Neuromodulatory Control of Switching between Single and Dual Oscillatory Network States

Miami University, Oxford OH

Investigators

Abstract

Networks of neurons are important for rhythmic behaviors such as walking, breathing, and chewing, as well as cognitive processes such as learning and memory. Flexibility of these rhythmic networks is essential for organisms to alter their behavioral output to meet changing demands. An important aspect of network flexibility is that neurons can rapidly switch their participation between networks. Modulatory inputs that project to rhythmic networks can induce neuronal switching through the release of chemical messengers. These chemical messengers alter network activity through their modulatory actions on the properties of neurons and on the synaptic connections between neurons. Determining how individual modulatory actions combine to elicit switching is a major challenge in the field of neuroscience. Small well-defined networks are instrumental in bridging the gap between cellular-level actions and whole network output. In particular, the crustacean stomatogastric nervous system (STNS) provides access to all network components as well as modulatory inputs to networks, and enables manipulation of individual neuronal properties and synaptic connections. This proposal uses the STNS to identify fundamental cellular mechanisms by which modulatory inputs switch neuronal participation between rhythmic networks. This includes the use of hybrid biological-computational networks to dissect the contributions of individual modulatory actions. This project also advances scientific discovery and learning for graduate and undergraduate students through training in the research lab of the principal investigator and in advanced lab-based courses. Underrepresented groups continue to be incorporated into the lab's research through partnerships with university and elementary school level STEM minority participation programs. Interestingly, neuronal switching can include neurons that switch between single and dual network activity. This switching can result in a single neuron expressing two activity patterns at two different frequencies. There is some evidence that modulatory inputs can elicit switching through their actions on synapses and neuronal properties. However, the complex interplay of electrical coupling, chemical synapses, and neuronal membrane properties has limited research at the network level. An identified modulatory input in the STNS causes a neuron to partially decouple from its electrically coupled partners in one network and simultaneously participate in a second network. The objectives of this proposal are to determine how modulatory actions, individually and collectively, regulate switching between a single and a dual network state. These objectives are achieved using a combination of electrophysiological and computational approaches, including hybrid networks in which biological and model neurons are coupled with the dynamic clamp technique. This project aims to identify novel mechanisms by which modulatory actions enable a neuron to become an active contributor to: 1) rhythm generation for two rhythms simultaneously, despite their occurrence at different frequencies, and 2) coordination among different network neurons. Determining these mechanisms will provide new insights into how electrical and chemical synapses can interact with neuronal membrane properties to regulate participation between networks. Increased understanding of how electrical coupling interacts with other network properties also provides a framework for future biological and computational studies in other rhythmic neural networks including those in larger, less accessible systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.