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

Abstract

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 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, due to continued LP neuron inhibition of LPG. Here, we find that MCN5 uses a co-transmitter, 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 StatementNeuromodulation of oscillatory networks can enable network neurons to switch from sing<bacle- 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, but that modulation of intrinsic properties is sufficient to switch a neuron into dual-frequency oscillations, linking it to a second network. Neuromodulator-induced switches in neuronal participation between networks occurs 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.