Fundamental Structure and Modulation of Neuronal Excitability: Synaptic Control of Coding, Resonance, and Network Synchronization

<jats:p>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.</jats:p>