arXiv subjects

Andreas Neef

Publications and source records attributed to Andreas Neef.

4 recordsLinked to original sources

arXiv2026

Synchronized Hearts, Desynchronized Brains: A Nonlinear Dynamics Perspective for Function and Failure

Both the heart and the brain are built from electrically excitable cells, yet the emergent dynamics of these organs could not differ more. In the myocardium, a coherent traveling wave of action potentials ensures coordinated contraction; in the cerebral cortex, distributed, irregular spiking underlies efficient information processing and the generation of behavior. Here, we illuminate the principles that underlie the emergence of such distinct nonlinear dynamics using concepts from complex systems. We trace these principles across scales from ion channels and cellular action potential generation, through cellular coupling mechanisms and network architecture, to organ level dynamics and clinical phenotypes. Designed to support either synchronized waves or desynchronized information processing, the heart and the brain can thus be understood as operating on opposite sides of a synchronization phase transition. Crossing this transition implies pathological dynamics in both organs: Loss of synchrony in the heart produces arrhythmia; excess synchrony in the brain leads to epileptic seizures. We discuss how adaptation mechanisms, including plasticity, modulation, remodeling, and learning, maintain the appropriate level of (de)synchronization. Overall, we provide a unified excitable-system perspective, together with an educational notebook, to foster cross-disciplinary insights into cardiac and neural function and pathology.

q-bio.NC↗

arXiv2018

An axon initial segment is required for temporal precision in action potential encoding by neuronal populations

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 confers are not clear. Using a mutation of the AIS cytoskeletal protein βIV-spectrin, we here establish an in vitro model of neurons with a perturbed AIS architecture that retains nanoscale order but loses the ability to maintain a high NaV density. Combining experiments and simulations we show that a high NaV density in the AIS is not required for axonal AP initiation; it is however crucial for a high bandwidth of information encoding and AP timing precision. Our results provide the first experimental demonstration of axonal AP initiation without high axonal channel density and suggest that increasing the bandwidth of the neuronal code and hence the computational efficiency of network function was a major benefit of the evolution of the AIS.

q-bio.NC↗

arXiv2018

Ultrafast population coding and axo-somatic compartmentalization

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 population encoding. One hypothesis proposes that the sharp action potential onset is caused by the electrotonic separation of the site of action potential initiation from the soma, and that this spatial separation also results in ultrafast population encoding. Here we examined this hypothesis by studying the linear response properties of model neurons with a defined initiation site. We find that placing the initiation site at different axonal positions has only a weak impact on the linear response function of the model. It fails to generate the ultrafast response and high bandwidth that is observed in cortical neurons. Furthermore, the high frequency regime of the linear response function of this model is insensitive to correlation times of the input current contradicting empirical evidence. When we increase the voltage sensitivity of sodium channels at the initiation site, the two empirically observed phenomena can be recovered. We provide an explanation for the dissociation of sharp action potential onset and ultrafast response. By investigating varying soma sizes, we furthermore highlight the effect of neuron morphology on the linear response. Our results show that a sharp onset of action potentials is not sufficient for the ultrafast response. In the light of recent reports of activity-dependent repositioning of the axon initial segment, our study predicts that a more distal initiation site can lead to an increased sharpness of the somatic waveform but it does not affect the linear response of a population of neurons.

q-bio.NC↗

arXiv2013

Continuous Dynamic Photostimulation - inducing in-vivo-like fluctuating conductances with Channelrhodopsins

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 input fluctuations noninvasively in cells transfected with the weakly inactivating channelrhodopsin variant ChIEF. Even during long-term experiments, cultured neurons subjected to CoDyPs generate seemingly random, but reproducible spike patterns. In voltage clamped cells CoDyPs induced highly reproducible current waveforms that could be precisely predicted from the light-conductance transfer function of ChIEF. CoDyPs can replace the conventional, flash-evoked imprinting of spike patterns in in-vivo and in-vitro studies, preserving natural activity. When combined with non-invasive spike-detection, CoDyPs allows the acquisition of order of magnitudes larger data sets than previously possible, for studies of dynamical response properties of many individual neurons.

q-bio.NC↗