Multiple intrinsic membrane properties are modulated in a switch from single- to dual-network activity

Abstract

Neural network flexibility includes changes in neuronal participation between networks, such as the switching of neurons between single- and dual-network activity. We previously identified a neuron that is recruited to burst in time with an additional network via modulation of its intrinsic membrane properties, instead of being recruited synaptically into the second network. However, the modulated intrinsic properties were not determined. Here, we use small networks in the Jonah crab (Cancer borealis) stomatogastric nervous system (STNS) to examine modulation of intrinsic properties underlying neuropeptide- (Gly1-SIFamide) elicited neuronal switching. The LPG neuron switches from exclusive participation in the fast pyloric (~1 Hz) network, due to electrical coupling, to dual-network activity which includes periodic escapes from the fast rhythm via intrinsically-generated oscillations at the slower gastric mill network frequency (~0.1 Hz). We isolated LPG from both networks using pharmacology and hyperpolarizing current injection. Gly1-SIFamide increased LPG intrinsic excitability and rebound from inhibition, and decreased spike frequency adaptation, which can all contribute to intrinsic bursting. Using ion substitution and channel blockers, we found that a hyperpolarization-activated current, a persistent sodium current, and a calcium or calcium-related current(s) appear to be primary contributors to Gly1-SIFamide-elicited LPG intrinsic bursting. However, this intrinsic bursting was more sensitive to blocking currents when LPG received rhythmic electrical coupling input from the fast network than in the isolated condition. Overall, a switch from single- to dual-network activity can involve modulation of multiple intrinsic properties, while synaptic input from a second network can shape the contributions of these properties.

Switching Neuron Contributions to Second Network Activity

“…When LPG is isolated from pyloric and gastric mill inputs via hyperpolarization of the two PD neurons and application of picrotoxin (PTX, 10 µM), respectively, LPG generates slow, gastric mill-timed bursting independently due to Gly 1 -SIFamide modulation of LPG intrinsic properties (Fig. 1C, right) (17, 23). This mechanism of recruitment differs from other examples, in which modulation of synapses recruits a switching neuron into another network (10, 12, 13, 48).…”

“…Middle , Bath application of MCN5 neuropeptide Gly 1 -SIFamide increases pyloric frequency (increased PD burst frequency), activates the gastric mill rhythm ( mvn [IC], lgn [LG], dgn [DG]), and switches LPG into dual pyloric plus gastric mill-timed bursting. Right , In Gly 1 -SIFamide, when the LPG neuron is isolated from pyloric-timed input (PDs OFF) and gastric mill-timed input (PTX to block glutamatergic inhibition), LPG generates gastric mill-timed bursting intrinsically (17,23). Ganglia: CoG, commissural ganglion; OG, oesophageal ganglion; STG, stomatogastric ganglion.…”

“…In most examples with identified cellular-level mechanisms, switching neurons are recruited into another network via modulation of inter-network synapses (10, 12, 14), and passively follow this input, without contributing to network output, such as rhythm frequency or network neuron coordination. However, neurons may also be recruited into a second network via modulation of intrinsic properties (15, 17, 22, 23). Here we ask whether a switching neuron has an active role in a novel network when the recruitment mechanism is intrinsic to the switching neuron.…”

“…During the MCN5/Gly 1 -SIFamide-elicited gastric mill rhythm, LPG is coordinated with the lateral gastric (LG), inferior cardiac (IC), and dorsal gastric (DG) network neurons (17, 36). While LPG slow bursting occurs via Gly 1 -SIFamide modulation of LPG intrinsic properties (17, 23), how LPG is incorporated into the gastric mill network, and whether it contributes to rhythm and/or pattern generation is unknown. We hypothesized that LPG actively contributes to rhythm and pattern generation of the Gly 1 -SIFamide gastric mill rhythm.…”

Neural circuit regulation by identified modulatory projection neurons

“…Neuropeptide and small molecule co-neurotransmitter actions range from varying degrees of convergence, to complementary, to entirely divergent (Thirumalai and Marder, 2002;Nusbaum et al, 2017;Nässel, 2018;Florman and Alkema, 2022). In the crab STNS, a modulatory PN (MCN5) switches the CPG neuron LPG from pyloric-only network participation to dual-network (pyloric plus gastric mill) activity via its neuropeptide Gly 1 -SIFamide (Figure 1B; Fahoum and Blitz, 2021;Snyder and Blitz, 2022). However, bath applied Gly 1 -SIFamide excites the pyloric CPG neuron LP, which inhibits LPG and prevents it from fully expressing dual-network activity.…”