Philipp Rosenbaum, PhD
Department of Biology
(October 5, 2015)
Robustness of Circuit Output as Revealed by Neuromodulators With Converging Actions
Neurons that are active, or firing, in sequence are said to be oscillating. Oscillating neurons are important for certain rhythmic behaviors, such as walking or, in the case of the crab stomach, the grinding action of teeth to chew food. Oscillating neurons depend on carefully balanced levels of chemicals, or neuromodulators, to maintain the rhythm of firing. Dr. Rosenbaum discussed his work examining how rhythms can be maintained even in the absence of some necessary neuromodulators. His work highlights how networks can maintain balance by increasing the amounts of some neuromodulators to compensate for the loss of others.
Motor circuit output for stereotypic movements has to be robust against external and internal perturbations. Both intrinsic neuronal properties and synaptic strengths are targets of neuromodulation. In the well-studied stomatogastric nervous system (STNS) of the crab Cancer borealis, the specific motor output generated by each neuromodulator depends on the subset of neurons affected.
Here we show that the modulators oxotremorine/pilocarpine, CabTRP1a, and red pigment concentrating hormone (RPCH) still elicit a form of the pyloric rhythm in the absence of action potentials in TTX, graded synaptic inhibition maintaining the underlying slow-wave. Proctolin, crustacean cardioactive peptide (CCAP), and TNRNFLRFamide do not evoke a pyloric rhythm in TTX. Interestingly, all of these modulators activate the same ionic conductance. Oxotremorine rhythms with and without TTX have a similar period — both are faster than in the front-end on condition. The slow wave membrane potential oscillations look similar to the regular pyloric rhythm without spikes. CabTRP1a elicits a rhythm with a longer period compared to the intact STNS, becoming even slower in TTX. The shape of the slow wave looks similar to the oxotremorine waveform. RPCH elicits a pyloric rhythm with a regular pyloric frequency, but in combination with TTX a very different activity pattern emerges. In LP most of the oscillations drastically decrease in amplitude and stay in pyloric frequency, but interposed with these are large amplitude slow oscillations (25-40s). This rhythm is mainly LP driven and PD receives strong LP inhibition. In the isolated pacemaker kernel, oxotremorine oscillations still persist in the PD neuron with the same frequency, whereas oscillations in CabTRP1a are only rarely observed with reduced frequency.
Our data suggests that neuromodulator activation of the pacemaker kernel and graded synaptic inhibition can restore rhythmic activity in the absence of action potentials.