Generating Motor Rhythms through Recurrent Feedback Circuitry

Reed College, Portland OR

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Circuits that underlie neural rhythms in the nervous system are ubiquitous, and disruptions of normal rhythms are a source of neurological disorders. The overarching goal of this work is to discover novel mechanisms that underlie rhythm generation, potentially leading to novel treatments. Many rhythmic behaviors are generated by central pattern generators (CPGs), which are powerful model systems for understanding general principles of nervous system function. Because CPGs can function autonomously-generating rhythmic output without rhythmic inputs-they can be studied in vitro, thus making them experimentally very tractable. Our research investigates a hindbrain CPG that generates vocal rhythms in the frog, Xenopus laevis. This CPG generates robust, largely normal motor rhythms in vitro. Although vertebrate CPGs are thought to operate primarily in a top-down manner, in which premotor circuits faithfully drive motor output, recent data in this system suggest that bottom-up signaling, from motor to premotor neurons, is required for normal activity. This proposal has two specific aims: 1) we will identify the neurons and synapses that convey the feedback signal between the motor neurons and premotor neurons, and 2) we will assess the role that feedback circuit components play in promoting normal rhythm generation. To achieve these aims, we will use whole-cell and population-level recordings to determine how cells in the circuit are connected, how they function during normal circuit activity, and what functional consequences arise when connections are disrupted. Given that vertebrate hindbrains are highly conserved, research into the structures and mechanisms of this feedback circuit may promote the discovery and understanding of homologous brainstem networks in other species, including humans.