Similarities and differences in circuit responses to applied Gly¹-SIFamide and peptidergic (Gly¹-SIFamide) neuron stimulation

Abstract

Microcircuit modulation by peptides is well established, but the cellular/synaptic mechanisms whereby identified neurons with identified peptide transmitters modulate microcircuits remain unknown for most systems. Here, we describe the distribution of GYRKPPFNGSIFamide (Gly1-SIFamide) immunoreactivity (Gly1-SIFamide-IR) in the stomatogastric nervous system (STNS) of the crab Cancer borealis and the Gly1-SIFamide actions on the two feeding-related circuits in the stomatogastric ganglion (STG). Gly1-SIFamide-IR localized to somata in the paired commissural ganglia (CoGs), two axons in the nerves connecting each CoG with the STG, and the CoG and STG neuropil. We identified one Gly1-SIFamide-IR projection neuron innervating the STG as the previously identified modulatory commissural neuron 5 (MCN5). Brief (~10 s) MCN5 stimulation excites some pyloric circuit neurons. We now find that bath applying Gly1-SIFamide to the isolated STG also enhanced pyloric rhythm activity and activated an imperfectly coordinated gastric mill rhythm that included unusually prolonged bursts in two circuit neurons [inferior cardiac (IC), lateral posterior gastric (LPG)]. Furthermore, longer duration (>30 s) MCN5 stimulation activated a Gly1-SIFamide-like gastric mill rhythm, including prolonged IC and LPG bursting. The prolonged LPG bursting decreased the coincidence of its activity with neurons to which it is electrically coupled. We also identified local circuit feedback onto the MCN5 axon terminals, which may contribute to some distinctions between the responses to MCN5 stimulation and Gly1-SIFamide application. Thus, MCN5 adds to the few identified projection neurons that modulate a well-defined circuit at least partly via an identified neuropeptide transmitter and provides an opportunity to study peptide regulation of electrical coupled neurons in a functional context. NEW & NOTEWORTHY Limited insight exists regarding how identified peptidergic neurons modulate microcircuits. We show that the modulatory projection neuron modulatory commissural neuron 5 (MCN5) is peptidergic, containing Gly1-SIFamide. MCN5 and Gly1-SIFamide elicit similar output from two well-defined motor circuits. Their distinct actions may result partly from circuit feedback onto the MCN5 axon terminals. Their similar actions include eliciting divergent activity patterns in normally coactive, electrically coupled neurons, providing an opportunity to examine peptide modulation of electrically coupled neurons in a functional context.

Coupling between fast and slow oscillator circuits inCancer borealisis temperature compensated

“…3–figure supplement 1c ). Because there are ten known processes of gastric mill rhythm generation and all but two are distinct from one another (Heinzel et al, 1993; Coleman and Nusbaum, 1994; Norris et al, 1994, 1996; Weimann et al, 1997; Blitz et al, 1999; Christie et al, 2004; Saideman et al, 2007a; Saideman et al, 2007b; White and Nusbaum, 2011; Dickinson et al, 2015; Blitz et al, 2019), similarities between spontaneous and evoked gastric mill rhythms within a preparation suggested that these rhythms are driven by similar processes.…”

“…Coupling between these circuits coordinates the timing of chewing and filtering enabling proper flow of food through the mid-gut (Meyrand et al, 1994; Diehl et al, 2013). Furthermore, a subset of STG neurons participates in both rhythms, and therefore coupling between the pyloric and gastric mill circuits enables neurons with dual functions to maintain their appropriate participation in both rhythms (Weimann et al, 1991; Weimann and Marder, 1994; Gutierrez et al, 2013; Blitz et al, 2019).…”

“…The observed irregularity could be due to weak activation of one or more descending pathways and is likely to be different across preparations, and potentially across temperatures. There are many different processes that drive gastric mill rhythms including release of hormonal peptides such as crustacean cardioactive peptide (CCAP) (Weimann et al, 1997), FLRFamides (Heinzel et al, 1993; Weimann et al, 1993; Christie et al, 2004), pyrokinins (Saideman et al, 2007b; Dickinson et al, 2015), and Gly 1 -SIFamide (Blitz et al, 2019). Synaptically released peptides C. borealis tachykinin related peptide (CabTRP Ia) (Blitz et al, 1999; Wood et al, 2000) and C. borealis pyrokinin peptide I & II (CabPK) (Saideman et al, 2007a; Saideman et al, 2007b) generate similar gastric mill rhythms, while proctolin (Blitz et al, 1999; Stein et al, 2007) excites all gastric mill motor neurons.…”

Degenerate circuits use distinct mechanisms to respond similarly to the same perturbation

“…Such an occlusion might have occurred in some preparations because the same STG neurons in different individuals express a different maximal conductance for each of its currents (Schulz et al, 2006;Schulz et al, 2007), a feature also recognized in other systems (Luo et al, 1999;Kamme et al, 2003;Cristobal et al, 2005;Swensen and Bean, 2005;Tietjen et al, 2005). This individual variation can result in the same modulatory action having a different impact on circuit output in different preparations (Weimann et al, 1997;Schulz et al, 2006;Spitzer et al, 2008;Gabriel et al, 2009;Grashow et al, 2009;Sakurai and Katz, 2009;Grashow et al, 2010;Marder et al, 2015;Blitz et al, 2019). An occlusion effect would be less likely to occur during the MCN1rhythm, despite the fact that MCN1-released CabTRP Ia also activates I MI in LG, because MCN1-activated I MI amplitude declines during the protraction phase, whereas CCAP-activated I MI amplitude persists (DeLong et al, 2009b).…”

“…There are at least several different versions of the gastric mill rhythm in C. borealis (Blitz et al, 1999;Blitz et al, 2004;Blitz et al, 2008;White and Nusbaum, 2011;Blitz et al, 2019). Additionally, there is gastric mill circuit degeneracy, as the gastric mill rhythms driven by stimulating modulatory commissural neuron 1 (MCN1) and bathapplying CabPK (C. borealis pyrokinin) peptide are comparable, despite being generated by distinct cellular and synaptic mechanisms Saideman et al, 2007a;Stein et al, 2007;Rodriguez et al, 2013).…”