Figure 3. The microcircuit response to peptidergic neuron activity is not necessarily mimicked by bath application of that neuropeptide.

a| This part shows schematic extracellular recordings of identified neurons in the crab Cancer borealis stomatogastric ganglion (STG), which are active during the gastric mill rhythm (LG and DG neurons), pyloric rhythm (PD neuron) or both rhythms (IC and VD neurons). In the isolated crab STG, bath-applied proctolin (far left set of responses) selectively excites the pyloric rhythm^100,102. This action mimics the response to activation of only one (modulatory proctolin neuron (MPN)) of the three proctolinergic projection neurons that innervate the STG (MPN, modulatory commissural neuron 1 (MCN1) and MCN7), even though MPN also contains a small-molecule co-transmitter (GABA)^102,105. As indicated, MPN also inhibits two projection neurons (MCN1 and commissural projection neuron 2 (CPN2)) by releasing GABA from a separate axon projecting to a separate location (commissural ganglion (CoG))^130,140. The other two proctolinergic projection neurons (MCN1 and MCN7) also influence STG microcircuit activity but elicit activity patterns from the circuit neurons that are distinct from proctolin bath application^104,105. MCN1-released C. borealis tachykinin-related peptide Ia (CabTRP Ia) and GABA are pivotal for MCN1 activation of the gastric mill rhythm, whereas its release of CabTRP Ia and proctolin dominates its excitation of the pyloric rhythm (see part b). The MCN7 actions on these rhythms result partly from proctolin and probably also from one or more yet-to-be-identified co-transmitters (indicated by ‘?’). In the figure, pyloric rhythm activity is shown in red; gastric mill rhythm activity is shown in blue; gastropyloric activity is shown in purple. b | In the crab STG, MCN1 innervates all pyloric, gastropyloric and gastric mill neurons. The figure shows a representation of responsiveness of each STG circuit neuron to the MCN1-released co-transmitters proctolin (light green), CabTRP Ia (dark green) and GABA (dark grey)^116,117. Examples of convergent peptide co-transmitter action (proctolin and CabTRP Ia), selective peptide co-transmitter action (CabTRP Ia) and selective GABA action are shown. In some cases, the STG neuron only responds to the indicated co-transmitter (or co-transmitters) (for example, Int1). In other cases, the STG neuron does respond to an additional co-transmitter but not when it is released from MCN1 (for example, LG responds to applied GABA but not GABA released from MCN1). No information is available regarding whether these co-transmitters are colocalized to all MCN1 terminals or are localized to separate terminals for their release. Part a is adapted with permission from REF.¹¹, Elsevier.