Coordination of distinct but interacting rhythmic motor programs by a modulatory projection neuron using different co-transmitters in different ganglia

Abstract

SUMMARYWhile many neurons are known to contain multiple neurotransmitters, the specific roles played by each co-transmitter within a neuron are often poorly understood. Here, we investigated the roles of the co-transmitters of the pyloric suppressor (PS) neurons, which are located in the stomatogastric nervous system (STNS) of the lobster Homarus americanus. The PS neurons are known to contain histamine; using RT-PCR, we identified a second co-transmitter as the FMRFamide-like peptide crustacean myosuppressin (Crust-MS). The modulatory effects of Crust-MS application on the gastric mill and pyloric patterns, generated in the stomatogastric ganglion (STG), closely resembled those recorded following extracellular PS neuron stimulation. To determine whether histamine plays a role in mediating the effects of the PS neurons in the STG, we bath-applied histamine receptor antagonists to the ganglion. In the presence of the antagonists, the histamine response was blocked, but Crust-MS application and PS stimulation continued to modulate the gastric and pyloric patterns, suggesting that PS effects in the STG are mediated largely by Crust-MS. PS neuron stimulation also excited the oesophageal rhythm, produced in the commissural ganglia (CoGs) of the STNS. Application of histamine, but not Crust-MS, to the CoGs mimicked this effect. Histamine receptor antagonists blocked the ability of both histamine and PS stimulation to excite the oesophageal rhythm, providing strong evidence that the PS neurons use histamine in the CoGs to exert their effects. Overall, our data suggest that the PS neurons differentially utilize their cotransmitters in spatially distinct locations to coordinate the activity of three independent networks.

Functional consequences of neuropeptide and small-molecule co-transmission

“…This situation precludes a first-order determination of the circuit response by directly applying the co-transmitters to the system. There are several examples of divergent co-transmission influence among the identified neurons modulating the feeding-related microcircuits in the decapod crustacean STG 59,102,103,117,128–132 (FIG. 2).…”

“…MCN1 and CPN2 are both proctolin responsive, but not as a result of MPN stimulation 130 . There is a similar, functionally and spatially separate action of histamine and its peptide co-transmitter in the inferior ventricular neuron (IVN)/pyloric suppressor (PS) projection neuron in the crab (IVN) and lobster (PS) stomatogastric system (see below) 131,132 .…”

“…With respect to co-transmission, two identified projection neuron pairs are well studied across species. These include MPN in C. borealis and GABA neuron 1/2 (GN1/2) in the lobster Homarus gammarus , and IVN in C. borealis and PS in H. americanus and H. gammarus 102,103,131,132,148 .…”

Dual-transmitter neurons: functional implications of co-release and co-transmission

“…A consideration of all these parameters is necessary to understand how dual-transmitter neurons alter the computational capabilities of neuronal circuits. Of note, the functional importance of co-transmission has been better described in select invertebrate systems, where each transmitter can differentially enhance the ability of the circuit to participate in multiple computational tasks [21–24]. Here we focus on recent studies of dual-transmitter neurons, including the mechanisms governing the release of multiple neurotransmitters, and the functional importance of co-transmission and co-release on circuit function in the mammalian CNS.…”

The complexity of small circuits: the stomatogastric nervous system

“…Many neuropeptides exist as co-transmitters in projection neurons, which in effect modify their actions. The spatial pattern of release may also matter, as co-transmitters can be released differentially into different target areas [36,37]. …”