Decoding cerebellar instructive signals for learning in the oculomotor system [electronic resource]

One critical challenge in neuroscience is to understand the function of neural activity in the service of behavior. This thesis investigated the neural instructive signals in support of behavioral changes, using motor learning in the VOR (vestibulo-ocular reflex). Motor learning in the VOR can be robustly induced by pairing head movements with visual image motion. This type of learning is supported by the cerebellar circuit. In particular, two types of cerebellar neurons, Purkinje cells and climbing fibers, have been shown to carry the instructive signals that may guide neural plasticity. However, there has been much debate on their exact roles in motor learning. We characterized the encoding of oculomotor responses in climbing fiber and Purkinje cell simple spike activities. Intriguingly, the effect of background stimulus on climbing fibers was modulated by target stimulus: greater target motion on the retina resulted in smaller background effect. The effects of target and background stimuli on VOR learning paralleled the effects on climbing fibers, suggested that these effects on learning were likely to be mediated by climbing fiber instructive signals. Based on these results, we designed training conditions that selectively elicited climbing fiber and Purkinje cell instructive signals. Our results indicate that neither instructive signal is necessary for motor learning in the VOR. Rather, the instructive signals carried by either the climbing fibers or Purkinje cell simple spikes may be sufficient to induce motor learning, with additive effects when both instructive signals are present during training. To extend the above correlational studies, I used electrical stimulation of the flocculus, the cerebellar region supporting VOR learning, to activate Purkinje cells directly. Preliminary results suggested direct activation of the Purkinje cell simple spike instructive signals could induce motor learning in the VOR. Although neural signals carried by Purkinje cells have been typically quantified by the firing rate, I found the temporal patterns of Purkinje cell spike trains were independently and differentially modulated from firing rate during oculomotor behaviors. Purkinje cell spike trains contain periods of highly regular firing, referred as regular spiking patterns. Regular spiking patterns carried most of the neural signals in the Purkinje cell responses to eye and head movements. Motor learning in the VOR has been traditionally assessed by measuring the average trajectory of eye movement responses to a vestibular stimulus, in the absence of any visual stimulus. I extended this traditional method by characterizing the eye movement responses to the visual-vestibular training stimuli--the functionally-relevant behavior. My results revealed that motor learning could improve either the accuracy or the variability of motor performance, depending on the exact training and testing conditions. In particular, the improvement/reduction in variability was achieved by shifting the reliance of a sensory pathway with high variability to a sensory pathway with low variability.

Keywords: Neurosciences.
Advisor: Raymond Jennifer L. primary advisor. Thesis advisor
Knudsen Eric I. advisor. Thesis advisor
Moore Tirin
Shenoy Krishna V. (Krishna Vaughn) advisor. Thesis advisor