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Andreas Neef

Publications and source records attributed to Andreas Neef.

3 recordsLinked to original sources

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

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 \beta IV-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

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