Abstract
All nervous systems are modulated by amines, amino acids, and peptides. In some cases, neuromodulators confer circuit stability such that nervous systems can maintain output despite exogenous perturbations. Additionally, they can drive state transitions in neurons, endowing circuits with the flexibility to quickly and dramatically alter their output. While these juxtaposing consequences of neuromodulation are generally understood, there remain open questions pertaining to the principles by which neuromodulators endow circuits with both rigidity and flexibility. In this thesis, I use the stomatogastric nervous system (STNS) of the crab Cancer borealis to investigate examples of each.\r \r In the first of these stories, I used temperature as a global perturbation to study how\r circuit performance is maintained in these poikilothermic animals. Previous work demonstrates that the pyloric rhythm can be maintained across a physiological range of temperatures, but less is known about how the gastric mill rhythm is maintained across that same range. As this latter rhythm is produced by a distinct rhythm generating circuit, it was not obvious that they would maintain rhythmicity as temperature was increased. While the pyloric and gastric mill rhythm generating circuits can independently produce rhythmic output, they are synaptically coupled and influence each other’s output. Here I show that while these circuits are independently temperature robust, so is the synaptic architecture that supports coupling which is maintained across this range of temperatures (7 – 23°C).\r \r In the second portion of my thesis, I show that neuromodulation of similar neural\r rhythms generated by distinct mechanisms can be both similar and distinct in response to imposed perturbations as a consequence of their underlying circuit differences. Of the many distinct gastric mill motor patterns produced by the STNS, the modulatory projection neuron MCN1 and C. borealis pyrokinin peptide (CabPK) rhythms are similar, albeit generated by distinct mechanisms. Application of the peptide hormone crustacean cardioactive peptide (CCAP) drove distinct changes in both rhythms by altering the state of the lateral gastric (LG) motor neuron. CCAP increased the cycle frequency of the CabPK rhythm by selectively decreasing retractor duration, allowing LG to escape from inhibition sooner. In the MCN1 generated rhythm, CCAP selectively prolonged protractor duration by increasing the LG burst duration. In contrast, stimulating a sensory neuron (GPR) in the STNS had comparable actions on the MCN1 and CabPK rhythms. In both cases, GPR inhibited the LG neuron, though not consistently via the same synaptic pathway. In the CabPK rhythm, inhibition is monosynaptic. In the MCN1 rhythm, GPR inhibition of LG is likely monosynaptic when GPR is stimulated during the LG burst phase, however when GPR is stimulated during the LG intraburst phase, GPR\r inhibits the MCN1 terminals that drive this rhythm and including LG. \r \r In the final section, I focally applied two of the GPR cotransmitters serotonin (5-HT) and\r allatostatin (AST) to the LG neuron individually in order to determine how GPR transmitters influence this neuron. While the greater aim of this study is to better understand cotransmission and how cotransmitters act together on their targets, it was necessary to begin by understanding how these modulators affect a single neuron individually. 5-HT and AST application similarly hyperpolarized the LG motor neuron. Fictive bursts driven by suprathreshold depolarizations in LG were inhibited by both modulators. Responses to 5-HT and AST became depolarizing when\r LG membrane potential was hyperpolarized.\r \r Together, the chapters of this thesis demonstrate how neuromodulation can both allow\r neuronal circuits to maintain output when exposed to global perturbations, and how\r neuromodulation can generate state switching in circuit output by altering the state of single neuron.