Information processing in the brain depends on the integration of synaptic input distributed throughout neuronal dendrites. Dendritic integration is a hierarchical process, proposed to be equivalent ...to integration by a multilayer network, potentially endowing single neurons with substantial computational power. However, whether neurons can learn to harness dendritic properties to realize this potential is unknown. Here, we develop a learning rule from dendritic cable theory and use it to investigate the processing capacity of a detailed pyramidal neuron model. We show that computations using spatial or temporal features of synaptic input patterns can be learned, and even synergistically combined, to solve a canonical nonlinear feature-binding problem. The voltage dependence of the learning rule drives coactive synapses to engage dendritic nonlinearities, whereas spike-timing dependence shapes the time course of subthreshold potentials. Dendritic input-output relationships can therefore be flexibly tuned through synaptic plasticity, allowing optimal implementation of nonlinear functions by single neurons.
Display omitted
•A learning rule derived from cable theory is used in biophysical simulations•Pyramidal cell I/O functions can be optimized for computation by synaptic plasticity•Active and passive dendritic mechanisms enhance input pattern discrimination•Single neurons can learn network-level computations simply by tuning synaptic weights
Bicknell and Häusser develop a theoretical approach for investigating single-neuron computation and learning. By deriving a plasticity rule that optimally adjusts the strengths of interacting synapses to control somatic spiking, they show that neurons can learn to harness the biophysical properties of their dendrites to perform nonlinear computations.
The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the ...neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behavior has not yet been demonstrated. Using an ‘all-optical’ combination of simultaneous two-photon calcium imaging and two-photon optogenetics, we identified and selectively activated place cells that encoded behaviorally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behavior of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory.
Display omitted
•Two-photon optogenetics in VR enables targeted manipulation of place cell ensembles•Activating specific place cell ensembles drives their spatially associated behavior•Place cell stimulation inhibits endogenous place code expression and triggers remapping•Direct evidence for a causal role of place cells in spatial navigation
Selective stimulation of a small number of hippocampal place cells in mice provides causal evidence that hippocampal place cells actively support spatial navigation and memory.
The development of a functional nervous system requires tight control of neurite growth and guidance by extracellular chemical cues. Neurite growth is astonishingly sensitive to shallow concentration ...gradients, but a widely observed feature of both growth and guidance regulation, with important consequences for development and regeneration, is that both are only elicited over the same relatively narrow range of concentrations. Here we show that all these phenomena can be explained within one theoretical framework. We first test long-standing explanations for the suppression of the trophic effects of nerve growth factor at high concentrations, and find they are contradicted by experiment. Instead we propose a new hypothesis involving inhibitory signalling among the cell bodies, and then extend this hypothesis to show how both growth and guidance can be understood in terms of a common underlying signalling mechanism. This new model for the first time unifies several key features of neurite growth regulation, quantitatively explains many aspects of experimental data, and makes new predictions about unknown details of developmental signalling.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many ion channels exhibit a slow stochastic switching between distinct modes of gating activity. This feature of channel behavior has pronounced implications for the dynamics of ionic currents and ...the signaling pathways that they regulate. A canonical example is the inositol 1,4,5-trisphosphate receptor (IP₃R) channel, whose regulation of intracellular Ca2+ concentration is essential for numerous cellular processes. However, the underlying biophysical mechanisms that give rise to modal gating in this and most other channels remain unknown. Although ion channels are composed of protein subunits, previous mathematical models of modal gating are coarse grained at the level of whole-channel states, limiting further dialogue between theory and experiment. Here we propose an origin for modal gating, by modeling the kinetics of ligand binding and conformational change in the IP₃R at the subunit level. We find good agreement with experimental data over a wide range of ligand concentrations, accounting for equilibrium channel properties, transient responses to changing ligand conditions, and modal gating statistics. We show how this can be understood within a simple analytical framework and confirm our results with stochastic simulations. The model assumes that channel subunits are independent, demonstrating that cooperative binding or concerted conformational changes are not required for modal gating. Moreover, the model embodies a generally applicable principle: If a timescale separation exists in the kinetics of individual subunits, then modal gating can arise as an emergent property of channel behavior.
Many biological processes rely on the ability of cells to measure local ligand concentration. However, such measurements are constrained by noise arising from diffusion and the stochastic nature of ...receptor-ligand interactions. It is thus critical to understand how accurately, in principle, concentration measurements can be made. Previous theoretical work has mostly investigated this in 3D under the simplifying assumption of an unbounded domain of diffusion, but many biological problems involve 2D concentration measurement in bounded domains, for which diffusion behaves quite differently. Here we present a theory of the precision of chemosensation that covers bounded domains of any dimensionality. We find that the quality of chemosensation in lower dimensions is controlled by domain size, suggesting a general principle applicable to many biological systems. Applying the theory to biological problems in 2D shows that diffusion-limited signalling is an efficient mechanism on time scales consistent with behaviour.
Chemotaxis plays a key role in many biological systems. In particular in the context of the developing nervous system, growing neurites can respond in vitro to shallow gradients of chemotropic ...molecules such as nerve growth factor (NGF). However, in such studies the gradient parameters are often not well controlled. Here we present a dataset of ~3500 images of early postnatal rat dorsal root ganglion (DRG) explants growing in 40 different precisely controlled combinations of absolute concentration and gradient steepness of NGF. Each image has been segmented into neurite and explant-body regions. We provide computer code for exploration and quantification of the data, including a Fourier analysis of the outer contour of neurite growth, which allows quantities such as outgrowth and guidance as a function of concentration and gradient steepness to be easily extracted. This is the most comprehensive quantitative dataset of chemotactic responses yet available for any biological system, which we hope will be useful for exploring the biological mechanisms governing chemotaxis.
The dynamics of growth cone morphology Goodhill, Geoffrey J; Faville, Richard A; Sutherland, Daniel J ...
BMC biology,
2015-Feb-11, 2015-2-11, 20150211, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Normal brain function depends on the development of appropriate patterns of neural connections. A critical role in guiding axons to their targets during neural development is played by neuronal ...growth cones. These have a complex and rapidly changing morphology; however, a quantitative understanding of this morphology, its dynamics and how these are related to growth cone movement, is lacking.
Here we use eigenshape analysis (principal components analysis in shape space) to uncover the set of five to six basic shape modes that capture the most variance in growth cone form. By analysing how the projections of growth cones onto these principal modes evolve in time, we found that growth cone shape oscillates with a mean period of 30 min. The variability of oscillation periods and strengths between different growth cones was correlated with their forward movement, such that growth cones with strong, fast shape oscillations tended to extend faster. A simple computational model of growth cone shape dynamics based on dynamic microtubule instability was able to reproduce quantitatively both the mean and variance of oscillation periods seen experimentally, suggesting that the principal driver of growth cone shape oscillations may be intrinsic periodicity in cytoskeletal rearrangements.
Intrinsically driven shape oscillations are an important component of growth cone shape dynamics. More generally, eigenshape analysis has the potential to provide new quantitative information about differences in growth cone behaviour in different conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human activities have fundamentally altered the marine environment, creating a need for effective management in one of Earth's most challenging habitats. Remote camera imagery has emerged as an ...essential tool for monitoring at all scales, from individuals to populations and communities up to entire marine ecosystems. Here we review the use of remote cameras to monitor the marine environment in relation to human activity, and consider emerging and potential future applications. Rapid technological advances in equipment and analytical tools influence where, why, and how remote camera imagery can be applied. We encourage the inclusion of cameras within multi-method and multi-sensor approaches to improve our understanding of ecosystems and help manage human activities and minimize impacts.
PDF
