TY - JOUR T1 - Conditioning by subthreshold synaptic input changes the characteristic firing pattern of CA3 hippocampal neurons JF - bioRxiv DO - 10.1101/084152 SP - 084152 AU - Saray Soldado-Magraner AU - Federico Brandalise AU - Suraj Honnuraiah AU - Michael Pfeiffer AU - Urs Gerber AU - Rodney Douglas Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/09/084152.abstract N2 - Neurons are typically classified according to their intrinsic firing patterns and distinctive morphological features. However, our experiments in the CA3 field of rat hippocampus in vitro revealed that discharge patterns change significantly following a short period of low frequency subthreshold stimulation of the neuron’s afferents. This effect could be reproduced by intrasomatic current pulses and was blocked by kinase inhibitors. Cluster analysis of the firing patterns before and after conditioning revealed systematic transitions towards adapting and intrinsic burst behaviours, irrespective of the initial pattern exhibited by the cell. Using a conductance-based model, we demonstrate that the observed transitions can be mediated by recruitment of calcium and M-type potassium conductances. We conclude that CA3 neurons adapt their conductance profile to the statistics of ongoing activity in their embedding circuits, making their intrinsic firing pattern not a constant signature, but rather the reflection of long-term circuit activity.Author summary Various anatomical types of neuron generate characteristic patterns of action potential discharge in response to intra-somatic injections of step currents. Together with the cell’s morphology and molecular markers, these patterns have been used to classify neuronal phenotypes. However, in this study we show that in the case of hippocampal CA3 neurons this discharge behavior is not as characteristic as generally assumed. Instead, the dynamics of a neuron’s supra-threshold output behavior may change significantly over a time scale of many minutes in response to sub-threshold input. Although this input is too small to evoke a spike response, the neurons nevertheless appear to adjust their membrane conductances by a mechanism that involves phosphorylation. Future suprathreshold step inputs will then elicit a different characteristic pattern of spikes. These results suggest that instead of being relatively static input-output devices, CA3 neurons modify their fundamental configuration of operation according to long-term statistics of the small on-going signals that they receive from other members of their embedding circuit. ER -