Neural circuit regulation by identified modulatory projection neurons

Abstract

Rhythmic behaviors (e.g., walking, breathing, and chewing) are produced by central pattern generator (CPG) circuits. These circuits are highly dynamic due to a multitude of input they receive from hormones, sensory neurons, and modulatory projection neurons. Such inputs not only turn CPG circuits on and off, but they adjust their synaptic and cellular properties to select behaviorally relevant outputs that last from seconds to hours. Similar to the contributions of fully identified connectomes to establishing general principles of circuit function and flexibility, identified modulatory neurons have enabled key insights into neural circuit modulation. For instance, while bath-applying neuromodulators continues to be an important approach to studying neural circuit modulation, this approach does not always mimic the neural circuit response to neuronal release of the same modulator. There is additional complexity in the actions of neuronally-released modulators due to: (1) the prevalence of co-transmitters, (2) local- and long-distance feedback regulating the timing of (co-)release, and (3) differential regulation of co-transmitter release. Identifying the physiological stimuli (e.g., identified sensory neurons) that activate modulatory projection neurons has demonstrated multiple “modulatory codes” for selecting particular circuit outputs. In some cases, population coding occurs, and in others circuit output is determined by the firing pattern and rate of the modulatory projection neurons. The ability to perform electrophysiological recordings and manipulations of small populations of identified neurons at multiple levels of rhythmic motor systems remains an important approach for determining the cellular and synaptic mechanisms underlying the rapid adaptability of rhythmic neural circuits.