Synchrony in Networks of Type 2 Interneurons is More Robust to Noise with Hyperpolarizing Inhibition Compared to Shunting Inhibition in Both the Stochastic Population Oscillator and the Coupled Oscillator Regimes

Abstract

AbstractSynchronization in the gamma band (30-80 Hz) is mediated by PV+ inhibitory interneurons, and evidence is accumulating for the essential role of gamma oscillations in cognition. Oscillations can arise in inhibitory networks via synaptic interactions between individual oscillatory neurons (mean-driven) or via strong recurrent inhibition that destabilizes the stationary background firing rate in the fluctuation-driven balanced state, causing an oscillation in the population firing rate. Previous theoretical work focused on model neurons with Hodgkin’s type 1 excitability (integrators) connected by current-based synapses. Here we show that networks comprised of simple type 2 oscillators (resonators) exhibit a supercritical Hopf bifurcation between synchrony and asynchrony and a gradual transition via cycle skipping from coupled oscillators to stochastic population oscillator, as previously shown for type 1. We extended our analysis to homogeneous networks with conductance rather than current based synapses and found that networks with hyperpolarizing inhibitory synapses were more robust to noise than those with shunting synapses, both in the coupled oscillator and stochastic population oscillator regime. Assuming that reversal potentials are uniformly distributed between shunting and hyperpolarized values, as observed in one experimental study, converting synapses to purely hyperpolarizing favored synchrony in all cases, whereas conversion to purely shunting synapses made synchrony less robust except at very high conductance strengths. In mature neurons the synaptic reversal potential is controlled by chloride cotransporters that control the intracellular concentrations of chloride and bicarbonate ions, suggesting these transporters as a potential therapeutic target to enhance gamma synchrony and cognition.Significance StatementBrain rhythms in the gamma frequency band (30-80 Hz) depend on the activity of inhibitory interneurons and evidence for a causal role for gamma oscillations in cognitive functions is accumulating. Here we extend previous studies on synchronization mechanisms to interneurons that have an abrupt threshold frequency below which they cannot sustain firing. In addition to current based synapses, we examined inhibitory networks with conductance based synapses. We found that if the reversal potential for inhibition was below the average membrane potential (hyperpolarizing), synchrony was more robust to noise than if the reversal potential was very close to the average potential (shunting). These results have implications for therapies to ameliorate cognitive deficits.