Fred Wolf

• Max Planck Institute for Dynamics and Self-Organization

Nerve impulses, the currency of information flow in the brain, are generated by an instability of the neuronal membrane potential dynamics. Neuronal circuits exhibit collective chaos that appears essential for learning, memory, sensory processing, and motor control. However, the factors controlling the nature and intensity of collective chaos in ne...

The synaptic vesicle cluster (SVC) is an essential component of chemical synapses, which provides neurotransmitter‐loaded vesicles during synaptic activity, at the same time as also controlling the local concentrations of numerous exo‐ and endocytosis cofactors. In addition, the SVC hosts molecules that participate in other aspects of synaptic func...

Adherens junctions are very plastic structures that change their composition and structure depending on the state of the epithelial tissue, involving mechanical stress and tissue dynamics. In Drosophila embryos, adherens junctions mature only during gastrulation following their formation a few minutes before during cellularization. Although the dev...

Cortical function reflects the coordinated activities of populations of neurons, which, in turn, depend on the speed with which each neuron can respond to input, as revealed by dynamic gain analysis. In Layer 4 of the rodent barrel cortex, a finite population of interconnected, small, excitatory neurons rapidly and briefly relays input from the spe...

Modern, high-density neuronal recordings reveal at ever higher precision how information is represented by neural populations. Still, we lack the tools to understand these processes bottom-up, emerging from the biophysical properties of neurons, synapses, and network structure. The concept of the dynamic gain function, a spectrally resolved approxi...

Neuronal spiking activity in cortical circuits is often temporally structured by collective rhythms. Rhythmic activity has been hypothesized to regulate temporal coding and to mediate the flexible routing of information flow across the cortex. Spiking neuronal circuits, however, are non-linear systems that, through chaotic dynamics, can amplify ins...

Neuronal spiking activity in cortical circuits is often temporally structured by collective rhythms. Rhythmic activity has been hypothesized to regulate temporal coding and to mediate the flexible routing of information flow across the cortex. Spiking neuronal circuits, however, are non-linear systems that, through chaotic dynamics, can amplify ins...

Cell–cell adhesion is at the center of structure and dynamics of epithelial tissue. E-cadherin–catenin complexes mediate Ca2+-dependent trans-homodimerization and constitute the kernel of adherens junctions. Beyond the basic function of cell–cell adhesion, recent progress sheds light the dynamics and interwind interactions of individual E-cadherin–...

This article is part of the Physical Review Research collection titled Physics of Neuroscience.

Aims Fibroblast growth factor (FGF) signalling is dysregulated in multiple sclerosis (MS) and other neurological and psychiatric conditions, but there is little or no consensus as to how individual FGF family members contribute to disease pathogenesis. Lesion development in MS is associated with increased expression of FGF1, FGF2 and FGF9, all of w...

Rods under mechanical stress are a classic example of dynamic instability. Axis elongation in Drosophila usually leads to a U-shaped axis, but folded or twisted axes are observed in certain mutants. Analysis of these mutants now reveals the source of the instability and the mechanism for maintaining left-right symmetry.

Distributions of neuronal activity within cortical circuits are often found to display highly skewed shapes with many neurons emitting action potentials at low or vanishing rates, while some are active at high rates. Theoretical studies were able to reproduce such distributions, but come with a lack of mathematical tractability, preventing a deeper...

During embryonic development dramatic cell shape changes and movements re-shape the embryonic body plan. These require robust but dynamic linkage between the cell-cell adherens junctions and the force-generating actomyosin cytoskeleton. Our view of this linkage has evolved, and we now realize linkage is mediated by mechanosensitive multiprotein com...

Finite time convergence to functionally important target states is a key component of many biological processes. We previously found that the terminal approach phase of such dynamics exhibits universal types of stochastic dynamics that differ qualitatively between noise-dominated and force-dominated regimes of the approach dynamics. While for the n...

The dynamics of living systems often serves the purpose of reaching functionally important target states. We previously proposed a theory to analyze stochastic biological dynamics evolving towards target states in reverse time. However, a large class of systems in biology can only be adequately described using state-dependent noise, which had not b...

Mesoscopic bio-systems typically evolve towards functionally important target states, such as cell-cycle checkpoints or decision boundaries for the release of specific behaviors. For the data-driven inference of the underlying directional out-of-equilibrium dynamics, we here develop a theory of target state aligned (TSA) ensembles. Target state ali...

During embryonic development dramatic cell shape changes and movements re-shape the embryonic body plan. These require robust but dynamic linkage between the cell-cell adherens junctions and the force-generating actomyosin cytoskeleton. Our view of this linkage has evolved, and we now realize linkage is mediated by a mechanosensitive multiprotein c...

Neuronal spiking activity in cortical circuits is often temporally structured by collective rhythms. Rhythmic activity has been hypothesized to regulate temporal coding and to mediate the flexible routing of information flow across the cortex. Spiking neuronal circuits, however, are non-linear systems that, through chaotic dynamics, can amplify ins...

Synaptic plasticity underlies long-lasting structural and functional changes to brain circuitry and its experience-dependent remodeling can be fundamentally enhanced by environmental enrichment. It is however unknown, whether and how the environmental enrichment alters the morphology and dynamics of individual synapses. Here, we present a virtually...

Modern, high-density neuronal recordings reveal at ever higher precision how information is represented by neural populations. Still, we lack the tools to understand these processes bottom-up, emerging from the biophysical properties of neurons, synapses, and network structure. The concept of the dynamic gain function, a spectrally resolved approxi...

Populations of cortical neurons respond to common input within a millisecond. Morphological features and active ion channel properties were suggested to contribute to this astonishing processing speed. Here we report an exhaustive study of ultrafast population coding for varying axon initial segment (AIS) location, soma size, and axonal current pro...

Significance Rhythmic brain activity is a signature of information processing. Common inhibitory cells, spike-frequency adapting interneurons, are typically thought to only participate in low-frequency rhythms (<10 Hz). However, we found that these cells’ frequency preference can be switched from 2 to 200 Hz. The switch occurs when low-frequency co...

Recent reports of the lack of periodic orientation columns in a very large rodent species, the red-rumped agouti, and the existence of incompressible hypercolumns in the lineage of primates, as demonstrated in one of the smallest primates, the mouse lemur, strengthen the interpretation that salt-and-pepper and columns-and-pinwheel mosaics are two d...

Excitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption and the storage of long-term information, spines need to be plastic and stable at the same time. Here, we advanced in vivo STED nanoscopy to superresolve distinct features of spines (head size and neck length/width)...

In the brain, spatial information is represented by neurons that fire when an animal is at specific locations, including place cells in hippocampus and grid cells in entorhinal cortex. But how this information is processed in downstream brain regions still remains elusive. Using chronic Ca2+ imaging, we examined the activity of neurons in anterior...

Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. In the present study, we use functional and structural in vivo imaging in a mouse model of cortical MS to d...

All rodents investigated so far possess orientation-selective neurons in primary visual cortex (V1) but - in contrast to carnivores and primates - no evidence of periodic maps with pinwheel-like structures. Theoretical studies debating whether phylogeny or universal principles determine development of pinwheels point to V1 size as critical constrai...

Orientation preference maps (OPMs) are a prominent feature of primary visual cortex (V1) organization in many primates and carnivores. In rodents, neurons are not organized in OPMs but are instead interspersed in a “salt and pepper” fashion, although clusters of orientation-selective neurons have been reported. Does this fundamental difference refl...

Synaptic plasticity underlies long-lasting structural and functional changes to brain circuitry and its experience-dependent remodeling can be fundamentally enhanced by environmental enrichment. It is unknown, however, whether and how environmental enrichment alters the morphology and dynamics of individual synapses. Here, we present a virtually cr...

Excitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption as well as the storage of long-term information, spines need to be plastic and stable at the same time. Here we advanced in vivo STED nanoscopy to superresolve distinct features of dendritic spines (head size, neck...

In the hippocampus, locations associated with salient features are represented by a disproportionately large number of neurons, but the cellular and molecular mechanisms underlying this over-representation remain elusive. Using longitudinal calcium imaging in mice learning to navigate in virtual reality, we find that the over-representation of rewa...

Brains process information through the collective dynamics of large neural networks. Collective chaos was suggested to underlie the complex ongoing dynamics observed in cerebral cortical circuits and determine the impact and processing of incoming information streams. In dissipative systems, chaotic dynamics takes place on a subset of phase space o...

Identifying effective treatments for Alzheimer’s disease (AD) has proven challenging and has instigated a shift in AD research focus toward the earliest disease-initiating cellular mechanisms. A key insight has been an increase in soluble Aβ oligomers in early AD that is causally linked to neuronal and circuit hyperexcitability. However, other accu...

Real-world agents, humans as well as animals, observe each other during interactions and choose their own actions taking the partners’ ongoing behaviour into account. Yet, classical game theory assumes that players act either strictly sequentially or strictly simultaneously without knowing each other’s current choices. To account for action visibil...

Gamma oscillations in cortical circuits critically depend on GABAergic interneurons. Precisely which interneuron types and populations can drive cortical gamma, however, remains unresolved and may depend on brain state. Here we show that spike-frequency adapting interneurons dramatically boost their gamma-sensitivity in the presence of slowly fluct...

The spatial and temporal dynamics of cell contractility plays a key role in tissue morphogenesis, wound healing, and cancer invasion. Here, we report a simple optochemical method to induce cell contractions in vivo during Drosophila morphogenesis at single-cell resolution. We employed the photolabile Ca2+ chelator o-nitrophenyl EGTA to induce burst...

Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. Here we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that b...

Cortical regions that are damaged by insults, such as ischemia, hypoxia, and trauma, frequently generate spreading depolarization (SD). At the neuronal level, SDs entail complete breakdown of ionic gradients, persisting for seconds to minutes. It is unclear whether these transient events have a more lasting influence on neuronal function. Here, we...

Cortical circuits operate in an inhibition-dominated regime of spiking activity. Recently, it was found that spiking circuit models in this regime can, despite disordered connectivity and asynchronous irregular activity, exhibit a locally stable dynamics that may be used for neural computation. The lack of existing mathematical tools has precluded...

A Transparent game is a game-theoretic setting that takes action visibility into account. In each round, depending on the relative timing of their actions, players have a certain probability to see their partner’s choice before making their own decision. This probability is determined by the level of transparency. At the two extremes, a game with z...

A Transparent game is a game-theoretic setting that takes action visibility into account. In each round, depending on the relative timing of their actions, players have a certain probability to see their partner's choice before making their own decision. This probability is determined by the level of transparency. At the two extremes, a game with z...

For humans and for non-human primates heart rate is a reliable indicator of an individual’s current physiological state, with applications ranging from health checks to experimental studies of cognitive and emotional state. In humans, changes in the optical properties of the skin tissue correlated with cardiac cycles (imaging photoplethysmogram, iP...

The spatial and temporal dynamics of cell contractility plays a key role in tissue morphogenesis, wound healing and cancer invasion. Here we report a simple, single cell resolution, optochemical method to induce minute-scale cell contractions in vivo during morphogenesis. We employed the photolabile Ca2+ chelator o-nitrophenyl EGTA to induce bursts...

Central neurons initiate action potentials (APs) in the axon initial segment (AIS), a compartment characterized by a high concentration of voltage-dependent ion channels and specialized cytoskeletal anchoring proteins arranged in a regular nanoscale pattern. Although the AIS was a key evolutionary innovation in neurons, the functional benefits it c...

Optogenetic tools, providing non‐invasive control over selected cells, have the potential to revolutionize sensory prostheses for humans. Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in cochlear implants. However, most channelrhodopsins do not support the high temp...

For humans and for non-human primates heart rate is a reliable indicator of an individual’s current physiological state, with applications ranging from health checks to experimental studies of cognitive and emotional state. In humans, changes in the optical properties of the skin tissue correlated with cardiac cycles (imaging photoplethysmogram, iP...

Comparison of imaging photoplethysmogram with a contact photoplethysmogram. (A) Imaging photoplethysmogram (iPPG) aligns with contact photoplethysmogram (PPG) recorded using pulse oximeter P-OX100L (Medlab GmbH, Stutensee; documented accuracy ± 1%) for Session 8 (in addition to the basic reference pulse oximetry, which was the same as for other ses...

Cortical neurons in the fluctuation driven regime can realize ultrafast population encoding. The underlying biophysical mechanisms, however, are not well understood. Reducing the sharpness of the action potential onset can impair ultrafast population encoding, but it is not clear whether a sharp action potential onset is sufficient for ultrafast po...

Significance Under most conditions cortical pyramidal neurons are strongly biased to initiate action potentials in the distal part of the axon initial segment (AIS) rather than in the dendrites, where the excitatory postsynaptic potential amplitude is largest. This feature is widely attributed to the axonal presence of the low-threshold Na ⁺ channe...

Cortical neurons in the fluctuation driven regime can realize ultrafast population encoding. The underlying biophysical mechanisms, however, are not well understood. Reducing action potential onset rapidness can impair the ultrafast population encoding, but it is not clear whether rapid action potential onset is sufficient for ultrafast population...

Real-world agents, such as humans, animals and robots, observe each other during interactions and choose their own actions taking the partners' ongoing behaviour into account. Yet, classical game theory assumes that players act either strictly sequentially or strictly simultaneously (without knowing the choices of each other). To account for action...

A central problem in biomedical imaging is the automated segmentation of images for further quantitative analysis. Recently, fully convolutional neural networks, such as the U-Net, were applied successfully in a variety of segmentation tasks. A downside of this approach is the requirement for a large amount of well-prepared training samples, consis...

For humans and for non-human primates heart rate is a reliable indicator of an individual’s current physiological state, with applications ranging from health checks to experimental studies of cognitive and emotional state. In humans, changes in the optical properties of the skin tissue correlated with cardiac cycles (imaging photoplethysmogram, iP...

In central neurons, action potentials (APs) originate in the axon initial segment (AIS) presumably due to its high concentration of voltage-dependent sodium (NaV) channels. In the AIS, NaV and their cytoskeletal anchoring proteins display a highly periodical nanoscale arrangement with unknown functional relevance. In mouse hippocampal neurons, we e...

Perception, cognition and behavior rely on flexible communication between microcircuits in distinct cortical regions. The mechanisms underlying rapid information rerouting between such microcircuits are still unknown. It has been proposed that changing patterns of coherence between local gamma rhythms support flexible information rerouting. The sto...

Synaptic interactions structure the phase space of the dynamics of neural circuits and constrain neural computation. Understanding how requires methods that handle those discrete interactions, yet few exist. Recently, it was discovered that even random networks exhibit dynamics that partitions the phase space into numerous attractor basins. Here we...

Body axis elongation by convergent extension is a conserved developmental process found in all metazoans. Drosophila embryonic germ-band extension is an important morphogenetic process during embryogenesis, by which the length of the germ-band is more than doubled along the anterior-posterior axis. This lengthening is achieved by typical convergent...

Synaptic interactions structure the phase space of the dynamics of neural circuits and constrain neural computation. Understanding how requires methods that handle those discrete interactions, yet few exist. Recently, it was discovered that even random networks exhibit dynamics that partitions the phase space into numerous attractor basins. Here we...

Cortical neurons represent information as a population in their collective firing rate. The ability of every individual neuron in this population to fire temporally locked to a stimulus can be expressed, in the frequency domain, by a transfer function or dynamic gain. This transfer function captures the population’s response properties for the line...

Neuronal activity in the central nervous system varies strongly in time and across neuronal populations. It is a longstanding proposal that such fluctuations generically arise from chaotic network dynamics. Various theoretical studies predict that the rich dynamics of rate models operating in the chaotic regime can subserve circuit computation and...

The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics-integration and resonance-have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its eff...

The response of a neuronal population over a space of inputs depends on the intrinsic properties of its constituent neurons. Two main modes of single neuron dynamics-integration and resonance-have been distinguished. While resonator cell types exist in a variety of brain areas, few models incorporate this feature and fewer have investigated its eff...

The architecture of iso-orientation domains in the primary visual cortex of placental carnivores and primates apparently follows species invariant quantitative laws. Dynamical optimization models assuming that neurons coordinate their stimulus preferences throughout cortical circuits linking millions of cells specifically predict these invariants....

Background: Multi-electrode arrays (MEAs) allow non-invasive multi-unit recording in-vitro from cultured neuronal networks. For sufficient neuronal growth and adhesion on such MEAs, substrate preparation is required. Plating of dissociated neurons on a uniformly prepared MEA's surface results in the formation of spatially extended random networks...

Spontaneous bursting activity in cultured neuronal networks is initiated by leader neurons, which constitute a small subset of first-to-fire neurons forming a sub-network that recruits follower neurons into the burst. While the existence and stability of leader neurons is well established, the influence of stimulation on the leader-follower dynamic...

Background Multi-electrode arrays (MEAs) allow non-invasive multiunit recording in-vitro from cultured neuronal networks. For sufficient neuronal growth and adhesion on such MEAs, substrate preparation is required. Plating of dissociated neurons on a uniformly prepared MEA’s surface results in the formation of spatially extended random networks wit...

Somatic action potentials (AP) of cortical pyramidal neurons have characteristically high onset-rapidness. The onset of the AP waveform is an indirect measure for the ability of a neuron to respond to temporally fast-changing stimuli. Theoretical studies on the pyramidal neuron response usually involves a canonical Hodgkin-Huxley (HH) type ion chan...

To understand the proximate and ultimate causes that shape acoustic communication in animals, objective characterizations of the vocal repertoire of a given species are critical, as they provide the foundation for comparative analyses among individuals, populations and taxa. Progress in this field has been hampered by a lack of standard in methodol...

Neurons in many brain areas can develop pronounced depolarized state of membrane potential (up state) in addition to the normal hyperpolarized down state near the resting potential. The influence of the up state on signal encoding, however, is not well investigated. Here we construct a one-dimensional bistable neuron model and calculate the linear...

Significance Ca ²⁺ ions serve as a key cellular signal and are tightly controlled. One mechanism to limit free Ca ²⁺ ions is buffering by Ca ²⁺ -binding proteins, which are strongly expressed in sensory hair cells of the ear. Here we studied how genetic disruption of the Ca ²⁺ -binding proteins parvalbumin-α, calbindin-D28k, and calretinin affects...

Acknowledgements Baranauskas, G., David, Y., and Fleidervish, I. A. (2013). Spatial mismatch between the Na+ flux and spike initiation in axon initial segment. Proc. Natl. Acad. Sci. doi:10.1073/pnas.1215125110. Fourcaud-Trocme, N., Hansel, D., van Vreeswijk, C., and Brunel, N. (2003). How Spike Generation Mechanisms Determine the Neuronal Response...

The mechanisms underlying the large amplitudes and heterogeneity of excitatory postsynaptic currents (EPSCs) at inner hair cell (IHC) ribbon synapses are unknown. Based on electrophysiology, electron and superresolution light microscopy, and modeling, we propose that uniquantal exocytosis shaped by a dynamic fusion pore is a candidate neurotransmit...

The majority of membrane and secreted proteins, including many developmentally important signalling proteins, receptors and adhesion molecules, are cotranslationally N-glycosylated in the endoplasmic reticulum. The structure of the N-glycan is invariant for all substrates and conserved in eukaryotes. Correspondingly, the enzymes are conserved, whic...

Cortical neurons operate within recurrent neuronal circuits. Dissecting their operation is key to understanding information processing in the cortex and requires transparent and adequate dynamical models of circuit function. Convergent evidence from experimental and theoretical studies indicates that strong feedback inhibition shapes the operating...

Cochlear inner hair cells (IHCs) develop from pre-sensory pacemaker to sound transducer. Here, we report that this involves changes in structure and function of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around hearing onset in mice. As synapses matured they changed from holding several small presynaptic active zones (AZs)...

It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglio...

Purpose: Vision restoration training (VRT) in hemianopia patients leads to visual field enlargements, but the mechanisms of this vision restoration are not known. To investigate the role of residual vision in recovery, we studied topographic features of visual field charts and determined residual functions in local regions and their immediate surr...

Synchronized bursting is found in many brain areas and has also been implicated in the pathophysiology of neuropsychiatric disorders such as epilepsy, Parkinson's disease, and schizophrenia. Despite extensive studies of network burst synchronization, it is insufficiently understood how this type of network wide synchronization can be strengthened,...

The axon initial segment (AIS) controls the transformation of dendrosomatic synaptic input into spike output and the backpropagation of action potentials into the dendrites due to its lower spike initiation threshold. Channel density and kinetics can both contribute to this low threshold. However, the nature of such threshold differences is unknown...

Heterogeneity of neuronal responses is abundant in sensory systems. For example, spiral ganglion neurons (SGN), which are postsynaptic to mechanosensory inner hair cells (IHCs), show high variability in spontaneous and sound-driven discharge [1]. Recent experimental evidence implicates heterogeneity of the molecular organization of the IHC presynap...

The prevailing explanation for the irregularity of spike sequences in the cerebral cortex is a dynamic balance of excitatory and inhibitory synaptic inputs-the socalled balanced state [1]. Nevertheless its statistical properties are well described by a mean field theory that is independent of the single neuron dynamics, its dynamics is far from bei...

Dynamic instabilities have been offered as an explanation for how the olfactory bulb can separate its inputs[1]. However, models that can flexibly adjust both to separate and categorize inputs based on relevance are lacking. Dynamic stability of networks with linear coupling is determined exclusively by the Lyapunov spectrum, while nonlinear 'spike...

It has been argued that the emergence of roughly periodic orientation preference maps (OPMs) in the primary visual cortex (V1) of carnivores and primates can be explained by a so-called statistical connectivity model. This model assumes that input to V1 neurons is dominated by feed-forward projections originating from a small set of retinal ganglio...

Central neurons operate in a regime of constantly fluctuating conductances, induced by thousands of presynaptic cells. Channelrhodopsins have been almost exclusively used to imprint a fixed spike pattern by sequences of brief depolarizations. Here we introduce continuous dynamic photostimulation (CoDyPs), a novel approach to mimic in-vivo like inpu...

Dynamic oscillatory coherence is believed to play a central role in flexible communication between brain circuits. To test this communication-through-coherence hypothesis, experimental protocols that allow a reliable control of phase-relations between neuronal populations are needed. In this modeling study, we explore the potential of closed-loop o...

The abilities of neuronal populations to encode rapidly varying stimuli and respond quickly to abrupt input changes are crucial for basic neuronal computations, such as coincidence detection, grouping by synchrony, and spike-timing-dependent plasticity, as well as for the processing speed of neuronal networks. Theoretical analyses have linked these...

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specif...

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractabl...