Neuronal Switching between Single- and Dual-Network Activity via Modulation of Intrinsic Membrane Properties

Oscillatory networks underlie rhythmic behaviors (e.g., walking, chewing) and complex behaviors (e.g., memory formation, decision-making). Flexibility of oscillatory networks includes neurons switching between single- and dual-network participation, even generating oscillations at two distinct frequencies. Modulation of synaptic strength can underlie this neuronal switching. Here we ask whether switching into dual-frequency oscillations can also result from modulation of intrinsic neuronal properties. The isolated stomatogastric nervous system of male Cancer borealis crabs contains two well-characterized rhythmic feeding-related networks (pyloric, ∼1 Hz; gastric mill, ∼0.1 Hz). The identified modulatory projection neuron MCN5 causes the pyloric-only lateral posterior gastric (LPG) neuron to switch to dual pyloric/gastric mill bursting. Bath applying the MCN5 neuropeptide transmitter Gly¹-SIFamide only partly mimics the LPG switch to dual activity because of continued LP neuron inhibition of LPG. Here, we find that MCN5 uses a cotransmitter, glutamate, to inhibit LP, unlike Gly¹-SIFamide excitation of LP. Thus, we modeled the MCN5-elicited LPG switching with Gly¹-SIFamide application and LP photoinactivation. Using hyperpolarization of pyloric pacemaker neurons and gastric mill network neurons, we found that LPG pyloric-timed oscillations require rhythmic electrical synaptic input. However, LPG gastric mill-timed oscillations do not require any pyloric/gastric mill synaptic input and are voltage-dependent. Thus, we identify modulation of intrinsic properties as an additional mechanism for switching a neuron into dual-frequency activity. Instead of synaptic modulation switching a neuron into a second network as a passive follower, modulation of intrinsic properties could enable a switching neuron to become an active contributor to rhythm generation in the second network.SIGNIFICANCE STATEMENT Neuromodulation of oscillatory networks can enable network neurons to switch from single- to dual-network participation, even when two networks oscillate at distinct frequencies. We used small, well-characterized networks to determine whether modulation of synaptic strength, an identified mechanism for switching, is necessary for dual-network recruitment. We demonstrate that rhythmic electrical synaptic input is required for continued linkage with a "home" network, whereas modulation of intrinsic properties enables a neuron to generate oscillations at a second frequency. Neuromodulator-induced switches in neuronal participation between networks occur in motor, cognitive, and sensory networks. Our study highlights the importance of considering intrinsic properties as a pivotal target for enabling parallel participation of a neuron in two oscillatory networks.