Nathaniel Sawtell, PhD

Unraveling the functions of neural circuits is a fundamental challenge for neuroscience.  Research in my laboratory focuses on understanding the functions of cerebellum-like sensory structures and the cerebellum in fish and mammals.  We are also interested in understanding the neural mechanisms through which past experience and sensorimotor context affect early stages of sensory processing.  Cerebellum-like structures associated with electrosensory systems in fish offer a number of advantages for linking synaptic, cellular, and circuit properties with systems level functions. First, the functional circuitry of cerebellum-like structures is relatively simple and well characterized.  Second, a plausible systems level function for cerebellum-like structures has been identified.

In vivo studies conducted in several phylogenetically distinct groups of fish have shown that cerebellum-like circuits act as an adaptive filter—learning and removing predictable features of the sensory input, for example those due to the animal's own behavior.  Adaptive filtering allows unpredictable and thus behaviorally relevant features of the sensory input to be processed more easily.  A combination of experimental and modeling studies have led to a hypothesis regarding how this adaptive filtering is implemented in cerebellum-like circuits.  Key ingredients include: (1) principal neurons that integrate peripheral electrosensory input with a diverse array of sensory and motor information conveyed by parallel fibers and (2) anti-Hebbian spike timing-dependent plasticity at parallel fiber synapses onto principal cells.  One goal of research in the lab is to deepen and extend our understanding of the cellular and circuit mechanisms underlying the generation and use of sensory predictions in the electrosensory lobe of weakly electric mormyrid fish.

Predicting sensory events is of general importance both for sensory processing and motor control.  Intriguingly, several lines of evidence suggest that the mammalian cerebellum itself is involved in generating such predictions.  A second focus of our research is to extend studies of sensory predictions in fish to other cerebellum-like structures and to the cerebellum itself.  Initial studies will include tests of the adaptive filter hypothesis in the mammalian dorsal cochlear nucleus and investigations of regions of the mormyrid cerebellum closely associated with electrosensory processing.