%0 Journal Article %A Christoph Kirst %A Julian Ammer %A Felix Felmy %A Andreas Herz %A Martin Stemmler %T Fundamental Structure and Modulation of Neuronal Excitability: Synaptic Control of Coding, Resonance, and Network Synchronization %D 2015 %R 10.1101/022475 %J bioRxiv %P 022475 %X Neuronal encoding and collective network activity depend on the precise mechanism for generating action potentials. A dynamic switch in this mechanism could greatly expand the functional repertoire of neurons and circuits. Here we show that changes in neuronal biophysics control a complex, yet fundamental, sequence of dynamic transitions in neuronal excitability in which neurons switch from integrators to resonators near the spike threshold, from simple voltage dynamics to the bistable co-existence of action potentials and quiescence, and from continuous class-I to discontinuous class-II firing rate encoding. Using multiple bifurcation theory, we prove that this transition sequence is universal in conductance-based neurons. Using dynamic-clamp and pharmacology, we show experimentally that an increase in leak conductance or application of the inhibitory agonist GABA can dynamically induce these transitions in hippocampal and brainstem neurons. Our results imply that synaptic activity can flexibly control resonance, excitability and bistability of neurons. In simulated neuronal networks, we show that such synaptically induced transitions provide a mechanism for the dynamic gating of input signals and the targeted synchronization of sub-networks with a tunable number of neurons.Significance Neuronal function depends on the mechanism by which neurons transform synaptic input into action potentials (APs). It is unclear how neurons might control the AP mechanism to systematically modulate their responses to input signals or their collective behavior. Here we identify a complex, but model-independent, universal sequence of transitions in the dynamics of AP generation. Using patch-clamp recordings, we show that synaptic receptor activation can flexibly change the AP dynamics, confirming our theoretical predictions: non-resonant neurons develop a sub-threshold resonance, become bistable, and develop an abrupt jump in onset AP frequency. Our results explain how synapses or neuro-modulators could control neuronal excitability, influence information processing, and processing during collective network dynamics. %U https://www.biorxiv.org/content/biorxiv/early/2015/07/13/022475.full.pdf