of olfactory receptor neurons enter the brain where their axons form highly specific synapses with the dendrites of identified partner neurons. A recent study has shown that genetic manipulations that shift the position of one class of postsynaptic dendrites can cause an exact corresponding shift in the location of their partner axons.     

Branched Signal Wiring of an Essential Bacterial Cell-Cycle Phosphotransfer Protein

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