Researchers have long speculated that one subset of GABAergic interneurons might regulate movement by controlling the strength of sensory feedback signals from muscles. "These particular neurons are known to work presynaptically, by forming direct connections with the terminals of sensory neurons and suppressing the release of sensory neurotransmitter," said Dr. Fink. For technical reasons, the function of these interneurons, if any, in motor behavior has remained elusive.
Dr. Fink and his colleagues identified a way to access this subset of interneurons genetically in mice and then devised approaches to manipulate their function in a selective manner. In one experiment, they activated presynaptic inhibitory interneurons optogenetically, decreasing the strength of sensory-motor transmission. They also ablated these interneurons by making them selectively sensitive to a lethal toxin, abolishing their control over sensory feedback strength. Without sensory feedback regulation, forelimb movements were dominated by severe oscillatory tremors, drastically diminishing motor accuracy.
This finding, along with parallel modeling studies, indicates that presynaptic inhibitory neurons normally adjust the "gain" of sensory feedback at synapses with motor neurons and are therefore crucial for the smooth execution of movement. Understanding how these basic microcircuits regulate sensory input and motor output may, in the long run, provide insight into ways to combat the movement instability and tremor seen in many neurological disorders.
"These two studies shed new light on
|Contact: Karin Eskenazi|
Columbia University Medical Center