Neuropeptide Modulation Enables Biphasic Internetwork Coordination via a Dual-Network Neuron

Abstract

Linked rhythmic behaviors, such as respiration/locomotion or swallowing/chewing often require coordination for proper function. Despite its prevalence, the cellular mechanisms controlling coordination of the underlying neural networks remain undetermined in most systems. We use the stomatogastric nervous system of the crabCancer borealisto investigate mechanisms of inter-network coordination, due to its small, well characterized feeding-related networks (gastric mill [chewing, ∼0.1 Hz]; pyloric [filtering food, ∼1 Hz]). Here, we investigate coordination between these networks during the Gly1-SIFamide neuropeptide modulatory state. Gly1-SIFamide activates a unique triphasic gastric mill rhythm in which the typically pyloric-only LPG neuron generates dual pyloric- plus gastric mill-timed oscillations. Additionally, the pyloric rhythm exhibits shorter cycles during gastric mill rhythm-timed LPG bursts, and longer cycles during IC, or IC plus LG gastric mill neuron bursts. Photoinactivation revealed that LPG is necessary to shorten pyloric cycle period, likely through its rectified electrical coupling to pyloric pacemaker neurons. Hyperpolarizing current injections demonstrated that although LG bursting enables IC bursts, only gastric mill rhythm bursts in IC are necessary to prolong the pyloric cycle period. Surprisingly, LPG photoinactivation also eliminated prolonged pyloric cycles, without changing IC firing frequency or gastric mill burst duration, suggesting that pyloric cycles are prolonged via IC synaptic inhibition of LPG, which indirectly slows the pyloric pacemakers via electrical coupling. Thus, the same dual-network neuron directly conveys excitation from its endogenous bursting and indirectly funnels synaptic inhibition to enable one network to alternately decrease and increase the cycle period of a related network.Significance StatementRelated rhythmic behaviors frequently exhibit coordination, yet the cellular mechanisms coordinating the underlying neural networks are not determined in most systems. We investigated coordination between two small, well-characterized crustacean feeding-associated networks during a neuropeptide-elicited modulatory state. We find that a dual fast/slow network neuron directly shortens fast network cycles during its slow, intrinsically generated bursts, likely via electrical coupling to fast network pacemakers, despite rectification favoring the opposite direction. Additionally, the fast network is indirectly prolonged during another slow-network phase, via chemical synaptic inhibition that is likely funneled through the same electrical synapse. Thus, a dual-network neuron alternately reinforces and diminishes neuropeptide actions, enabling distinct frequencies of a faster network across different phases of a related slower rhythm.