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Jonas, P.

Publications and source records attributed to Jonas, P..

3 recordsLinked to original sources

MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo

To understand the mechanisms of information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and the interrelation between these two forms of activity in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in awake, behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events. Here, we developed a new method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. First, experts were asked to manually score short epochs of data. Second, the algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Third, scored and unscored data were processed with the optimal filter, and events were detected as peaks above threshold. Finally, the area under the curve (AUC) of the receiver operating characteristics (ROC) curve was used to quantify accuracy and efficiency of detection. Additionally, cross-validation was performed to exclude overfitting of the scored data, a potential concern with machine-learning approaches. We then challenged the new detection method with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. When benchmarked using a (1-AUC)-1 metric, MOD outperformed previous methods (template-fit and deconvolution) by a factor of up to 3. Thus, MOD may become an important tool for large-scale analysis of synaptic activity in vivo and in vitro. HighlightsO_LIA new method for detection of synaptic events, termed MOD, is described C_LIO_LIThe method combines the concepts of supervised machine learning and optimal filtering C_LIO_LIThe method is useful for analysis of both in vitro and in vivo data sets C_LIO_LIMOD outperforms previously published methods for synaptic event detection by a factor of up to 3 C_LI

neuroscience

GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals

The connection from medial habenula (MHb) to interpeduncular nucleus is critical for aversion- and addiction-related behaviors. This pathway is unique in selective expression of R-type voltage-gated Ca2+ channels (Cav2.3) in its terminals, and robust potentiation of release via presynaptic GABAB receptors (GBRs). To understand the mechanism underlying this peculiar GBR effect, we examined the presynaptic localization and function of Cav2.3, GBR, and its auxiliary subunits, K+-channel tetramerization domain-containing (KCTD) proteins. We found selective co-expression of KCTD12b and Cav2.3 at the presynaptic active zone. GBR-mediated potentiation remained intact in KCTD12b KO mice but lasted significantly shorter. This impairment was associated with increased release and an insertion of KCTD8 into the active zone. In heterologous cells, we found direct binding of KCTD8 and KCTD12b to Cav2.3, and potentiation of Cav2.3 currents by KCTD8. The unexpected interaction of Cav2.3 with KCTDs therefore provides a means to scale synaptic strength independent of GBR activation.

neuroscience

Fast signaling and focal connectivity of PV+ interneurons ensure efficient patternseparation by lateral inhibition in a full-scale dentate gyrus network model

Pattern separation is a fundamental brain computation that converts small differences in synaptic input patterns into large differences in action potential (AP) output patterns. Pattern separation plays a key role in the dentate gyrus, enabling the efficient storage and recall of memories in downstream hippocampal CA3 networks. Several mechanisms for pattern separation have been proposed, including expansion of coding space, sparsification of neuronal activity, and simple thresholding mechanisms. Alternatively, a winner-takes-all mechanism, in which the most excited cells inhibit all less-excited cells by lateral inhibition, might be involved. Although such a mechanism is computationally powerful, it remains unclear whether it operates in biological networks. Here, we develop a full-scale network model of the dentate gyrus, comprised of granule cells (GCs) and parvalbumin+ (PV+) inhibitory interneurons, based on experimentally determined biophysical cellular properties and synaptic connectivity rules. Our results demonstrate that a biologically realistic principal neuron-interneuron (PN-IN) network model is a highly efficient pattern separator. Mechanistic dissection in the model revealed that a winner-takes-all mechanism by lateral inhibition plays a crucial role in pattern separation. Furthermore, both fast signaling properties of PV+ interneurons and focal GC-interneuron connectivity are essential for efficient pattern separation. Thus, PV+ interneurons are not only involved in basic microcircuit functions, but also contribute to higher-order computations in neuronal networks, such as pattern separation.

neuroscience